Trial Outcomes & Findings for Renal, Endocrine, and Bone Changes in Response to FTC/TDF in Uninfected Young Men Who Have Sex With Men (YMSM). (NCT NCT01769469)

Results Overview

The magnitude of change in PTH will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).

Recruitment status

COMPLETED

Target enrollment

101 participants

Primary outcome timeframe

Baseline and Week (wk) 48

Results posted on

2019-03-27

Participant Flow

The research was conducted at 11 clinical sites. Accrual was open between November 2012 and December 2013.

Participant milestones

Participant milestones
Measure	Subjects Enrolled in ATN 110 or ATN 113 A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir (TDF)/emtricitabine (FTC) (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.
Overall Study STARTED	101
Overall Study COMPLETED	66
Overall Study NOT COMPLETED	35

Reasons for withdrawal

Reasons for withdrawal
Measure	Subjects Enrolled in ATN 110 or ATN 113 A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir (TDF)/emtricitabine (FTC) (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.
Overall Study Consent Withdrawn	5
Overall Study Moved Out Of Area	3
Overall Study Lost to Follow-up	17
Overall Study Prem D/C from ATN 110/113 For Any Reason	7
Overall Study Subject Confirmed HIV Positive	3

Baseline Characteristics

Subjects with available data

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=101 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.
Age, Continuous	19.62 years STANDARD_DEVIATION 1.80 • n=101 Participants
Sex/Gender, Customized Male	101 Participants n=101 Participants
Race/Ethnicity, Customized Asian/Pacific Islander	2 Participants n=101 Participants
Race/Ethnicity, Customized Black/African American	52 Participants n=101 Participants
Race/Ethnicity, Customized White	16 Participants n=101 Participants
Race/Ethnicity, Customized White/Hispanic	14 Participants n=101 Participants
Race/Ethnicity, Customized Other/Mixed Race	26 Participants n=101 Participants
Race/Ethnicity, Customized Non-Black/African American	49 Participants n=101 Participants
Race/Ethnicity, Customized Hispanic	34 Participants n=101 Participants
Race/Ethnicity, Customized Non-Hispanic	67 Participants n=101 Participants
Parathyroid hormone (PTH)	27.07 pg/mL n=100 Participants • Subjects with available data
Fibroblast growth factor 23 (FGF23)	38.78 pg/mL n=100 Participants • Subjects with available data
1,25-dihydroxy vitamin D (1,25-OHD RIA)	160.71 pmol/L n=100 Participants • Subjects with available data
Tubular reabsorption of phosphate (TRP)	91.40 % (of filtered phosphorus reabsorbed) n=101 Participants
Actual Free 123(OH)D	994.88 fmol/L n=100 Participants • Subjects with available data
Estimated glomerular filtration rate (eGFR)	127.50 mL/min/1.73^2 n=101 Participants
Serum Creatinine (SCr)	0.86 mg/dL n=101 Participants
Serum Calcium (SCa)	9.80 mg/dL n=101 Participants
Urinary Calcium/ Urinary Creatinine ratio (UCa/UCr)	0.06 ratio n=101 Participants
Serum Phosphate (SPO4)	1.16 mmol/L n=101 Participants
Urine Glucose (UGluc)	0.07 mg/dL n=101 Participants
Urine retinol binding protein to urine creatinine ratio (URBP/UCr)	7092.50 mcg/g n=100 Participants • Subjects with data available.
Urine beta-2 microglobulin (UB2MG)	170.04 ng/mL n=97 Participants • Subjects with available data
Urine protein to urine creatinine ratio (UProt/UCr)	0.05 ratio n=101 Participants
Osteocalcin (OC)	9.50 mcg/L n=100 Participants • Subjects with available data
C-telopeptide (CTX)	935.76 pg/mL n=100 Participants • Subjects with available data
Lumbar spine bone mineral density (BMD)	1.09 g/cm^2 n=101 Participants
Femoral neck bone mineral density (BMD)	1.03 g/cm^2 n=100 Participants • Subjects with available data
Total body bone mineral content (BMC)	2690.83 g n=101 Participants

PRIMARY outcome

Timeframe: Baseline and Week (wk) 48

Population: Subjects with PTH data at baseline and Week 48

The magnitude of change in PTH will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=70 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Magnitude of Change (Fold Change) in Parathyroid Hormone (PTH) From Baseline to Week 48	1.08 fold change Interval 0.61 to 2.59	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=70 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Fibroblast Growth Factor 23 (FGF23), Change From Baseline to Week 48	-1.50 pg/ML Interval -25.5 to 65.18	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

The magnitude of change in FGF23 will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=70 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Fibroblast Growth Factor 23 (FGF23), Magnitude of Fold Change	0.96 fold change Interval 0.54 to 2.47	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36 and 48

