Trial Outcomes & Findings for Safety and Efficacy of Sirolimus for HIV Reservoir Reduction in Individuals on Suppressive Antiretroviral Therapy (ART) (NCT NCT02440789)

NCT ID: NCT02440789

Last Updated: 2021-08-03

Results Overview

The study-defined primary safety endpoint was a composite endpoint. A participant was considered to have met the endpoint if the participant 1) experienced a new Grade ≥3 Adverse Event (AE), including signs/symptoms, lab toxicity or clinical event, that was definitely, probably or possibly related to study treatment, as judged by the core team, or 2) had a change in CD4+ cell count ( confirmed \>50% decline or to \<300 cells/mm3) while on sirolimus. The screening visit occurred within 60 days of study entry.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 32 participants
• Primary outcome timeframe: Screening to study week 32 (week 20 of Sirolimus)
• Results posted on: 2021-08-03

Participant Flow

Participants were recruited at 10 Clinical Research Sites (CRSs) in the United States between December 2015 and March 2017.

Participant milestones

Measure	Sirolimus Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Overall Study STARTED	32
Overall Study Initiated Sirolimus	30
Overall Study Completed 20 Weeks of Sirolimus	16
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure	Sirolimus Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Overall Study Withdrawal by Subject	3
Overall Study Not willing to adhere to reqs	1

Baseline Characteristics

n = 16 participants completed 20 weeks of Sirolimus.

Baseline characteristics by cohort

Measure	Sirolimus n=30 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks. Sirolimus
Age, Continuous Safety Population	52 years n=30 Participants
Sex: Female, Male Female	7 Participants n=30 Participants
Sex: Female, Male Male	23 Participants n=30 Participants
Race/Ethnicity, Customized Race/Ethnicity · White Non-Hispanic	8 Participants n=30 Participants
Race/Ethnicity, Customized Race/Ethnicity · Black Non-Hispanic	18 Participants n=30 Participants
Race/Ethnicity, Customized Race/Ethnicity · Hispanic	3 Participants n=30 Participants
Race/Ethnicity, Customized Race/Ethnicity · More than one race	1 Participants n=30 Participants
Region of Enrollment United States	30 Participants n=30 Participants
CD4+ T-cell counts	818 cells/mm^3 n=30 Participants
HIV-1 Gag-specific CD8+ T-cells by intracellular staining for interferon (IFN)-gamma	0.1 %Gag-specific IFN-gamma+ CD8+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
CD4+ T-cell-associated HIV-1 RNA	2.57 log10(copies/10^6 CD4+ T-cells) n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus
HIV-1 RNA by single-copy assay (SCA) Study Entry · < 0.7 copies/mL	8 Participants n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
HIV-1 RNA by single-copy assay (SCA) Study Entry · >= 0.7 copies/mL	8 Participants n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
HIV-1 RNA by single-copy assay (SCA) Study Week 12 · < 0.7 copies/mL	9 Participants n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
HIV-1 RNA by single-copy assay (SCA) Study Week 12 · >= 0.7 copies/mL	7 Participants n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
HIV-1 RNA Study Entry · < 40 copies/mL	16 Participants n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
HIV-1 RNA Study Entry · >= 40 copies/mL	0 Participants n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
HIV-1 RNA Study Week 12 · < 40 copies/mL	16 Participants n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
HIV-1 RNA Study Week 12 · >= 40 copies/mL	0 Participants n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
HIV-1 Gag-specific CD4+ T-cells by intracellular staining for IFN-gamma	0.04 %Gag-specific IFN-gamma+ CD4+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
GAG-specific CD107a+ CD8+ T-Cells	0.01 %Gag-specific CD107a+ CD8+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
GAG-specific CD107a+ CD4+ T-Cells	0 %Gag-specific CD107a+ CD4+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
GAG-specific CD40L+ CD8+ T-Cells	0.01 %Gag-specific CD40L+CD8+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
GAG-specific CD40L+ CD4+ T-Cells	0.09 %Gag-specific CD40L+CD4+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
GAG-specific interleukin (IL)-2+ CD8+ T-Cells	0.01 %Gag-specific IL-2+ CD8+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
GAG-specific IL-2+ CD4+ T-Cells	0.02 %Gag-specific IL-2+ CD4+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
GAG-specific MIP1B+ CD8+ T-Cells	0.06 %Gag-specific MIP1B+ CD8+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
GAG-specific MIP1B+ CD4+ T-Cells	0.01 %Gag-specific MIP1B+ CD4+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
GAG-specific tumor necrosis factor (TNF)-alpha+ CD8+ T-Cells	0.03 %Gag-specific TNF-alpha CD8+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
GAG-specific TNF-alpha+ CD4+ T-Cells	0.03 %Gag-specific TNF-alpha CD4+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
%CD69+ CD4+ T-cells	5.5 %CD69+ CD4+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
%CD69+ CD8+ T-cells	8.4 %CD69+ CD8+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
%Ki67+ CD4+ T-cells	2.2 %Ki67+ CD4+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
%Ki67+ CD8+ T-cells	1.6 %Ki67+ CD8+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
% programmed cell death protein 1 (PD1)+ CD4+ T-cells	39.7 %PD1+ CD4+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
%PD1+ CD8+ T-cells	27.8 %PD1+ CD8+ T-cells n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.
HIV-1 DNA levels in CD4+ T-cells	2.72 log10(copies/10^6 CD4+ T-cells) n=16 Participants • n = 16 participants completed 20 weeks of Sirolimus.

