Trial Outcomes & Findings for A Study to Evaluate the Anti-inflammatory Effects of Letermovir (Prevymis) in Adults With Human Immunodeficiency Virus (HIV)-1 and Asymptomatic Cytomegalovirus (CMV) Who Are on Suppressive Antiretroviral Therapy, Plus Its Effect on Chronic Inflammation, HIV Persistence and Other Clinical Outcomes. (NCT NCT04840199)

Last Updated: 2025-03-04

Results Overview

The absolute change in sTNFRII from Baseline (average of study entry and treatment initiation visits) to Week 46/48 (average of Week 46 and Week 48), or the latest result in the treatment phase. Linear regression was used to estimate the mean change. The covariates were study arm and the gender and CD4 stratification factors.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

44 participants

Primary outcome timeframe

Measured at Baseline and Weeks 46 and 48

Results posted on

2025-03-04

Participant Flow

Participants enrolled from 15 US-based sites during the recruitment period of April 2022 to December 2022.

Participant milestones

Participant milestones
Measure	Letermovir Participants randomized to letermovir for 48 weeks followed by 12 weeks off letermovir Letermovir Oral Tablet: 480 mg administered orally once daily with or without food	No Anti-CMV Treatment Participants randomized to no study intervention for 60 weeks
Overall Study STARTED	21	23
Overall Study COMPLETED	10	11
Overall Study NOT COMPLETED	11	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Letermovir Participants randomized to letermovir for 48 weeks followed by 12 weeks off letermovir Letermovir Oral Tablet: 480 mg administered orally once daily with or without food	No Anti-CMV Treatment Participants randomized to no study intervention for 60 weeks
Overall Study Study Terminated by Sponsor	8	9
Overall Study Lost to Follow-up	0	2
Overall Study Withdrawal by Subject	2	0
Overall Study Found to Not Meet Eligibility Criteria After Randomization (Never Started Treatment)	1	1

Baseline Characteristics

Only quantifiable HIV-1 RNA records were log-transformed, where quantifiable HIV-1 RNA is defined as greater than or equal to the lower limit of quantification