Population: Subjects with at least two measurements available for comparison

Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Fibroblast Growth Factor 23 (FGF23), Most Extreme Fold Change	1.18 fold change Interval 0.67 to 2.47	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Fibroblast Growth Factor 23 (FGF23), Time to Most Extreme Fold Change	12.00 weeks Interval 4.0 to 48.0	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=71 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: 1,25 Dihydroxy Vitamin D (1,25 OHD), Change From Baseline to Week 48	-8.61 pmol/L Interval -135.4 to 197.62	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

The magnitude of change in 1,25 OHD will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=71 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: 1,25 OHD, Magnitude of Fold Change	0.95 fold change Interval 0.42 to 2.87	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36 and 48

Population: Subjects with at least two measurements available for comparison

Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: 1,25 OHD, Most Extreme Fold Change	1.33 fold change Interval 0.74 to 3.06	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: 1,25 OHD, Time to Most Extreme Fold Change	12.00 weeks Interval 4.0 to 48.0	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=71 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Tubular Reabsorption of Phosphate (TRP), Change From Baseline to Week 48	-0.57 percentage of phosphorus reabsorbed Interval -10.8 to 10.54	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

The magnitude of change in TRP will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=71 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: TRP, Magnitude of Fold Change	0.99 fold change Interval 0.89 to 1.13	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36 and 48

Population: Subjects with at least two measurements available for comparison

Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: TRP, Most Extreme Fold Change	1.05 fold change Interval 0.97 to 1.47	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: TRP, Time to Most Extreme Fold Change	24.00 weeks Interval 4.0 to 48.0	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=70 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Glomerular Filtration Rate (GFR), Change From Baseline to Week 48	3.06 ml/min/1.73m^2 Interval -32.03 to 95.42	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

The magnitude of change in GFR will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=70 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: GFR, Magnitude of Fold Change	1.02 fold change Interval 0.76 to 1.83	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36 and 48

Population: Subjects with at least two measurements available for comparison

Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: GFR, Most Extreme Fold Change	1.10 fold change Interval 0.77 to 1.83	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: GFR, Time to Most Extreme Fold Change	24.00 weeks Interval 4.0 to 48.0	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36 and 48

Population: Subjects with at least two measurements available for comparison

Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: PTH, Most Extreme Fold Change	1.35 fold change Interval 0.59 to 2.81	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: PTH, Time to Most Extreme Fold Change	24.00 weeks Interval 4.0 to 48.0	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Serum Creatinine (SCr), Time to Most Extreme Fold Change	8.00 weeks Interval 4.0 to 48.0	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The slope from baseline to most extreme fold change can be expressed as: Slope = \[(Most extreme fold change) \* (baseline value) - (baseline value)\] / \[(Time to most extreme fold change) - (time of the baseline value)\]

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: PTH, Slope of the Curve of Baseline to Most Extreme Fold Change	0.51 (pg/mL)/ weeks Interval -8.33 to 11.43	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The slope from baseline to most extreme fold change can be expressed as: Slope = \[(Most extreme fold change) \* (baseline value) - (baseline value)\] / \[(Time to most extreme fold change) - (time of the baseline value)\]

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: FGF23, Slope of the Curve of Baseline to Most Extreme Fold Change	0.39 (pg/mL)/ weeks Interval -5.14 to 9.21	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The slope from baseline to most extreme fold change can be expressed as: Slope = \[(Most extreme fold change) \* (baseline value) - (baseline value)\] / \[(Time to most extreme fold change) - (time of the baseline value)\]

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: 1,25-OHD, Slope of the Curve of Baseline to Most Extreme Fold Change	4.27 (pmol/L)/ weeks Interval -12.84 to 32.92	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The slope from baseline to most extreme fold change can be expressed as: Slope = \[(Most extreme fold change) \* (baseline value) - (baseline value)\] / \[(Time to most extreme fold change) - (time of the baseline value)\]

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: TRP, Slope of the Curve of Baseline to Most Extreme Fold Change	0.21 (% phosphorus reabsorbed)/ weeks Interval -0.4 to 3.93	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

Serum calcium Week 48 difference from baseline

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=70 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change From Baseline to Week 48 in Serum Calcium (SCa)	-0.07 mg/dL Interval -1.28 to 1.9	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with data available for at least two time points

Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Magnitude of Most Extreme Fold Change: Serum Calcium (SCa)	1.03 fold change Interval 0.91 to 1.19	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Time to Most Extreme Fold Change: Serum Calcium (SCa)	12.00 weeks Interval 4.0 to 48.0	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The slope from baseline to most extreme fold change can be expressed as: Slope = \[(Most extreme fold change) \* (baseline value) - (baseline value)\] / \[(Time to most extreme fold change) - (time of the baseline value)\]