PRIMARY outcome

Timeframe: Screening to study week 32 (week 20 of Sirolimus)

Population: Participants Initiating Sirolimus.

The study-defined primary safety endpoint was a composite endpoint. A participant was considered to have met the endpoint if the participant 1) experienced a new Grade ≥3 Adverse Event (AE), including signs/symptoms, lab toxicity or clinical event, that was definitely, probably or possibly related to study treatment, as judged by the core team, or 2) had a change in CD4+ cell count ( confirmed >50% decline or to <300 cells/mm3) while on sirolimus. The screening visit occurred within 60 days of study entry.

Outcome measures

Measure	Sirolimus n=30 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Number of Participants Who Met the Study-defined Composite Safety Endpoint	3 Participants

PRIMARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Frequency of HIV-1 Gag-specific CD8+ T-cells by intracellular staining for IFN-gamma. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Efficacy - Immunologic: Frequency of HIV-1 Gag-specific CD8+ T-cells by Intracellular Staining for IFN-gamma Baseline	0.11 %GAG-specific IFN-gamma+ CD8+ T-cells Standard Deviation 0.08
Efficacy - Immunologic: Frequency of HIV-1 Gag-specific CD8+ T-cells by Intracellular Staining for IFN-gamma Week 20 on Sirolimus	0.11 %GAG-specific IFN-gamma+ CD8+ T-cells Standard Deviation 0.07

PRIMARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in HIV-1 Gag-specific CD8+ T-cells by intracellular staining for IFN-gamma (week 32 measurement minus baseline measurement)

Outcome measures

Measure	Sirolimus n=15 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Efficacy - Immunologic: Change in HIV-1 Gag-specific CD8+ T-cells by Intracellular Staining for IFN-gamma	-0.01 %GAG-specific IFN-gamma+ CD8+ T-cells Standard Deviation 0.06

PRIMARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

CD4+ T-cell-associated HIV-1 RNA. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Efficacy - Virologic: CD4+ T-cell-associated HIV-1 RNA Baseline	2.56 log10(copies/10^6 CD4+ T-cells) Standard Deviation 0.67
Efficacy - Virologic: CD4+ T-cell-associated HIV-1 RNA Week 20 on Sirolimus	2.35 log10(copies/10^6 CD4+ T-cells) Standard Deviation 0.68

PRIMARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in CD4+ T-cell-associated HIV-1 RNA (week 32 measurement minus baseline measurement)

