Trial Outcomes & Findings for Dolutegravir in Reservoirs (NCT NCT02924389)

Last Updated: 2022-12-29

Results Overview

Dolutegravir concentrations in blood plasma are assessed as the maximum dolutegravir concentration (Cmax) and 24 hour trough (lowest) concentration (C24h) of dolutegravir in micrograms per milliliter (µg/mL). Blood samples for pharmacokinetics were obtained prior to dosing (hour 0) and 1, 2, 3, 4, 6, 8, and 24 hours after dosing.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

22 participants

Primary outcome timeframe

Day 84 (hour 0 through 24)

Results posted on

2022-12-29

Participant Flow

Participant enrollment began September 2016 and all follow up was complete by September 11, 2019. Participants were enrolled at the Grady Ponce de Leon Center and Grady Health System in Atlanta, Georgia, USA.

Participant milestones

Participant milestones
Measure	Anti-retroviral (ARV) Naïve Males Males diagnosed with HIV undergoing serial blood and tissue rectal sampling for twelve weeks after initiating anti-retroviral (ARV) therapy as prescribed by their physician. Participants were treated with either Triumeq (abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg), or Truvada (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) plus and dolutegravir (50 mg), or Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg) plus dolutegravir (50 mg).	Anti-retroviral (ARV) Naïve Females Females diagnosed with HIV undergoing serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Participants were treated with either Triumeq (abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg), or Truvada (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) plus and dolutegravir (50 mg), or Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg) plus dolutegravir (50 mg).
Overall Study STARTED	16	6
Overall Study COMPLETED	8	6
Overall Study NOT COMPLETED	8	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Anti-retroviral (ARV) Naïve Males Males diagnosed with HIV undergoing serial blood and tissue rectal sampling for twelve weeks after initiating anti-retroviral (ARV) therapy as prescribed by their physician. Participants were treated with either Triumeq (abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg), or Truvada (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) plus and dolutegravir (50 mg), or Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg) plus dolutegravir (50 mg).	Anti-retroviral (ARV) Naïve Females Females diagnosed with HIV undergoing serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Participants were treated with either Triumeq (abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg), or Truvada (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) plus and dolutegravir (50 mg), or Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg) plus dolutegravir (50 mg).
Overall Study Lost to Follow-up	1	0
Overall Study Physician Decision	2	0
Overall Study Withdrawal by Subject	3	0
Overall Study Participant began ARVs prior to study intervention	2	0

Baseline Characteristics

Dolutegravir in Reservoirs

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Anti-retroviral (ARV) Naïve Males n=16 Participants Males diagnosed with HIV undergoing serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Participants were treated with either Triumeq (abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg), or Truvada (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) plus and dolutegravir (50 mg), or Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg) plus dolutegravir (50 mg).	Anti-retroviral (ARV) Naïve Females n=6 Participants Females diagnosed with HIV undergoing serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Participants were treated with either Triumeq (abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg), or Truvada (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) plus and dolutegravir (50 mg), or Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg) plus dolutegravir (50 mg).	Total n=22 Participants Total of all reporting groups
Age, Continuous	35.2 years STANDARD_DEVIATION 9.8 • n=5 Participants	45.6 years STANDARD_DEVIATION 8.0 • n=7 Participants	38.0 years STANDARD_DEVIATION 10.3 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	0 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=5 Participants	6 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	14 Participants n=5 Participants	5 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	16 Participants n=5 Participants	6 Participants n=7 Participants	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 84 (hour 0 through 24)

Population: This analysis includes participants who completed at least one study visit. Fourteen participants completed all study visits and 2 completed a portion of study visits. Males and females are combined for all primary and secondary analyses and are separated only for exploratory study outcomes.