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Slope of the Curve of Baseline to Most Extreme Fold Change: Serum Calcium (SCa)	0.02 (mg/dL)/ weeks Interval -0.12 to 0.27	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

Urine Calcium (UCa) / Urine Creatinine (UCr) ratio Week 48 difference from baseline

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=71 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change From Baseline to Week 48 in Urine Calcium (UCa) / Urine Creatinine (UCr)	0.00 ratio Interval -0.19 to 0.3	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Magnitude of Most Extreme Fold Change: UCa/UCr Ratio	1.95 fold change Interval 0.27 to 11.03	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Time to Most Extreme Fold Change: UCa/UCr Ratio	12.00 weeks Interval 4.0 to 48.0	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The slope from baseline to most extreme fold change can be expressed as: Slope = \[(Most extreme fold change) \* (baseline value) - (baseline value)\] / \[(Time to most extreme fold change) - (time of the baseline value)\]

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Slope of the Curve of Baseline to Most Extreme Fold Change: UCa/UCr Ratio	0.00 (mg/mg)/ weeks Interval -0.01 to 0.03	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

Serum Phosphate (SPO4) Week 48 difference from baseline

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=71 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change From Baseline to Week 48 in Serum Phosphate (SPO4)	0.00 mmol/L Interval -0.67 to 0.47	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Magnitude of Most Extreme Fold Change: SPO4	1.14 fold change Interval 0.79 to 1.78	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Time to Most Extreme Fold Change: SPO4	12.00 weeks Interval 4.0 to 48.0	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The slope from baseline to most extreme fold change can be expressed as: Slope = \[(Most extreme fold change) \* (baseline value) - (baseline value)\] / \[(Time to most extreme fold change) - (time of the baseline value)\]

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Slope of the Curve of Baseline to Most Extreme Fold Change: SPO4	0.01 (mmol/L)/ weeks Interval -0.05 to 0.09	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

URBP/UCr Week 48 difference from baseline

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=69 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Change From Baseline to Week 48 in Urine Retinol Binding Protein (URBP)/ Urine Creatinine (UCr)	-601.14 mcg/g Interval -29433.03 to 42595.81	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

UB2MG Week 48 difference from baseline

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=67 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Change From Baseline to Week 48 in Urine Beta-2 Microglobulin (UB2MG)	-34.78 ng/mL Interval -1252.73 to 597.59	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

UProt/ UCr Week 48 difference from baseline

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=71 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Change From Baseline to Week 48 in Urine Protein (UProt) / Urine Creatinine (UCr)	0.00 ratio Interval -0.07 to 0.06	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

UGluc Week 48 difference from baseline

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=71 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Change From Baseline to Week 48 in Urine Glucose (UGluc)	-0.01 mg/dL Interval -0.1 to 0.11	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

SCr Week 48 difference from baseline

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=71 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Change From Baseline to Week 48 in Serum Creatinine (SCr)	-0.01 mg/dL Interval -0.12 to 0.27	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

The magnitude of change in URBP/UCr will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=69 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Magnitude of Fold Change at Week 48 in Urine Retinol Binding Protein (URBP)/ Urine Creatinine (UCr)	0.81 fold change Interval 0.0 to 11.94	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

The magnitude of change in UB2MG will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=67 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Magnitude of Fold Change at Week 48 in Urine Beta-2 Microglobulin (UB2MG)	0.72 fold change Interval 0.08 to 50.5	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

The magnitude of change in UProt/UCr will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=71 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Magnitude of Fold Change at Week 48 in Urine Protein (UProt)/ Urine Creatinine (UCr)	1.01 fold change Interval 0.43 to 2.17	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

The magnitude of change in UGluc will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=71 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Magnitude of Fold Change at Week 48 in Urine Glucose (UGluc)	0.94 fold change Interval 0.08 to 4.45	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

The magnitude of change in SCr will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=71 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Magnitude of Fold Change at Week 48 in Serum Creatinine (SCr)	0.99 fold change Interval 0.85 to 1.27	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36 and 48

Population: Subjects with at least two measurements available for comparison

Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Most Extreme Fold Change in Urine Retinol Binding Protein (URBP)/ Urine Creatinine (UCr)	1.80 fold change Interval 0.44 to 15.27	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36 and 48

Population: Subjects with at least two measurements available for comparison

Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=87 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Most Extreme Fold Change in UB2MG	2.59 fold change Interval 0.11 to 239.26	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36 and 48

Population: Subjects with at least two measurements available for comparison

Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Most Extreme Fold Change in UProt/UCr	1.36 fold change Interval 0.42 to 4.46	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36 and 48