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Letermovir n=19 Participants Participants randomized to letermovir for 48 weeks followed by 12 weeks off letermovir Letermovir Oral Tablet: 480 mg administered orally once daily with or without food	No Anti-CMV Treatment n=22 Participants Participants randomized to no study intervention for 60 weeks	Total n=41 Participants Total of all reporting groups
Age, Continuous	58 years n=19 Participants	58 years n=22 Participants	58 years n=41 Participants
Age, Customized 40-49 years	1 Participants n=19 Participants	5 Participants n=22 Participants	6 Participants n=41 Participants
Age, Customized 50-59 years	12 Participants n=19 Participants	9 Participants n=22 Participants	21 Participants n=41 Participants
Age, Customized 60-69 years	5 Participants n=19 Participants	8 Participants n=22 Participants	13 Participants n=41 Participants
Age, Customized 70 years and above	1 Participants n=19 Participants	0 Participants n=22 Participants	1 Participants n=41 Participants
Sex/Gender, Customized Sex at Birth and Use of Gender-Affirming Hormones · Female not taking testosterone (or do not know)	5 Participants n=19 Participants	7 Participants n=22 Participants	12 Participants n=41 Participants
Sex/Gender, Customized Sex at Birth and Use of Gender-Affirming Hormones · Male not taking feminizing hormones (or do not know)	14 Participants n=19 Participants	15 Participants n=22 Participants	29 Participants n=41 Participants
Sex: Female, Male Female	5 Participants n=19 Participants	7 Participants n=22 Participants	12 Participants n=41 Participants
Sex: Female, Male Male	14 Participants n=19 Participants	15 Participants n=22 Participants	29 Participants n=41 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=19 Participants	0 Participants n=22 Participants	0 Participants n=41 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=19 Participants	22 Participants n=22 Participants	41 Participants n=41 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=19 Participants	0 Participants n=22 Participants	0 Participants n=41 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=19 Participants	1 Participants n=22 Participants	2 Participants n=41 Participants
Race (NIH/OMB) Asian	0 Participants n=19 Participants	0 Participants n=22 Participants	0 Participants n=41 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=19 Participants	0 Participants n=22 Participants	0 Participants n=41 Participants
Race (NIH/OMB) Black or African American	8 Participants n=19 Participants	8 Participants n=22 Participants	16 Participants n=41 Participants
Race (NIH/OMB) White	9 Participants n=19 Participants	13 Participants n=22 Participants	22 Participants n=41 Participants
Race (NIH/OMB) More than one race	1 Participants n=19 Participants	0 Participants n=22 Participants	1 Participants n=41 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=19 Participants	0 Participants n=22 Participants	0 Participants n=41 Participants
Screening CD4+ T-cell Count <350 cells/mm^3	9 Participants n=19 Participants	9 Participants n=22 Participants	18 Participants n=41 Participants
Screening CD4+ T-cell Count ≥350 cells/mm^3	10 Participants n=19 Participants	13 Participants n=22 Participants	23 Participants n=41 Participants
Weight	90.9 kg n=19 Participants	87.9 kg n=22 Participants	90.3 kg n=41 Participants
Body Mass Index	27.1 kg/m^2 n=19 Participants	29.4 kg/m^2 n=22 Participants	29.4 kg/m^2 n=41 Participants
Body Mass Index Category Underweight (<18.5)	1 Participants n=19 Participants	0 Participants n=22 Participants	1 Participants n=41 Participants
Body Mass Index Category Normal (18.5-24.9)	4 Participants n=19 Participants	5 Participants n=22 Participants	9 Participants n=41 Participants
Body Mass Index Category Overweight (25-29.9)	5 Participants n=19 Participants	7 Participants n=22 Participants	12 Participants n=41 Participants
Body Mass Index Category Obese (≥30)	9 Participants n=19 Participants	10 Participants n=22 Participants	19 Participants n=41 Participants
Antiretroviral Therapy Regimen BIC/FTC/TAF	4 Participants n=19 Participants	7 Participants n=22 Participants	11 Participants n=41 Participants
Antiretroviral Therapy Regimen DOR/DTG/FTC/TDF	0 Participants n=19 Participants	1 Participants n=22 Participants	1 Participants n=41 Participants
Antiretroviral Therapy Regimen DTG/3TC	1 Participants n=19 Participants	2 Participants n=22 Participants	3 Participants n=41 Participants