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Efficacy - Virologic: Change in CD4+ T-cell-associated HIV-1 RNA	-0.21 log10(copies/10^6 CD4+ T-cells) Standard Deviation 0.48

PRIMARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Plasma HIV-1 RNA by SCA

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Efficacy - Virologic: Plasma HIV-1 RNA by SCA Study week 0 · < 0.7 copies/mL	8 Participants
Efficacy - Virologic: Plasma HIV-1 RNA by SCA Study week 0 · >= 0.7 copies/mL	8 Participants
Efficacy - Virologic: Plasma HIV-1 RNA by SCA Study week 12 · < 0.7 copies/mL	9 Participants
Efficacy - Virologic: Plasma HIV-1 RNA by SCA Study week 12 · >= 0.7 copies/mL	7 Participants
Efficacy - Virologic: Plasma HIV-1 RNA by SCA Study week 32 (week 20 on Sirolimus) · < 0.7 copies/mL	8 Participants
Efficacy - Virologic: Plasma HIV-1 RNA by SCA Study week 32 (week 20 on Sirolimus) · >= 0.7 copies/mL	8 Participants

PRIMARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in plasma HIV-1 RNA by SCA (week 32 measurement minus baseline measurement).

Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Efficacy - Virologic: Change in Plasma HIV-1 RNA by SCA	-0.01 log10(copies/mL) Standard Deviation 0.47

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

CD4+ T-cell counts. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of CD4+ T-cell Counts Baseline	937 cells/mm^3 Standard Deviation 402
Measurement of CD4+ T-cell Counts Study week 16 (week 4 on Sirolimus)	858 cells/mm^3 Standard Deviation 403
Measurement of CD4+ T-cell Counts Study week 24 (week 12 on Sirolimus)	820 cells/mm^3 Standard Deviation 378
Measurement of CD4+ T-cell Counts Study week 32 (week 20 on Sirolimus)	820 cells/mm^3 Standard Deviation 377
Measurement of CD4+ T-cell Counts Study week 44	891 cells/mm^3 Standard Deviation 320

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in CD4+ T-cell counts (week 32 measurement minus baseline measurement)

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in CD4+ T-cell Counts	-118 cells/mm^3 Standard Deviation 211

SECONDARY outcome

Timeframe: weeks 0, 12, (pre-Sirolimus) 16, 24, 32 (4, 12, 20 weeks on Sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

HIV-1 RNA levels by conventional assay

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of HIV-1 RNA Levels Study Week 0 · < 40 copies/mL	16 Participants
Measurement of HIV-1 RNA Levels Study Week 0 · >= 40 copies/mL	0 Participants
Measurement of HIV-1 RNA Levels Study Week 12 · < 40 copies/mL	16 Participants
Measurement of HIV-1 RNA Levels Study Week 12 · >= 40 copies/mL	0 Participants
Measurement of HIV-1 RNA Levels Study Week 16 (Week 4 on Sirolimus) · < 40 copies/mL	16 Participants
Measurement of HIV-1 RNA Levels Study Week 16 (Week 4 on Sirolimus) · >= 40 copies/mL	0 Participants
Measurement of HIV-1 RNA Levels Study Week 24 (Week 12 on Sirolimus) · < 40 copies/mL	16 Participants
Measurement of HIV-1 RNA Levels Study Week 24 (Week 12 on Sirolimus) · >= 40 copies/mL	0 Participants
Measurement of HIV-1 RNA Levels Study Week 32 (Week 20 on Sirolimus) · < 40 copies/mL	16 Participants
Measurement of HIV-1 RNA Levels Study Week 32 (Week 20 on Sirolimus) · >= 40 copies/mL	0 Participants
Measurement of HIV-1 RNA Levels Study Week 44 · < 40 copies/mL	16 Participants
Measurement of HIV-1 RNA Levels Study Week 44 · >= 40 copies/mL	0 Participants