Population: Subjects with at least two measurements available for comparison

Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Most Extreme Fold Change in UGluc	1.56 fold change Interval 0.62 to 11.34	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36 and 48

Population: Subjects with at least two measurements available for comparison

Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Most Extreme Fold Change in SCr	1.09 fold change Interval 0.89 to 1.34	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Time to Most Extreme Fold Change in Urine Retinol Binding Protein (URBP)/ Urine Creatinine (UCr)	12.00 weeks Interval 4.0 to 48.0	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=87 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Time to Most Extreme Fold Change in UB2MG	12.00 weeks Interval 4.0 to 48.0	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Time to Most Extreme Fold Change in UProt/UCr	24.00 weeks Interval 4.0 to 48.0	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Time to Most Extreme Fold Change in UGluc	24.00 weeks Interval 4.0 to 48.0	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The slope from baseline to most extreme fold change can be expressed as: Slope = \[(Most extreme fold change) \* (baseline value) - (baseline value)\] / \[(Time to most extreme fold change) - (time of the baseline value)\]

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Slope of the Curve of Baseline to Most Extreme Fold Change in Urine Retinol Binding Protein (URBP)/ Urine Creatinine (UCr)	270.70 (mcg/g)/ weeks Interval -742.0 to 6995.69	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The slope from baseline to most extreme fold change can be expressed as: Slope = \[(Most extreme fold change) \* (baseline value) - (baseline value)\] / \[(Time to most extreme fold change) - (time of the baseline value)\]

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=87 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Slope of the Curve of Baseline to Most Extreme Fold Change in UB2MG	12.45 (ng/mL)/ weeks Interval -837.01 to 297.28	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The slope from baseline to most extreme fold change can be expressed as: Slope = \[(Most extreme fold change) \* (baseline value) - (baseline value)\] / \[(Time to most extreme fold change) - (time of the baseline value)\]

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Slope of the Curve of Baseline to Most Extreme Fold Change in UProt/UCr	0.00 Weeks^-1 Interval -0.01 to 0.03	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The slope from baseline to most extreme fold change can be expressed as: Slope = \[(Most extreme fold change) \* (baseline value) - (baseline value)\] / \[(Time to most extreme fold change) - (time of the baseline value)\]

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Slope of the Curve of Baseline to Most Extreme Fold Change in UGluc	0.00 (mg/dL)/ weeks Interval -0.01 to 0.02	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The slope from baseline to most extreme fold change can be expressed as: Slope = \[(Most extreme fold change) \* (baseline value) - (baseline value)\] / \[(Time to most extreme fold change) - (time of the baseline value)\]

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=91 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Glomerular and Renal Tubular Function: Slope of the Curve of Baseline to Most Extreme Fold Change in Scr	0.01 (mg/dL)/ weeks Interval -0.03 to 0.06	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

OC Week 48 difference from baseline

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=70 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Change From Baseline to Week 48 in Osteocalcin (OC)	0.05 mcg/L Interval -6.17 to 7.77	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for baseline and Week 48

CTX Week 48 difference from baseline

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=70 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Change From Baseline to Week 48 in C-Telopeptide (CTX)	25.90 pM Interval -819.51 to 1368.54	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36 and 48

Population: Subjects with at least two measurements available for comparison

Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Most Extreme Fold Change in Osteocalcin (OC)	1.14 fold change Interval 0.67 to 1.76	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36 and 48

Population: Subjects with at least two measurements available for comparison

Most extreme fold change: This is the highest or lowest value measured as fold change from the baseline value of that variable.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Most Extreme Fold Change in C-telopeptide (CTX)	1.37 fold change Interval 0.74 to 4.05	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: OC, Time to Most Extreme Fold Change	12.00 weeks Interval 4.0 to 48.0	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The time to most extreme fold change is the study week associated with the most extreme fold change or extreme percent change from baseline.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Time to Most Extreme Fold Change in C-telopeptide (CTX)	12.00 weeks Interval 4.0 to 48.0	—

SECONDARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The slope from baseline to most extreme fold change can be expressed as: Slope = \[(Most extreme fold change) \* (baseline value) - (baseline value)\] / \[(Time to most extreme fold change) - (time of the baseline value)\]

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Slope of the Curve of Baseline to Most Extreme Fold Change in OC	0.07 (mcg/L)/ weeks Interval -0.46 to 1.19	—

SECONDARY outcome

Timeframe: Baseline, Weeks (wks) 4, 8, 12, 24, 36, and 48

Population: Subjects with at least two measurements available for comparison

The slope from baseline to most extreme fold change can be expressed as: Slope = \[(Most extreme fold change) \* (baseline value) - (baseline value)\] / \[(Time to most extreme fold change) - (time of the baseline value)\]