Antiretroviral Therapy Regimen DTG/ABC/3TC	3 Participants n=19 Participants	2 Participants n=22 Participants	5 Participants n=41 Participants
Antiretroviral Therapy Regimen DTG/FTC/TAF	4 Participants n=19 Participants	2 Participants n=22 Participants	6 Participants n=41 Participants
Antiretroviral Therapy Regimen EVG/COBI/FTC/TAF	4 Participants n=19 Participants	2 Participants n=22 Participants	6 Participants n=41 Participants
Antiretroviral Therapy Regimen RPV/CAB	1 Participants n=19 Participants	2 Participants n=22 Participants	3 Participants n=41 Participants
Antiretroviral Therapy Regimen RPV/DRV/COBI/FTC/TAF	1 Participants n=19 Participants	0 Participants n=22 Participants	1 Participants n=41 Participants
Antiretroviral Therapy Regimen RPV/DTG	1 Participants n=19 Participants	2 Participants n=22 Participants	3 Participants n=41 Participants
Antiretroviral Therapy Regimen RPV/DTG/FTC/TAF	0 Participants n=19 Participants	1 Participants n=22 Participants	1 Participants n=41 Participants
Antiretroviral Therapy Regimen RPV/FTC/TAF	0 Participants n=19 Participants	1 Participants n=22 Participants	1 Participants n=41 Participants
CD4 Count	380 cells/mm^3 n=19 Participants	461 cells/mm^3 n=22 Participants	384 cells/mm^3 n=41 Participants
HIV-1 RNA <20 copies/mL	11 Participants n=19 Participants	13 Participants n=22 Participants	24 Participants n=41 Participants
HIV-1 RNA <40 copies/mL	5 Participants n=19 Participants	6 Participants n=22 Participants	11 Participants n=41 Participants
HIV-1 RNA <128 copies/mL	1 Participants n=19 Participants	0 Participants n=22 Participants	1 Participants n=41 Participants
HIV-1 RNA ≥Lower Limit of Quantification	2 Participants n=19 Participants	3 Participants n=22 Participants	5 Participants n=41 Participants
HIV-1 RNA	1.49 log10 copies/mL n=2 Participants • Only quantifiable HIV-1 RNA records were log-transformed, where quantifiable HIV-1 RNA is defined as greater than or equal to the lower limit of quantification	1.49 log10 copies/mL n=3 Participants • Only quantifiable HIV-1 RNA records were log-transformed, where quantifiable HIV-1 RNA is defined as greater than or equal to the lower limit of quantification	1.49 log10 copies/mL n=5 Participants • Only quantifiable HIV-1 RNA records were log-transformed, where quantifiable HIV-1 RNA is defined as greater than or equal to the lower limit of quantification
Hemoglobin	14.2 g/dL n=19 Participants	14.2 g/dL n=22 Participants	14.2 g/dL n=41 Participants
Platelet Count	215000 platelets/mm^3 n=19 Participants	231500 platelets/mm^3 n=22 Participants	215000 platelets/mm^3 n=41 Participants
Creatinine Clearance	87.4 mL/min n=19 Participants	86.8 mL/min n=22 Participants	87.4 mL/min n=41 Participants
eGFR	80.0 mL/min/1.73 m^2 n=14 Participants • eGFR reporting was optional	75.0 mL/min/1.73 m^2 n=14 Participants • eGFR reporting was optional	77.5 mL/min/1.73 m^2 n=28 Participants • eGFR reporting was optional
Soluble TNF Receptor Type II (sTNFRII)	3.39 log10 pg/mL STANDARD_DEVIATION 0.12 • n=17 Participants • Baseline sTNFRII was only calculated for participants in the per-protocol population, where baseline refers to the average of study entry and treatment initiation measures	3.40 log10 pg/mL STANDARD_DEVIATION 0.10 • n=22 Participants • Baseline sTNFRII was only calculated for participants in the per-protocol population, where baseline refers to the average of study entry and treatment initiation measures	3.39 log10 pg/mL STANDARD_DEVIATION 0.11 • n=39 Participants • Baseline sTNFRII was only calculated for participants in the per-protocol population, where baseline refers to the average of study entry and treatment initiation measures
Soluble TNF Receptor Type II	3.37 log10 pg/mL n=17 Participants • Baseline sTNFRII was only calculated for participants in the per-protocol population, where baseline refers to the average of study entry and treatment initiation measures	3.39 log10 pg/mL n=22 Participants • Baseline sTNFRII was only calculated for participants in the per-protocol population, where baseline refers to the average of study entry and treatment initiation measures	3.39 log10 pg/mL n=39 Participants • Baseline sTNFRII was only calculated for participants in the per-protocol population, where baseline refers to the average of study entry and treatment initiation measures

