Trial Outcomes & Findings for Clinical Trial to Evaluate the Efficacy, Pharmacokinetics (PK) Interactions and Safety of Dolutegravir Plus 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in HIV-1-Infected Solid Organ Transplant Patients (NCT NCT03360682)

Results Overview

Change in pharmacokinetic parameters (Cmax, Cmin) of immunosuppressant Cyclosporine A (CsA)

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

19 participants

Primary outcome timeframe

24-hours before the switch and 24-hours 2 weeks after switching

Results posted on

2025-09-30

Participant Flow

HIV-1-infected adults (\>18) with kidney, liver, or heart transplant, on stable ART ≥6 months, HIV RNA \<50 c/mL for 12 months, no major resistance mutations, and HLA-B\*5701 negative. Some participants had switched to DTG + 2 NRTIs within the 48 weeks prior to study inclusion, while others switched at the time of enrollment. All participants were followed for 48 weeks from the start of DTG-based ART.

Participant milestones

Participant milestones
Measure	DTG + 2 NRTIs Dolutegravir plus 2 NRTIs in HIV-1-infected solid organ transplant recipients
Overall Study STARTED	19
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	DTG + 2 NRTIs Dolutegravir plus 2 NRTIs in HIV-1-infected solid organ transplant recipients
Overall Study Adverse Event	3

Baseline Characteristics

Clinical Trial to Evaluate the Efficacy, Pharmacokinetics (PK) Interactions and Safety of Dolutegravir Plus 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in HIV-1-Infected Solid Organ Transplant Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DTG + 2 NRTIs n=19 Participants Dolutegravir plus 2 NRTIs in HIV-1-infected solid organ transplant recipients
Age, Continuous	57 years n=99 Participants
Sex: Female, Male Female	8 Participants n=99 Participants
Sex: Female, Male Male	11 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants
Race (NIH/OMB) White	0 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	19 Participants n=99 Participants

PRIMARY outcome

Timeframe: 24-hours before the switch and 24-hours 2 weeks after switching

Change in pharmacokinetic parameters (Cmax, Cmin) of immunosuppressant Cyclosporine A (CsA)

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Subset Before ART Change n=2 Participants Sub-group analysis	Pharmacokinetic (PK) Subset After 2wk ART Change n=2 Participants Sub-group analysis
Change in Pharmacokinetic Parameters (Cmax, Cmin) of CsA Immunosuppressant Cmax	825 ng/mL Interval 686.0 to 946.0	299 ng/mL Interval 120.0 to 478.0
Change in Pharmacokinetic Parameters (Cmax, Cmin) of CsA Immunosuppressant Cmin	86.5 ng/mL Interval 83.0 to 90.0	98.5 ng/mL Interval 65.0 to 132.0

PRIMARY outcome

Timeframe: 24-hours before the switch and 24-hours 2 weeks after switching

Change in pharmacokinetic parameters (Cmax, Cmin) of immunosuppressant Mycophenolic Acid (MPA).

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Subset Before ART Change n=7 Participants Sub-group analysis	Pharmacokinetic (PK) Subset After 2wk ART Change n=7 Participants Sub-group analysis
Change in Pharmacokinetic Parameters (Cmax, Cmin) of MPA Immunosuppressant Cmax	6.3 μg/mL Interval 3.8 to 10.7	10.3 μg/mL Interval 5.3 to 12.9
Change in Pharmacokinetic Parameters (Cmax, Cmin) of MPA Immunosuppressant Cmin	1.9 μg/mL Interval 1.5 to 2.5	2.9 μg/mL Interval 1.7 to 4.0

PRIMARY outcome

Timeframe: 24-hours before the switch and 24-hours 2 weeks after switching

Outcome measures

Outcome measures
Measure	Pharmacokinetic (PK) Subset Before ART Change n=7 Participants Sub-group analysis	Pharmacokinetic (PK) Subset After 2wk ART Change n=7 Participants Sub-group analysis
Change in Pharmacokinetic Parameters (Cmax, Cmin) of Tacrolimus Immunosuppressant Cmax	14.4 ng/mL Interval 10.8 to 18.3	16.4 ng/mL Interval 12.1 to 18.7
Change in Pharmacokinetic Parameters (Cmax, Cmin) of Tacrolimus Immunosuppressant Cmin	6.2 ng/mL Interval 5.2 to 8.9	4.4 ng/mL Interval 4.3 to 8.5

Adverse Events

DTG + 2 NRTIs

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	DTG + 2 NRTIs n=19 participants at risk Dolutegravir plus 2 NRTIs in HIV-1-infected solid organ transplant recipients
Infections and infestations Cytomegalovirus infection	5.3% 1/19 • Number of events 1 • Up to 48 weeks of treatment plus 28 days after last dose in case of early withdrawal. Only adverse events leading to treatment discontinuation or considered clinically relevant are reported individually. All other AEs occurred with low frequency and were not considered related to treatment.

Other adverse events

Other adverse events
Measure	DTG + 2 NRTIs n=19 participants at risk Dolutegravir plus 2 NRTIs in HIV-1-infected solid organ transplant recipients
Nervous system disorders Insomnia	5.3% 1/19 • Number of events 1 • Up to 48 weeks of treatment plus 28 days after last dose in case of early withdrawal. Only adverse events leading to treatment discontinuation or considered clinically relevant are reported individually. All other AEs occurred with low frequency and were not considered related to treatment.
Nervous system disorders Tremor	5.3% 1/19 • Number of events 1 • Up to 48 weeks of treatment plus 28 days after last dose in case of early withdrawal. Only adverse events leading to treatment discontinuation or considered clinically relevant are reported individually. All other AEs occurred with low frequency and were not considered related to treatment.
Nervous system disorders Anxiety symptoms	5.3% 1/19 • Number of events 1 • Up to 48 weeks of treatment plus 28 days after last dose in case of early withdrawal. Only adverse events leading to treatment discontinuation or considered clinically relevant are reported individually. All other AEs occurred with low frequency and were not considered related to treatment.
General disorders Other	52.6% 10/19 • Number of events 10 • Up to 48 weeks of treatment plus 28 days after last dose in case of early withdrawal. Only adverse events leading to treatment discontinuation or considered clinically relevant are reported individually. All other AEs occurred with low frequency and were not considered related to treatment.
Endocrine disorders Hyperglycemia	5.3% 1/19 • Number of events 1 • Up to 48 weeks of treatment plus 28 days after last dose in case of early withdrawal. Only adverse events leading to treatment discontinuation or considered clinically relevant are reported individually. All other AEs occurred with low frequency and were not considered related to treatment.
Gastrointestinal disorders Diarrhea	15.8% 3/19 • Number of events 3 • Up to 48 weeks of treatment plus 28 days after last dose in case of early withdrawal. Only adverse events leading to treatment discontinuation or considered clinically relevant are reported individually. All other AEs occurred with low frequency and were not considered related to treatment.

Additional Information

Jose M. Miro Meda (PI), MD, PhD, Consultant, Infectious Diseases Service

Hospital Clínic/IDIBAPS, University of Barcelona

Phone: 93 227 54 30

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place