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=90 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Change in Renal-endocrine-bone Biochemistry and Pathophysiology: Slope of the Curve of Baseline to Most Extreme Fold Change in CTX	17.98 (pM)/ weeks Interval -64.74 to 375.51	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=23 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=19 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in PTH, by Overall Drug Exposure	-0.09 pg*wks/mL Interval -16.18 to 26.87	3.59 pg*wks/mL Interval -13.39 to 24.54

SECONDARY outcome

Timeframe: Baseline and wk 24

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=26 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=26 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in PTH, by Overall Drug Exposure	0.46 pg*wks/mL Interval -15.21 to 32.73	0.47 pg*wks/mL Interval -28.89 to 17.5

SECONDARY outcome

Timeframe: Baseline and wk 24

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=26 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=26 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in FGF23, by Overall Drug Exposure	-6.88 pg*wks/mL Interval -27.23 to 17.18	0.79 pg*wks/mL Interval -62.55 to 26.42

SECONDARY outcome

Timeframe: Baseline and wk 48

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=23 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=19 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in FGF23, by Overall Drug Exposure	1.66 pg*wks/mL Interval -23.96 to 29.5	0.60 pg*wks/mL Interval -23.57 to 24.39

SECONDARY outcome

Timeframe: Baseline and wk 24

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=27 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=26 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in 1,25 OHD, by Overall Drug Exposure	10.80 pmol*wks/L Interval -117.15 to 91.65	7.07 pmol*wks/L Interval -123.12 to 228.28

SECONDARY outcome

Timeframe: Baseline and wk 48

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=24 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=19 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in 1,25 OHD, by Overall Drug Exposure	-12.55 pmol*wks/L Interval -135.4 to 67.17	-8.60 pmol*wks/L Interval -63.87 to 197.62

SECONDARY outcome

Timeframe: Baseline and wk 24

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=26 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=26 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in Osteocalcin (OC), by Overall Drug Exposure	0.87 mcg*wks/L Interval -3.61 to 4.63	-1.03 mcg*wks/L Interval -4.87 to 5.02

SECONDARY outcome

Timeframe: Baseline and wk 48

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=23 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=19 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in Osteocalcin (OC), by Overall Drug Exposure	1.12 mcg*wks/L Interval -4.12 to 7.77	-0.10 mcg*wks/L Interval -6.17 to 3.22

SECONDARY outcome

Timeframe: Baseline and wk 24

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=26 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=26 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in CTX, by Overall Drug Exposure	105.89 pM*wks Interval -527.16 to 817.21	-25.90 pM*wks Interval -819.51 to 969.14

SECONDARY outcome

Timeframe: Baseline and wk 48

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=23 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=19 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in CTX, by Overall Drug Exposure	50.64 pM*wks Interval -646.29 to 622.69	-20.72 pM*wks Interval -819.51 to 576.65

SECONDARY outcome

Timeframe: Baseline and wk 24

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=27 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=26 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in SCr, by Overall Drug Exposure	0.02 mg*wks/dL Interval -0.09 to 0.14	0.00 mg*wks/dL Interval -0.19 to 0.13

SECONDARY outcome

Timeframe: Baseline and wk 48

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=24 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=19 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in SCr, by Overall Drug Exposure	0.01 mg*wks/dL Interval -0.12 to 0.15	-0.02 mg*wks/dL Interval -0.1 to 0.27

SECONDARY outcome

Timeframe: Baseline and wk 24

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=27 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=26 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in TRP, by Overall Drug Exposure	0.57 % of phosphorus reabsorbed*wks Interval -13.44 to 15.72	1.14 % of phosphorus reabsorbed*wks Interval -8.58 to 11.38

SECONDARY outcome

Timeframe: Baseline and wk 48

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=24 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=19 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in TRP, by Overall Drug Exposure	0.03 % of phosphorus reabsorbed*wks Interval -7.37 to 9.51	-1.28 % of phosphorus reabsorbed*wks Interval -10.43 to 5.87

SECONDARY outcome

Timeframe: Baseline and wk 24

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=27 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=26 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in UCa/UCr Ratio, by Overall Drug Exposure	0.00 ratio*weeks Interval -0.06 to 0.12	-0.01 ratio*weeks Interval -0.15 to 0.27

SECONDARY outcome

Timeframe: Baseline and wk 48

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=24 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=19 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in UCa/UCr Ratio, by Overall Drug Exposure	0.00 ratio*weeks Interval -0.06 to 0.3	0.00 ratio*weeks Interval -0.17 to 0.11

SECONDARY outcome

Timeframe: Baseline and wk 24

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=26 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=25 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in UB2MG, by Overall Drug Exposure	-7.28 ng*wks/mL Interval -852.86 to 980.03	-23.29 ng*wks/mL Interval -3716.53 to 1987.72

