Trial Outcomes & Findings for Antiretroviral Therapy (ART) Persistence in Different Body Compartments in HIV Negative MSM (NCT NCT04039217)

Last Updated: 2022-02-22

Results Overview

Median drug levels of tenofovir (TFV), emtricitabine (FTC), and bictegravir (BIC) in plasma were determined. Concentrations below the limit of quantification (LOQ) are assigned a value of zero. The prespecified outcomes of interest are plasma concentrations of the components of Biktarvy at 24 and 120 hours after the initial dose. All other time points of sample collection are for future exploratory analyses and have not been analyzed. Only the time points of sample collection that were prespecified as primary study outcomes are presented here.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

20 participants

Primary outcome timeframe

Baseline (pre-dosing), 24 hours after the first dose, and 120 hours after first dose

Results posted on

2022-02-22

Participant Flow

Enrollment began on September 30, 2019 and all follow-up with participants was complete by August 28, 2020. Participants were enrolled at the Hope Clinic in Atlanta, Georgia, USA.

Enrollment began sequentially in Arm A, followed by Arms B and C. Arms A, B, and C were further broken down into two different sub-groups, determining the timing of the rectal biopsy procedure. Enrollment ended prior to enrolling Arm C.2. Participants were able to take part in multiple study arms, with at least 6 weeks after completion of one study arm before beginning another one. In total, 20 participants enrolled. Two individuals participated three times and one individual participated twice.

Participant milestones

Participant milestones
Measure	Biktarvy Participants were given 2 doses of the oral fixed dose combination anti-HIV medication Biktarvy (BIC/FTC/TAF) separated by 24 hours, and had specimens collected at different time points. * Arm A.1: blood collection occurred 2, 48, and 96 hours after the in-clinic dose of Biktarvy; rectal biopsy occurred 2 hours after the in-clinic dose of Biktarvy * Arm A.2: blood collection occurred 2, 48, and 96 hours after the in-clinic dose of Biktarvy; rectal biopsy occurred 48 hours after the in-clinic dose of Biktarvy * Arm A.3: blood collection occurred 2, 48, and 96 hours after the in-clinic dose of Biktarvy; rectal biopsy occurred 96 hours after the in-clinic dose of Biktarvy * Arm B.1: blood collection occurred 4, 26, and 120 hours after the in-clinic dose of Biktarvy; rectal biopsy occurred 4 hours after the in-clinic dose of Biktarvy * Arm B.2: blood collection occurred 4, 26, and 120 hours after the in-clinic dose of Biktarvy; rectal biopsy occurred 120 hours after the in-clinic dose of Biktarvy * Arm C.1: blood collection occurred 24, 28, and 72 hours after the in-clinic dose of Biktarvy; rectal biopsy occurred 24 hours after the in-clinic dose of Biktarvy * Arm C.2: blood collection occurred 24, 28, and 72 hours after the in-clinic dose of Biktarvy; rectal biopsy occurred 72 hours after the in-clinic dose of Biktarvy
Overall Study STARTED	20
Overall Study Started Study Arm A.1	4
Overall Study Completed Study Arm A.1	4
Overall Study Started Study Arm A.2	4
Overall Study Completed Study Arm A.2	4
Overall Study Started Study Arm A.3	4
Overall Study Completed Study Arm A.3	4
Overall Study Started Study Arm B.1	4
Overall Study Completed Study Arm B.1	4
Overall Study Started Study Arm B.2	4
Overall Study Completed Study Arm B.2	4
Overall Study Started Study Arm C.1	5
Overall Study Completed Study Arm C.1	4
Overall Study Started Study Arm C.2	0
Overall Study Completed Study Arm C.2	0
Overall Study COMPLETED	19
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Biktarvy Participants were given 2 doses of the oral fixed dose combination anti-HIV medication Biktarvy (BIC/FTC/TAF) separated by 24 hours, and had specimens collected at different time points. * Arm A.1: blood collection occurred 2, 48, and 96 hours after the in-clinic dose of Biktarvy; rectal biopsy occurred 2 hours after the in-clinic dose of Biktarvy * Arm A.2: blood collection occurred 2, 48, and 96 hours after the in-clinic dose of Biktarvy; rectal biopsy occurred 48 hours after the in-clinic dose of Biktarvy * Arm A.3: blood collection occurred 2, 48, and 96 hours after the in-clinic dose of Biktarvy; rectal biopsy occurred 96 hours after the in-clinic dose of Biktarvy * Arm B.1: blood collection occurred 4, 26, and 120 hours after the in-clinic dose of Biktarvy; rectal biopsy occurred 4 hours after the in-clinic dose of Biktarvy * Arm B.2: blood collection occurred 4, 26, and 120 hours after the in-clinic dose of Biktarvy; rectal biopsy occurred 120 hours after the in-clinic dose of Biktarvy * Arm C.1: blood collection occurred 24, 28, and 72 hours after the in-clinic dose of Biktarvy; rectal biopsy occurred 24 hours after the in-clinic dose of Biktarvy * Arm C.2: blood collection occurred 24, 28, and 72 hours after the in-clinic dose of Biktarvy; rectal biopsy occurred 72 hours after the in-clinic dose of Biktarvy
Overall Study Lost to Follow-up	1