Outcome measures

Outcome measures
Measure	Anti-retroviral (ARV) Naïve Males and Females n=16 Participants Males and females diagnosed with HIV undergoing serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Participants were treated with either Triumeq (abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg), or Truvada (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) plus and dolutegravir (50 mg), or Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg) plus dolutegravir (50 mg).	HIV RNA Non-suppressors Males and females diagnosed with HIV undergoing serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Non-suppressors are participants with baseline detectable rectal tissue HIV RNA who did not achieve rectal tissue HIV RNA suppression during the 12 week study.
Dolutegravir Concentration First-dose pharmacokinetics (Cmax)	2.01 µg/mL Interval 1.17 to 2.32	—
Dolutegravir Concentration Steady state pharmacokinetics (Cmax)	2.34 µg/mL Interval 1.84 to 3.04	—
Dolutegravir Concentration Trough dolutegravir concentration (C24h)	0.56 µg/mL Interval 0.44 to 1.21	—

PRIMARY outcome

Timeframe: Day 84 (hour 0 through 24)

Time of maximum dolutegravir concentration is assessed in hours for the time periods of after the first dose and during steady state. Blood samples for pharmacokinetics were obtained prior to dosing (hour 0) and 1, 2, 3, 4, 6, 8, and 24 hours after dosing.

Outcome measures

Outcome measures
Measure	Anti-retroviral (ARV) Naïve Males and Females n=16 Participants Males and females diagnosed with HIV undergoing serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Participants were treated with either Triumeq (abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg), or Truvada (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) plus and dolutegravir (50 mg), or Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg) plus dolutegravir (50 mg).	HIV RNA Non-suppressors Males and females diagnosed with HIV undergoing serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Non-suppressors are participants with baseline detectable rectal tissue HIV RNA who did not achieve rectal tissue HIV RNA suppression during the 12 week study.
Time of Maximum Dolutegravir Concentration Steady state pharmacokinetics (Tmax)	3.0 hours Interval 3.0 to 4.0	—
Time of Maximum Dolutegravir Concentration First-dose pharmacokinetics (Tmax)	1.5 hours Interval 1.0 to 3.8	—

PRIMARY outcome

Timeframe: Day 84 (hour 0 through 24)

The area under the dolutegravir plasma concentration vs time curve in a 24 hour period (AUC24h) is assessed in hours times micrograms per millimeters (h\* µg/mL) for the time periods of after the first dose and during steady state. Blood samples for pharmacokinetics were obtained prior to dosing (hour 0) and 1, 2, 3, 4, 6, 8, and 24 hours after dosing.

Outcome measures

Outcome measures
Measure	Anti-retroviral (ARV) Naïve Males and Females n=16 Participants Males and females diagnosed with HIV undergoing serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Participants were treated with either Triumeq (abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg), or Truvada (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) plus and dolutegravir (50 mg), or Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg) plus dolutegravir (50 mg).	HIV RNA Non-suppressors Males and females diagnosed with HIV undergoing serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Non-suppressors are participants with baseline detectable rectal tissue HIV RNA who did not achieve rectal tissue HIV RNA suppression during the 12 week study.
Area Under the Dolutegravir Plasma Concentration vs Time Curve First-dose pharmacokinetics (AUC24h)	22.30 h* µg/mL Interval 15.03 to 30.85	—
Area Under the Dolutegravir Plasma Concentration vs Time Curve Steady state pharmacokinetics (AUC24h)	27.24 h* µg/mL Interval 24.48 to 48.08	—

SECONDARY outcome

Timeframe: Up to Day 84

Population: Due to lack of viral dynamic decline in PBMCs and inability to measure intracellular dolutegravir consistently with the assays, this secondary outcome could not be assessed.

Dolutegravir concentrations in peripheral blood mononuclear cells required for HIV viral load decline.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 2, Week 6, Week 12

Population: This analysis includes the first 12 study participants; the analysis was not extended to subsequent participants due to study findings being sufficient from the first 12 participants. One participant was removed from this analysis because they had undetectable virus in rectal tissue at the baseline assessment.