SECONDARY outcome

Timeframe: Baseline and wk 48

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=23 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=18 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in UB2MG, by Overall Drug Exposure	-0.21 ng*wks/mL Interval -802.31 to 594.44	-79.82 ng*wks/mL Interval -1152.17 to 393.8

SECONDARY outcome

Timeframe: Baseline and wk 24

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=27 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=26 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in UGluc, by Overall Drug Exposure	-0.02 mg*wks/dL Interval -0.07 to 0.1	0.01 mg*wks/dL Interval -0.07 to 0.18

SECONDARY outcome

Timeframe: Baseline and wk 48

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=24 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=19 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in UGluc, by Overall Drug Exposure	-0.01 mg*wks/dL Interval -0.09 to 0.06	0.02 mg*wks/dL Interval -0.09 to 0.1

SECONDARY outcome

Timeframe: Baseline and wk 24

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=26 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=24 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in URBP/UCr Ratio, by Overall Drug Exposure	-2281.71 mcg*wks/g Interval -20957.98 to 23305.58	808.53 mcg*wks/g Interval -21627.73 to 11630.96

SECONDARY outcome

Timeframe: Baseline and wk 48

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=23 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=18 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in URBP/UCr Ratio, by Overall Drug Exposure	-710.86 mcg*wks/g Interval -25872.11 to 12990.8	1606.38 mcg*wks/g Interval -29433.03 to 8572.38

SECONDARY outcome

Timeframe: Baseline and wk 24

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=26 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=26 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Percent Change From Baseline to Week 24 in Lumbar Spine BMD, by Overall Drug Exposure	-0.33 % change*wks Interval -4.62 to 4.63	0.00 % change*wks Interval -2.83 to 5.75

SECONDARY outcome

Timeframe: Baseline and wk 48

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=24 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=18 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Percent Change From Baseline to Week 48 in Lumbar Spine BMD, by Overall Drug Exposure	-0.32 % change*wks Interval -4.47 to 3.74	0.88 % change*wks Interval -2.44 to 7.98

SECONDARY outcome

Timeframe: Baseline and wk 24

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure. The time points at which data were collected were: weeks 4, 8, 12, and 24.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=26 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=26 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in Lumbar Spine BMD Z-score, by Overall Drug Exposure	-0.10 z-score Interval -0.6 to 0.3	0.00 z-score Interval -0.5 to 0.6

SECONDARY outcome

Timeframe: Baseline and wk 48

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=24 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=18 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in Lumbar Spine BMD Z-score, by Overall Drug Exposure	-0.20 z-score Interval -0.5 to 0.2	-0.10 z-score Interval -0.8 to 0.6

SECONDARY outcome

Timeframe: Baseline and wk 24

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=26 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=24 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Percent Change From Baseline to Week 24 in Femoral Neck BMD, by Overall Drug Exposure	-0.80 % change*wks Interval -7.34 to 2.31	0.62 % change*wks Interval -3.89 to 8.13

SECONDARY outcome

Timeframe: Baseline and wk 48

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=24 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=17 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Percent Change From Baseline to Week 48 in Femoral Neck BMD, by Overall Drug Exposure	-1.89 % change*wks Interval -5.09 to 4.39	1.14 % change*wks Interval -2.54 to 8.48

SECONDARY outcome

Timeframe: Baseline and wk 24

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure. The time points at which data were collected were: weeks 4, 8, 12, and 24.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=25 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=24 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 24 in Femoral Neck BMD Z-score, by Overall Drug Exposure	-0.10 z-score Interval -0.6 to 0.2	0.00 z-score Interval -0.4 to 0.4

SECONDARY outcome

Timeframe: Baseline and wk 48

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=23 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=17 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Change From Baseline to Week 48 in Femoral Neck BMD Z-score, by Overall Drug Exposure	-0.10 z-score Interval -0.5 to 0.3	0.10 z-score Interval -0.7 to 0.4

SECONDARY outcome

Timeframe: Baseline and wk 24

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, and 24.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=26 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=26 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Percent Change From Baseline to Week 24 in Total Body BMC, by Overall Drug Exposure	-0.40 % change*wks Interval -5.38 to 2.44	-0.24 % change*wks Interval -3.49 to 8.79

SECONDARY outcome

Timeframe: Baseline and wk 48

Overall drug exposure categories were determined based on the overall tertiles of mean AUC dried blood spot (DBS) Red Blood Cell (RBC) Tenofovir Diphosphate (intracellular) (TFV-DP). Comparisons were performed between the high exposure group and the low exposure group. The time points at which data were collected were: weeks 4, 8, 12, 24, 36, and 48.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=24 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group n=18 Participants Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Area Under the Drug Concentration by Time Curve (AUC): Percent Change From Baseline to Week 48 in Total Body BMC, by Overall Drug Exposure	-0.60 % change*wks Interval -7.69 to 3.08	-1.24 % change*wks Interval -3.79 to 12.21