Baseline Characteristics

Antiretroviral Therapy (ART) Persistence in Different Body Compartments in HIV Negative MSM

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Biktarvy n=20 Participants Participants were given two doses of the oral fixed dose combination anti-HIV medication Biktarvy (BIC/FTC/TAF) separated by 24 hours, and had specimens collected at different time points.
Age, Continuous	29.11 years STANDARD_DEVIATION 7.67 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	15 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (pre-dosing), 24 hours after the first dose, and 120 hours after first dose

Population: This analysis includes participants with usable samples at the indicated time points. Only the collection times of 24 and 120 hours post-dosing were prespecified for reporting.

Outcome measures

Outcome measures
Measure	Sample Collection 2, 48, and 96 Hours After First Dose of Biktarvy n=4 Participants Participants in study Arm A provided biological specimens 2, 48, and 96 hours after the in-clinic dose of Biktarvy. Participants had a rectal biopsy at one of the study visits.	Sample Collection 4, 26, and 120 Hours After First Dose of Biktarvy n=4 Participants Participants in study Arm B provided biological specimens 4, 26, and 120 hours after the in-clinic dose of Biktarvy. Participants also had a rectal biopsy at one of the study visits.	Sample Collection 24, 28, and 72 Hours After First Dose of Biktarvy n=4 Participants Participants in study Arm C will provide biological specimens 24, 28, and 72 hours after the in-clinic dose of Biktarvy. Participants also had a rectal biopsy at one of the study visits.
Median Drug Levels in Plasma TFV at Baseline (pre-dosing)	0 ng/mL Interval 0.0 to 0.0	0 ng/mL Interval 0.0 to 0.0	0 ng/mL Interval 0.0 to 0.0
Median Drug Levels in Plasma TFV at 24 hours after the first dose	—	—	0 ng/mL Interval 0.0 to 0.0
Median Drug Levels in Plasma TFV at 120 hours after first dose	—	0 ng/mL Interval 0.0 to 0.0	—
Median Drug Levels in Plasma FTC at Baseline (pre-dosing)	0 ng/mL Interval 0.0 to 0.0	0 ng/mL Interval 0.0 to 0.0	0 ng/mL Interval 0.0 to 0.0
Median Drug Levels in Plasma FTC at 24 hours after the first dose	—	—	33 ng/mL Interval 25.0 to 42.0
Median Drug Levels in Plasma FTC at 120 hours after first dose	—	0 ng/mL Interval 0.0 to 0.0	—
Median Drug Levels in Plasma BIC at Baseline (pre-dosing)	0 ng/mL Interval 0.0 to 0.0	0 ng/mL Interval 0.0 to 0.0	0 ng/mL Interval 0.0 to 0.0
Median Drug Levels in Plasma BIC at 24 hours after the first dose	—	—	1296 ng/mL Interval 623.0 to 1698.0
Median Drug Levels in Plasma BIC at 120 hours after first dose	—	267 ng/mL Interval 130.0 to 559.0	—

PRIMARY outcome

Timeframe: Baseline (pre-dosing), 24 hours after the first dose, and 120 hours after first dose

Population: This analysis includes participants with usable samples at the indicated time points. Only the collection times of 24 and 120 hours post-dosing were prespecified for reporting. Technical difficulties precluded the TFV-DP and FTC-TP measures in PBMCs for a large number of samples and therefore, data are not available for all drugs for all participants at these time points.

Median drug concentrations of tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) in PBMCs were determined. Concentrations below the limit of quantification (LOQ) are assigned a value of zero. The prespecified outcomes of interest are PBMC concentrations of the components of Biktarvy at 24 and 120 hours after the initial dose. All other time points of sample collection are for future exploratory analyses and have not been analyzed. Only the time points of sample collection that were prespecified as primary study outcomes are presented here.