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

HIV-1 DNA levels in CD4+ T-cells. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Cell-associated HIV-1 DNA Levels in Total CD4+ Cells Baseline	2.65 log10(copies/10^6 CD4+ T-cells) Standard Deviation 0.71
Cell-associated HIV-1 DNA Levels in Total CD4+ Cells Study week 16 (week 4 on Sirolimus)	2.45 log10(copies/10^6 CD4+ T-cells) Standard Deviation 0.81
Cell-associated HIV-1 DNA Levels in Total CD4+ Cells Study week 24 (week 12 on Sirolimus)	2.48 log10(copies/10^6 CD4+ T-cells) Standard Deviation 0.78
Cell-associated HIV-1 DNA Levels in Total CD4+ Cells Study week 32 (week 20 on Sirolimus)	2.49 log10(copies/10^6 CD4+ T-cells) Standard Deviation 0.75
Cell-associated HIV-1 DNA Levels in Total CD4+ Cells Study week 44	2.51 log10(copies/10^6 CD4+ T-cells) Standard Deviation 0.79

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in HIV-1 DNA levels in CD4+ T-cells (week 32 measurement minus baseline measurement)

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in Cell-associated HIV-1 DNA Levels in Total CD4+ Cells	-0.16 log10(copies/10^6 CD4+ T-cells) Standard Deviation 0.21

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

Frequency of HIV-1 Gag-specific CD107a+ CD8+ T-cells. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of HIV-1 Gag-specific CD107a+ CD8+ T-cell Responses Baseline	0.01 %Gag-specific CD107a+ CD8+ T-cells Standard Deviation 0.01
Measurement of HIV-1 Gag-specific CD107a+ CD8+ T-cell Responses Study week 16 (week 4 on Sirolimus)	0.02 %Gag-specific CD107a+ CD8+ T-cells Standard Deviation 0.02
Measurement of HIV-1 Gag-specific CD107a+ CD8+ T-cell Responses Study week 24 (week 12 on Sirolimus)	0.01 %Gag-specific CD107a+ CD8+ T-cells Standard Deviation 0.01
Measurement of HIV-1 Gag-specific CD107a+ CD8+ T-cell Responses Study week 32 (week 20 on Sirolimus)	0.05 %Gag-specific CD107a+ CD8+ T-cells Standard Deviation 0.14
Measurement of HIV-1 Gag-specific CD107a+ CD8+ T-cell Responses Study week 44	0.02 %Gag-specific CD107a+ CD8+ T-cells Standard Deviation 0.03

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in frequency of HIV-1 Gag-specific CD107a+ CD8+ T-cells (week 32 measurement minus baseline measurement)

Outcome measures

Measure	Sirolimus n=15 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in HIV-1 Gag-specific CD107a+ CD8+ T-cell Responses	0.04 %Gag-specific CD107a+ CD8+ T-cells Standard Deviation 0.14

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

Frequency of HIV-1 Gag-specific CD40L+ CD8+ T-cells. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of HIV-1 Gag-specific CD40L+ CD8+ T-cell Responses Baseline	0.02 %Gag-specific CD40L+ CD8+ T-cells Standard Deviation 0.02
Measurement of HIV-1 Gag-specific CD40L+ CD8+ T-cell Responses Study week 16 (week 4 on Sirolimus)	1.15 %Gag-specific CD40L+ CD8+ T-cells Standard Deviation 4.53
Measurement of HIV-1 Gag-specific CD40L+ CD8+ T-cell Responses Study week 24 (week 12 on Sirolimus)	0.01 %Gag-specific CD40L+ CD8+ T-cells Standard Deviation 0.03
Measurement of HIV-1 Gag-specific CD40L+ CD8+ T-cell Responses Study week 32 (week 20 on Sirolimus)	0.03 %Gag-specific CD40L+ CD8+ T-cells Standard Deviation 0.05
Measurement of HIV-1 Gag-specific CD40L+ CD8+ T-cell Responses Study week 44	0.01 %Gag-specific CD40L+ CD8+ T-cells Standard Deviation 0.02

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in frequency of HIV-1 Gag-specific CD40L+ CD8+ T-cells (week 32 measurement minus baseline measurement)