PRIMARY outcome

Timeframe: Measured at Baseline and Weeks 46 and 48

Population: Per-protocol population: All mITT participants who did not prematurely discontinue study product prior to Week 8, had self-reported adherence \>50% (letermovir arm only) and did not have a confirmed HIV-1 virologic failure during the treatment phase.

Outcome measures

Outcome measures
Measure	Letermovir n=17 Participants Participants randomized to letermovir for 48 weeks followed by 12 weeks off letermovir Letermovir Oral Tablet: 480 mg administered orally once daily with or without food	No Anti-CMV Treatment n=22 Participants Participants randomized to no study intervention for 60 weeks
Change (Absolute) in sTNFRII	-0.028 log10 pg/mL Interval -0.064 to 0.008	0.003 log10 pg/mL Interval -0.029 to 0.036

SECONDARY outcome

Timeframe: Measured from study entry through Week 48

Population: Modified intent to treat population: all eligible, randomized participants excluding letermovir arm participants who did not initiate study treatment.

Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Adverse events were graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. Confirmed virologic failure was defined as two consecutive HIV-1 RNA levels ≥200 copies/mL by real-time HIV-1 RNA testing. Participants with a plasma HIV-1 RNA ≥200 copies/mL at any visit had a confirmatory viral load obtained as soon as possible but within 14 days after the first sample was drawn, if possible. If the consecutive measurement of HIV-1 RNA was also ≥200 copies/mL, the participant was considered to have confirmed virologic failure.

Outcome measures

Outcome measures
Measure	Letermovir n=19 Participants Participants randomized to letermovir for 48 weeks followed by 12 weeks off letermovir Letermovir Oral Tablet: 480 mg administered orally once daily with or without food	No Anti-CMV Treatment n=22 Participants Participants randomized to no study intervention for 60 weeks
Occurrence of Grade ≥3 AEs or Confirmed HIV-1 Virologic Failure	5 Participants	2 Participants

SECONDARY outcome

Timeframe: Measured at Baseline and Weeks 8, 46, 48, 52 and 60

When the number of detection outcomes was sufficient, binary repeated oral CMV DNA detection (yes/no) was modeled with generalized estimating equations (GEE) to estimate the weekly rate of change (slope). The covariates were study arm and the gender and CD4 stratification factors, as well as a three-level period effect (early treatment phase \[through Week 8\], late treatment phase, post-treatment phase) and its interaction with the study arm. Due to the small sample size and small number of detectable CMV DNA results, the GEE model was not able to provide estimates. Cross-sectional CMV DNA detection summaries have been provided instead.

Outcome measures

Outcome measures
Measure	Letermovir n=17 Participants Participants randomized to letermovir for 48 weeks followed by 12 weeks off letermovir Letermovir Oral Tablet: 480 mg administered orally once daily with or without food	No Anti-CMV Treatment n=22 Participants Participants randomized to no study intervention for 60 weeks
Rate of Change in Odds of Oral CMV DNA Detection Baseline · Detected	2 Participants	1 Participants
Rate of Change in Odds of Oral CMV DNA Detection Baseline · Not detected	15 Participants	20 Participants
Rate of Change in Odds of Oral CMV DNA Detection Baseline · No result	0 Participants	1 Participants
Rate of Change in Odds of Oral CMV DNA Detection Week 8 · Detected	0 Participants	1 Participants
Rate of Change in Odds of Oral CMV DNA Detection Week 8 · Not detected	15 Participants	19 Participants
Rate of Change in Odds of Oral CMV DNA Detection Week 8 · No result	2 Participants	2 Participants
Rate of Change in Odds of Oral CMV DNA Detection Week 46 · Detected	0 Participants	1 Participants
Rate of Change in Odds of Oral CMV DNA Detection Week 46 · Not detected	12 Participants	15 Participants
Rate of Change in Odds of Oral CMV DNA Detection Week 46 · No result	5 Participants	6 Participants
Rate of Change in Odds of Oral CMV DNA Detection Week 48 · Detected	0 Participants	1 Participants
Rate of Change in Odds of Oral CMV DNA Detection Week 48 · Not detected	13 Participants	17 Participants
Rate of Change in Odds of Oral CMV DNA Detection Week 48 · No result	4 Participants	4 Participants
Rate of Change in Odds of Oral CMV DNA Detection Week 52 · Detected	0 Participants	1 Participants
Rate of Change in Odds of Oral CMV DNA Detection Week 52 · Not detected	12 Participants	11 Participants
Rate of Change in Odds of Oral CMV DNA Detection Week 52 · No result	5 Participants	10 Participants
Rate of Change in Odds of Oral CMV DNA Detection Week 60 · Detected	0 Participants	2 Participants
Rate of Change in Odds of Oral CMV DNA Detection Week 60 · Not detected	8 Participants	6 Participants
Rate of Change in Odds of Oral CMV DNA Detection Week 60 · No result	9 Participants	14 Participants

SECONDARY outcome

Timeframe: Measured at Baseline and Weeks 8, 46, 48, 52 and 60

When the number of detection outcomes was sufficient, binary repeated genital CMV DNA detection (yes/no) was modeled with generalized estimating equations (GEE) to estimate the weekly rate of change (slope). The covariates were study arm and the gender and CD4 stratification factors, as well as a three-level period effect (early treatment phase \[through Week 8\], late treatment phase, post-treatment phase) and its interaction with the study arm. The model estimates do not reflect the odds of detection, but rather, the change in the odds of detection per week on the multiplicative scale.