Outcome measures

Outcome measures
Measure	Sample Collection 2, 48, and 96 Hours After First Dose of Biktarvy n=3 Participants Participants in study Arm A provided biological specimens 2, 48, and 96 hours after the in-clinic dose of Biktarvy. Participants had a rectal biopsy at one of the study visits.	Sample Collection 4, 26, and 120 Hours After First Dose of Biktarvy n=3 Participants Participants in study Arm B provided biological specimens 4, 26, and 120 hours after the in-clinic dose of Biktarvy. Participants also had a rectal biopsy at one of the study visits.	Sample Collection 24, 28, and 72 Hours After First Dose of Biktarvy n=3 Participants Participants in study Arm C will provide biological specimens 24, 28, and 72 hours after the in-clinic dose of Biktarvy. Participants also had a rectal biopsy at one of the study visits.
Median Drug Concentration in Peripheral Blood Mononuclear Cells (PBMCs) TFV-DP at Baseline (pre-dosing)	0 fmol/10^6 cells Interval 0.0 to 0.0	0 fmol/10^6 cells Interval 0.0 to 0.0	0 fmol/10^6 cells Interval 0.0 to 0.0
Median Drug Concentration in Peripheral Blood Mononuclear Cells (PBMCs) TFV-DP at 24 hours after the first dose	—	—	98 fmol/10^6 cells Interval 73.0 to 239.0
Median Drug Concentration in Peripheral Blood Mononuclear Cells (PBMCs) TFV-DP at 120 hours after first dose	—	189 fmol/10^6 cells Interval 136.0 to 273.0	—
Median Drug Concentration in Peripheral Blood Mononuclear Cells (PBMCs) FTC-TP at Baseline (pre-dosing)	0 fmol/10^6 cells Interval 0.0 to 0.0	0 fmol/10^6 cells Interval 0.0 to 0.0	0 fmol/10^6 cells Interval 0.0 to 0.0
Median Drug Concentration in Peripheral Blood Mononuclear Cells (PBMCs) FTC-TP at 24 hours after the first dose	—	—	3450 fmol/10^6 cells Interval 1723.0 to 4910.0
Median Drug Concentration in Peripheral Blood Mononuclear Cells (PBMCs) FTC-TP at 120 hours after first dose	—	1966 fmol/10^6 cells Interval 1268.0 to 2168.0	—

PRIMARY outcome

Timeframe: Baseline (pre-dosing), 24 hours after the first dose, and 120 hours after first dose

Population: This analysis includes participants with usable samples at the indicated time points. Only the collection times of 24 and 120 hours post-dosing were prespecified for reporting. Technical difficulties precluded the drug measures in rectal tissues for a large number of samples and therefore, data are not available for all drugs for all participants at these time points.

Median drug levels of TFV, FTC, and BIC in rectal tissue were determined. Concentrations below the limit of quantification (LOQ) are assigned a value of zero. The prespecified outcomes of interest are rectal tissue concentrations of the components of Biktarvy at 24 and 120 hours after the initial dose. All other time points of sample collection are for future exploratory analyses and have not been analyzed. Only the time points of sample collection that were prespecified as primary study outcomes are presented here.

Outcome measures

Outcome measures
Measure	Sample Collection 2, 48, and 96 Hours After First Dose of Biktarvy n=4 Participants Participants in study Arm A provided biological specimens 2, 48, and 96 hours after the in-clinic dose of Biktarvy. Participants had a rectal biopsy at one of the study visits.	Sample Collection 4, 26, and 120 Hours After First Dose of Biktarvy n=4 Participants Participants in study Arm B provided biological specimens 4, 26, and 120 hours after the in-clinic dose of Biktarvy. Participants also had a rectal biopsy at one of the study visits.	Sample Collection 24, 28, and 72 Hours After First Dose of Biktarvy n=4 Participants Participants in study Arm C will provide biological specimens 24, 28, and 72 hours after the in-clinic dose of Biktarvy. Participants also had a rectal biopsy at one of the study visits.
Median Drug Levels in Rectal Tissues TFV at Baseline (pre-dosing)	0 ng/mg Interval 0.0 to 0.0	0 ng/mg Interval 0.0 to 0.0	0 ng/mg Interval 0.0 to 0.0
Median Drug Levels in Rectal Tissues TFV at 24 hours after the first dose	—	—	0 ng/mg Interval 0.0 to 0.052
Median Drug Levels in Rectal Tissues TFV at 120 hours after first dose	—	0 ng/mg Interval 0.0 to 0.052	—
Median Drug Levels in Rectal Tissues FTC at Baseline (pre-dosing)	0 ng/mg Interval 0.0 to 0.0	0 ng/mg Interval 0.0 to 0.0	0 ng/mg Interval 0.0 to 0.0
Median Drug Levels in Rectal Tissues FTC at 24 hours after the first dose	—	—	0.233 ng/mg Interval 0.025 to 0.44
Median Drug Levels in Rectal Tissues FTC at 120 hours after first dose	—	0.064 ng/mg Interval 0.0 to 0.094	—
Median Drug Levels in Rectal Tissues BIC at Baseline (pre-dosing)	0 ng/mg Interval 0.0 to 0.0	0 ng/mg Interval 0.0 to 0.0	0 ng/mg Interval 0.0 to 0.0
Median Drug Levels in Rectal Tissues BIC at 24 hours after the first dose	—	—	0.105 ng/mg Interval 0.03 to 0.521
Median Drug Levels in Rectal Tissues BIC at 120 hours after first dose	—	0.020 ng/mg Interval 0.0 to 0.035	—

Adverse Events

Sample Collection 2, 48, and 96 Hours After First Dose of Biktarvy

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Sample Collection 4, 26, and 120 Hours After First Dose of Biktarvy

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Sample Collection 24, 28, and 72 Hours After First Dose of Biktarvy

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. Colleen Kelley

Emory University

Phone: 404-712-1823

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place