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for Baseline and Week 48

The magnitude of change will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=70 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Magnitude of Change in Lumbar Spine BMD at Week 48	1.00 fold change Interval 0.94 to 1.08	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for Baseline and Week 48

The magnitude of change will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline). The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=68 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Magnitude of Change in Lumbar Spine BMD Z-score at Week 48	1.04 fold change Interval -0.33 to 4.5	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for Baseline and Week 48

The magnitude of change will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=69 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Magnitude of Change in Femoral Neck BMD at Week 48	1.00 fold change Interval 0.92 to 1.08	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for Baseline and Week 48

The magnitude of change will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=62 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Magnitude of Change in Femoral Neck BMD Z-score at Week 48	1.00 fold change Interval -1.0 to 2.5	—

SECONDARY outcome

Timeframe: Baseline and wk 48

Population: Subjects with data for Baseline and Week 48

The magnitude of change will be measured between Baseline and Week 48. For any given variable, at a given time point, the magnitude of change is the fold change compared to the baseline value (if multiplied by 100 would be the percent change from baseline).

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=70 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Magnitude of Change in Total Body BMC at Week 48	1.00 fold change Interval 0.92 to 1.12	—

SECONDARY outcome

Timeframe: Baseline and wk 72

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the first Extension Phase visit (BL - EPH1)

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=37 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Lumbar Spine BMD Change at EPH1 From Baseline	-0.01 g/cm^2 Interval -0.067 to 0.056	—

SECONDARY outcome

Timeframe: Baseline and wk 96

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the second Extension Phase visit (BL - EPH2)

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=40 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Lumbar Spine BMD Change at EPH2 From Baseline	-0.01 g/cm^2 Interval -0.07 to 0.06	—

SECONDARY outcome

Timeframe: Wk 48 (or last available measurement on study), Wk 72

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the first Extension Phase visit (Last - EPH1)

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=37 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Lumbar Spine BMD Change at EPH1 From Week 48 (or Last Visit on Study)	-0.01 g/cm^2 Interval -0.07 to 0.03	—

SECONDARY outcome

Timeframe: Wk 48 (or last available measurement on study), Wk 96

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the second Extension Phase visit (Last - EPH2)

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=40 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Lumbar Spine BMD Change at EPH2 From Week 48 (or Last Visit on Study)	-0.01 g/cm^2 Interval -0.09 to 0.05	—

SECONDARY outcome

Timeframe: Baseline and wk 72

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the first Extension Phase visit (BL - EPH1). The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=37 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Lumbar Spine BMD Z-score Change at EPH1 From Baseline	0.10 z-score Interval -0.6 to 1.0	—

SECONDARY outcome

Timeframe: Baseline and wk 96

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the second Extension Phase visit (BL - EPH2) The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=40 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Lumbar Spine BMD Z-score Change at EPH2 From Baseline	0.20 z-score Interval -0.6 to 0.9	—

SECONDARY outcome

Timeframe: Wk 48 (or last available measurement on study), Wk 72

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the first Extension Phase visit (Last - EPH1) The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=37 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Lumbar Spine BMD Z-score Change at EPH1 From Week 48 (or Last Visit on Study)	0.00 z-score Interval -0.5 to 0.3	—

SECONDARY outcome

Timeframe: Wk 48 (or last available measurement on study), Wk 96

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the second Extension Phase visit (Last - EPH2) The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=40 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Lumbar Spine BMD Z-score Change at EPH2 From Week 48 (or Last Visit on Study)	0.00 z-score Interval -0.5 to 0.4	—

SECONDARY outcome

Timeframe: Baseline and wk 72

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the first Extension Phase visit (BL - EPH1)

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=37 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Femoral Neck BMD Change at EPH1 From Baseline	0.01 g/cm^2 Interval -0.06 to 0.05	—

SECONDARY outcome

Timeframe: Baseline and wk 96

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the second Extension Phase visit (BL - EPH2)

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=40 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Femoral Neck BMD Change at EPH2 From Baseline	0.00 g/cm^2 Interval -0.07 to 0.1	—

SECONDARY outcome

Timeframe: Wk 48 (or last available measurement on study), Wk 72

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the first Extension Phase visit (Last- EPH1)

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=37 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Femoral Neck BMD Change at EPH1 From Week 48 (or Last Visit on Study)	0.00 g/cm^2 Interval -0.06 to 0.09	—