Outcome measures

Outcome measures
Measure	Letermovir n=17 Participants Participants randomized to letermovir for 48 weeks followed by 12 weeks off letermovir Letermovir Oral Tablet: 480 mg administered orally once daily with or without food	No Anti-CMV Treatment n=22 Participants Participants randomized to no study intervention for 60 weeks
Rate of Change in Odds of Genital CMV DNA Detection Early treatment phase	0.94 change in odds of detection per week Interval 0.86 to 1.03	1.04 change in odds of detection per week Interval 0.96 to 1.13
Rate of Change in Odds of Genital CMV DNA Detection Late treatment phase	0.95 change in odds of detection per week Interval 0.91 to 0.99	1.03 change in odds of detection per week Interval 0.99 to 1.07
Rate of Change in Odds of Genital CMV DNA Detection Post treatment phase	1.05 change in odds of detection per week Interval 1.01 to 1.09	0.89 change in odds of detection per week Interval 0.68 to 1.18

SECONDARY outcome

Timeframe: Measured at Baseline and Weeks 8, 48 and 60

When the number of detection outcomes was sufficient, binary repeated rectal CMV DNA detection (yes/no) was modeled with generalized estimating equations (GEE) to estimate the weekly rate of change (slope). The covariates were study arm and the gender and CD4 stratification factors, as well as a three-level period effect (early treatment phase \[through Week 8\], late treatment phase, post-treatment phase) and its interaction with the study arm. Due to the small sample size and small number of detectable CMV DNA results, the GEE model was not able to provide estimates. Cross-sectional CMV DNA detection summaries have been provided instead.

Outcome measures

Outcome measures
Measure	Letermovir n=17 Participants Participants randomized to letermovir for 48 weeks followed by 12 weeks off letermovir Letermovir Oral Tablet: 480 mg administered orally once daily with or without food	No Anti-CMV Treatment n=22 Participants Participants randomized to no study intervention for 60 weeks
Rate of Change in Odds of Rectal CMV DNA Detection Baseline · Detected	1 Participants	1 Participants
Rate of Change in Odds of Rectal CMV DNA Detection Baseline · Not detected	16 Participants	21 Participants
Rate of Change in Odds of Rectal CMV DNA Detection Baseline · No result	0 Participants	0 Participants
Rate of Change in Odds of Rectal CMV DNA Detection Week 8 · Detected	0 Participants	0 Participants
Rate of Change in Odds of Rectal CMV DNA Detection Week 8 · Not detected	15 Participants	20 Participants
Rate of Change in Odds of Rectal CMV DNA Detection Week 8 · No result	2 Participants	2 Participants
Rate of Change in Odds of Rectal CMV DNA Detection Week 48 · Detected	0 Participants	2 Participants
Rate of Change in Odds of Rectal CMV DNA Detection Week 48 · Not detected	14 Participants	15 Participants
Rate of Change in Odds of Rectal CMV DNA Detection Week 48 · No result	3 Participants	5 Participants
Rate of Change in Odds of Rectal CMV DNA Detection Week 60 · Detected	0 Participants	0 Participants
Rate of Change in Odds of Rectal CMV DNA Detection Week 60 · Not detected	7 Participants	8 Participants
Rate of Change in Odds of Rectal CMV DNA Detection Week 60 · No result	10 Participants	14 Participants

SECONDARY outcome

Timeframe: Measured at Baseline and Weeks 8, 46, 48, 52 and 60

When the number of detection outcomes was sufficient, binary repeated plasma CMV DNA detection (yes/no) was modeled with generalized estimating equations (GEE) to estimate the weekly rate of change (slope). The covariates were study arm and the gender and CD4 stratification factors, as well as a three-level period effect (early treatment phase \[through Week 8\], late treatment phase, post-treatment phase) and its interaction with the study arm. Due to the small sample size and small number of detectable CMV DNA results, the GEE model was not able to provide estimates. Cross-sectional CMV DNA detection summaries have been provided instead.