Rectal dolutegravir concentrations in rectal tissue stratified by virologic suppressors vs non-suppressors.

Outcome measures

Outcome measures
Measure	Anti-retroviral (ARV) Naïve Males and Females n=3 Participants Males and females diagnosed with HIV undergoing serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Participants were treated with either Triumeq (abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg), or Truvada (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) plus and dolutegravir (50 mg), or Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg) plus dolutegravir (50 mg).	HIV RNA Non-suppressors n=8 Participants Males and females diagnosed with HIV undergoing serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Non-suppressors are participants with baseline detectable rectal tissue HIV RNA who did not achieve rectal tissue HIV RNA suppression during the 12 week study.
Dolutegravir Concentration in Rectal Tissue Week 2	1606 ng/mL Interval 1420.0 to 1791.0	749 ng/mL Interval 608.0 to 1559.0
Dolutegravir Concentration in Rectal Tissue Week 6	724 ng/mL Interval 102.0 to 1579.0	625 ng/mL Interval 134.0 to 1452.0
Dolutegravir Concentration in Rectal Tissue Week 12	473 ng/mL Interval 163.0 to 12369.0	373 ng/mL Interval 2.65 to 621.0

Adverse Events

Anti-retroviral (ARV) Naïve Males

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Anti-retroviral (ARV) Naïve Females

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Cecile Lahiri, MD

Emory University

Phone: 404-616-6306

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Anti-retroviral (ARV) Naïve Males n=16 participants at risk Males diagnosed with HIV undergoing serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Participants were treated with either Triumeq (abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg), or Truvada (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) plus and dolutegravir (50 mg), or Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg) plus dolutegravir (50 mg).	Anti-retroviral (ARV) Naïve Females n=6 participants at risk Females diagnosed with HIV undergoing serial blood and tissue rectal sampling for twelve weeks after initiating ARV therapy as prescribed by their physician. Participants were treated with either Triumeq (abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg), or Truvada (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) plus and dolutegravir (50 mg), or Descovy (emtricitabine 200 mg/tenofovir alafenamide 25 mg) plus dolutegravir (50 mg).
Gastrointestinal disorders Diarrhea	12.5% 2/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	0.00% 0/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
Surgical and medical procedures Rectal bleeding	31.2% 5/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	50.0% 3/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
Surgical and medical procedures Rectal/anal pain	12.5% 2/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	16.7% 1/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
Respiratory, thoracic and mediastinal disorders Nasal congestion	12.5% 2/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	33.3% 2/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
Respiratory, thoracic and mediastinal disorders Cough	18.8% 3/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	33.3% 2/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
Skin and subcutaneous tissue disorders Rash	31.2% 5/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	0.00% 0/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
General disorders Fatigue	0.00% 0/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	33.3% 2/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
General disorders Nausea	18.8% 3/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	33.3% 2/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
Gastrointestinal disorders Vomiting	6.2% 1/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	16.7% 1/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
General disorders Night sweats	6.2% 1/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	16.7% 1/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
Respiratory, thoracic and mediastinal disorders Pharyngitis	6.2% 1/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	33.3% 2/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
Psychiatric disorders Anxiety	12.5% 2/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	16.7% 1/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
Psychiatric disorders Depression	6.2% 1/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	16.7% 1/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
Infections and infestations Lymphadenopathy	6.2% 1/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	33.3% 2/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
General disorders Weight gain	0.00% 0/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	16.7% 1/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
Infections and infestations Genital herpes simplex	6.2% 1/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	16.7% 1/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
Infections and infestations Herpes zoster	0.00% 0/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	16.7% 1/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
Skin and subcutaneous tissue disorders Oral ulcer	6.2% 1/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	0.00% 0/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.
Infections and infestations Tooth abscess	6.2% 1/16 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.	0.00% 0/6 • Information on adverse events was collected from the time consent was given to participate in the study through the final study visit at Day 84.