SECONDARY outcome

Timeframe: W 48 (or last available measurement on study), Wk 96

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the second Extension Phase visit (Last- EPH2)

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=40 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Femoral Neck BMD Change at EPH2 From Week 48 (or Last Visit on Study)	-0.01 g/cm^2 Interval -0.1 to 0.08	—

SECONDARY outcome

Timeframe: Baseline and wk 72

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the first Extension Phase visit (BL - EPH1) The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=35 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Femoral Neck BMD Z-score Change at EPH1 From Baseline	0.10 z-score Interval -0.3 to 0.7	—

SECONDARY outcome

Timeframe: Baseline, Week 96

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the second Extension Phase visit (BL - EPH2) The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=38 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Femoral Neck BMD Z-score Change at EPH2 From Baseline	0.10 z-score Interval -0.5 to 0.8	—

SECONDARY outcome

Timeframe: Week 48 (or last available measurement on study), Week 72

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the first Extension Phase visit (Last - EPH1) The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=37 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Femoral Neck BMD Z-score Change at EPH1 From Week 48 (or Last Visit on Study)	0.00 z-score Interval -0.4 to 0.7	—

SECONDARY outcome

Timeframe: Wk 48 (or last available measurement on study), Wk 96

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the second Extension Phase visit (Last - EPH2). The Z-score is the standard deviation around mean bone mineral density, adjusted for sex, age, and race/ethnicity. An average Z-score of zero would be expected in this group of healthy adolescents and young adults. An increase in Z-score would signify acceleration of accrual of bone mass, a positive outcome; a decrease in Z-score would signify either bone loss or failure to accrue the expected amount of bone mass, both of which are adverse outcomes. The Z-score is a normalized measure.

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=40 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Femoral Neck BMD Z-score Change at EPH2 From Week 48 (or Last Visit on Study)	-0.05 z-score Interval -0.6 to 0.6	—

SECONDARY outcome

Timeframe: Baseline and wk 72

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the first Extension Phase visit (BL - EPH1)

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=37 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Total Body BMC Change at EPH1 From Baseline	7.90 g Interval -105.01 to 129.0	—

SECONDARY outcome

Timeframe: Baseline and wk 96

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the Baseline measure and the second Extension Phase visit (BL - EPH2)

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=40 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Total Body BMC Change at EPH2 From Baseline	-17.49 g Interval -275.0 to 93.65	—

SECONDARY outcome

Timeframe: Wk 48 (or last available measurement on study), Wk 72

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the first Extension Phase visit (Last- EPH1)

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=37 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Total Body BMC Change at EPH1 From Week 48 (or Last Visit on Study)	-27.80 g Interval -80.09 to 65.0	—

SECONDARY outcome

Timeframe: Wk 48 (or last available measurement on study), Wk 96

Population: Subjects who meet specific bone or renal criteria at Week 48 of the ATN 110 or ATN 113 study will be followed for an additional 48 weeks in the Extension Phase.

For subjects in the extension phase of the study, the last measured values at the ATN 110 or ATN 113 study week 48 visit will be compared with those measured at the Extension Phase visit 1 (EPH 1, 24 weeks after the ATN 110 or ATN 113 study week 48 visit) and EPH 2 (48 weeks after the ATN 110 or ATN 113 study week 48 visit). This measure shows the difference between the last measure on study and the second Extension Phase visit (Last- EPH2)

Outcome measures

Outcome measures
Measure	Subjects Enrolled in ATN 110 or ATN 113 n=40 Participants A subset of 101 participants who are enrolled in the ATN 110 or ATN 113 study will be recruited for participation in this study. There is no treatment or intervention for this study; however, all subjects will be on daily coformulated tenofovir/emtricitabine (TDF/FTC (Truvada®)) as part of the ATN 110 or ATN 113 study. FTC/TDF (Truvada®): There are no interventions for this study except that subjects will be administered FTC/TDF (Truvada®) will be administered as part of ATN 110 and ATN 113.	Low Exposure Group Lowest tertile of drug exposure, as measured by AUC (over the study duration) DBS RBC TFV-DP.
Changes in BMD/BMC in the Extension Phase: Total Body BMC Change at EPH2 From Week 48 (or Last Visit on Study)	-46.83 g Interval -145.0 to 41.84	—

Adverse Events

Subjects Enrolled in ATN 110 or ATN 113

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Bob Harris

Westat

Phone: 301-251-1500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Adolescent Medicine Trials Network (ATN) for HIV/AIDS Interventions Publication Policy outlines procedures for the development and review of abstracts, publications and presentations. The Adolescent Medicine Leadership Group (AMLG) retains custody of and primary rights to the data. Use of data must be approved by the protocol team and AMLG.
Publication restrictions are in place

Restriction type: OTHER