Outcome measures

Outcome measures
Measure	Letermovir n=17 Participants Participants randomized to letermovir for 48 weeks followed by 12 weeks off letermovir Letermovir Oral Tablet: 480 mg administered orally once daily with or without food	No Anti-CMV Treatment n=22 Participants Participants randomized to no study intervention for 60 weeks
Rate of Change in Odds of Plasma CMV DNA Detection Week 48 · No detected	13 Participants	18 Participants
Rate of Change in Odds of Plasma CMV DNA Detection Week 48 · No result	4 Participants	4 Participants
Rate of Change in Odds of Plasma CMV DNA Detection Week 52 · Detected	0 Participants	0 Participants
Rate of Change in Odds of Plasma CMV DNA Detection Week 52 · No detected	11 Participants	11 Participants
Rate of Change in Odds of Plasma CMV DNA Detection Baseline · Detected	0 Participants	0 Participants
Rate of Change in Odds of Plasma CMV DNA Detection Baseline · No detected	17 Participants	20 Participants
Rate of Change in Odds of Plasma CMV DNA Detection Baseline · No result	0 Participants	2 Participants
Rate of Change in Odds of Plasma CMV DNA Detection Week 8 · Detected	0 Participants	0 Participants
Rate of Change in Odds of Plasma CMV DNA Detection Week 8 · No detected	16 Participants	20 Participants
Rate of Change in Odds of Plasma CMV DNA Detection Week 8 · No result	1 Participants	2 Participants
Rate of Change in Odds of Plasma CMV DNA Detection Week 46 · Detected	0 Participants	0 Participants
Rate of Change in Odds of Plasma CMV DNA Detection Week 46 · No detected	13 Participants	16 Participants
Rate of Change in Odds of Plasma CMV DNA Detection Week 46 · No result	4 Participants	6 Participants
Rate of Change in Odds of Plasma CMV DNA Detection Week 48 · Detected	0 Participants	0 Participants
Rate of Change in Odds of Plasma CMV DNA Detection Week 52 · No result	6 Participants	11 Participants
Rate of Change in Odds of Plasma CMV DNA Detection Week 60 · Detected	0 Participants	0 Participants
Rate of Change in Odds of Plasma CMV DNA Detection Week 60 · No detected	7 Participants	8 Participants
Rate of Change in Odds of Plasma CMV DNA Detection Week 60 · No result	10 Participants	14 Participants

SECONDARY outcome

Timeframe: Measured at Baseline and Weeks 8, 24, 46, 48, 52 and 60

Repeated, continuous sCD163 was modeled with generalized estimating equations (GEE) to estimate the weekly rate of change (slope). The covariates were study arm and the gender and CD4 stratification factors, as well as a three-level period effect (early treatment phase \[through Week 8\], late treatment phase, post-treatment phase) and its interaction with the study arm.

Outcome measures

Outcome measures
Measure	Letermovir n=17 Participants Participants randomized to letermovir for 48 weeks followed by 12 weeks off letermovir Letermovir Oral Tablet: 480 mg administered orally once daily with or without food	No Anti-CMV Treatment n=22 Participants Participants randomized to no study intervention for 60 weeks
Rate of Change in sCD163 Early treatment phase	0.0012 log10 ng/mL/week Interval -0.0031 to 0.0055	0.0010 log10 ng/mL/week Interval -0.0038 to 0.0057
Rate of Change in sCD163 Late treatment phase	-0.0005 log10 ng/mL/week Interval -0.0012 to 0.0003	0.0002 log10 ng/mL/week Interval -0.0007 to 0.0012
Rate of Change in sCD163 Post treatment phase	0.0028 log10 ng/mL/week Interval -0.0001 to 0.0057	-0.0028 log10 ng/mL/week Interval -0.0083 to 0.0027

SECONDARY outcome

Timeframe: Measured at Baseline and Weeks 8, 24, 46, 48, 52 and 60

Repeated, continuous sTNFRII was modeled with generalized estimating equations (GEE) to estimate the weekly rate of change (slope). The covariates were study arm and the gender and CD4 stratification factors, as well as a three-level period effect (early treatment phase \[through Week 8\], late treatment phase, post-treatment phase) and its interaction with the study arm.

Outcome measures

Outcome measures
Measure	Letermovir n=17 Participants Participants randomized to letermovir for 48 weeks followed by 12 weeks off letermovir Letermovir Oral Tablet: 480 mg administered orally once daily with or without food	No Anti-CMV Treatment n=22 Participants Participants randomized to no study intervention for 60 weeks
Rate of Change in sTNFRII Early treatment phase	0.0009 log10 pg/mL/week Interval -0.0032 to 0.005	0.0000 log10 pg/mL/week Interval -0.0027 to 0.0026
Rate of Change in sTNFRII Late treatment phase	-0.0010 log10 pg/mL/week Interval -0.0019 to -0.0001	-0.0001 log10 pg/mL/week Interval -0.0009 to 0.0007
Rate of Change in sTNFRII Post treatment phase	0.0001 log10 pg/mL/week Interval -0.0015 to 0.0018	-0.0021 log10 pg/mL/week Interval -0.005 to 0.0007

Adverse Events

Letermovir

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

No Anti-CMV Treatment

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Letermovir n=19 participants at risk Participants randomized to letermovir for 48 weeks followed by 12 weeks off letermovir Letermovir Oral Tablet: 480 mg administered orally once daily with or without food	No Anti-CMV Treatment n=22 participants at risk Participants randomized to no study intervention for 60 weeks
Infections and infestations Influenza	5.3% 1/19 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)	0.00% 0/22 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)
Infections and infestations Pneumonia	5.3% 1/19 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)	0.00% 0/22 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)
Injury, poisoning and procedural complications Failed back surgery syndrome	0.00% 0/19 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)	4.5% 1/22 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)

Other adverse events

Other adverse events
Measure	Letermovir n=19 participants at risk Participants randomized to letermovir for 48 weeks followed by 12 weeks off letermovir Letermovir Oral Tablet: 480 mg administered orally once daily with or without food	No Anti-CMV Treatment n=22 participants at risk Participants randomized to no study intervention for 60 weeks
Gastrointestinal disorders Diarrhoea	15.8% 3/19 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)	0.00% 0/22 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)
General disorders Fatigue	5.3% 1/19 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)	0.00% 0/22 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)
Infections and infestations COVID-19	15.8% 3/19 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)	18.2% 4/22 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)
Injury, poisoning and procedural complications Soft tissue injury	5.3% 1/19 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)	0.00% 0/22 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)
Investigations CD4 lymphocytes decreased	5.3% 1/19 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)	4.5% 1/22 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)
Investigations Creatinine renal clearance decreased	5.3% 1/19 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)	0.00% 0/22 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)
Investigations Low density lipoprotein increased	5.3% 1/19 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)	0.00% 0/22 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)
Investigations Lymphocyte count decreased	5.3% 1/19 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)	0.00% 0/22 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)
Nervous system disorders Headache	10.5% 2/19 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)	0.00% 0/22 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)
Reproductive system and breast disorders Priapism	0.00% 0/19 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)	4.5% 1/22 • From study entry to Week 60, or premature study discontinuation The DAIDS AE Grading Table (Version 2.0) was used for grading adverse events: * Grade ≥3 AEs * All AEs that led to a change in study treatment/intervention regardless of grade * All AEs meeting SAE definition or EAE reporting requirement * All Grade ≥2 cardiac arrhythmias (i.e., atrial fibrillation, atrial flutter, etc.) * Any Grade ≥1 SARS-CoV-2 or monkeypox infection or AE related to these infections (including any related signs or symptoms Grade ≥1) * Any acute febrile illness (\>101°F)

Additional Information

ACTG Clinicaltrials.gov Coordinator

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Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place