Outcome measures

Measure	Sirolimus n=15 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in HIV-1 Gag-specific CD40L+ CD8+ T-cell Responses	0.01 %Gag-specific CD40L+ CD8+ T-cells Standard Deviation 0.06

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

Frequency of HIV-1 Gag-specific IL-2+ CD8+ T-cells. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of HIV-1 Gag-specific IL-2+ CD8+ T-cell Responses Baseline	0.02 %Gag-specific IL-2+ CD8+ T-cells Standard Deviation 0.03
Measurement of HIV-1 Gag-specific IL-2+ CD8+ T-cell Responses Study week 16 (week 4 on Sirolimus)	0.01 %Gag-specific IL-2+ CD8+ T-cells Standard Deviation 0.02
Measurement of HIV-1 Gag-specific IL-2+ CD8+ T-cell Responses Study week 24 (week 12 on Sirolimus)	0.02 %Gag-specific IL-2+ CD8+ T-cells Standard Deviation 0.02
Measurement of HIV-1 Gag-specific IL-2+ CD8+ T-cell Responses Study week 32 (week 20 on Sirolimus)	0.02 %Gag-specific IL-2+ CD8+ T-cells Standard Deviation 0.03
Measurement of HIV-1 Gag-specific IL-2+ CD8+ T-cell Responses Study week 44	0.03 %Gag-specific IL-2+ CD8+ T-cells Standard Deviation 0.04

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in frequency of HIV-1 Gag-specific IL-2+ CD8+ T-cells (week 32 measurement minus baseline measurement)

Outcome measures

Measure	Sirolimus n=15 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in HIV-1 Gag-specific IL-2+ CD8+ T-cell Responses	0 %Gag-specific IL-2+ CD8+ T-cells Standard Deviation 0.05

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

Frequency of HIV-1 Gag-specific MIP1B+ CD8+ T-cells. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of HIV-1 Gag-specific MIP1B+ CD8+ T-cell Responses Baseline	0.09 %GAG-specific MIP1B+ CD8+ T-Cells Standard Deviation 0.08
Measurement of HIV-1 Gag-specific MIP1B+ CD8+ T-cell Responses Study week 16 (week 4 on Sirolimus)	0.51 %GAG-specific MIP1B+ CD8+ T-Cells Standard Deviation 1.72
Measurement of HIV-1 Gag-specific MIP1B+ CD8+ T-cell Responses Study week 24 (week 12 on Sirolimus)	0.08 %GAG-specific MIP1B+ CD8+ T-Cells Standard Deviation 0.08
Measurement of HIV-1 Gag-specific MIP1B+ CD8+ T-cell Responses Study week 32 (week 20 on Sirolimus)	0.09 %GAG-specific MIP1B+ CD8+ T-Cells Standard Deviation 0.08
Measurement of HIV-1 Gag-specific MIP1B+ CD8+ T-cell Responses Study week 44	0.08 %GAG-specific MIP1B+ CD8+ T-Cells Standard Deviation 0.1

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in frequency of HIV-1 Gag-specific MIP1B+ CD8+ T-cells (week 32 measurement minus baseline measurement)

Outcome measures

Measure	Sirolimus n=15 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in HIV-1 Gag-specific MIP1B+ CD8+ T-cell Responses	-0.01 %GAG-specific MIP1B+ CD8+ T-Cells Standard Deviation 0.06

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

Frequency of HIV-1 Gag-specific TNF-alpha+ CD8+ T-cells. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of HIV-1 Gag-specific TNF-alpha+ CD8+ T-cell Responses Baseline	0.04 %GAG-specific TNF-a+ CD8+ T-Cells Standard Deviation 0.03
Measurement of HIV-1 Gag-specific TNF-alpha+ CD8+ T-cell Responses Study week 16 (week 4 on Sirolimus)	0.04 %GAG-specific TNF-a+ CD8+ T-Cells Standard Deviation 0.03
Measurement of HIV-1 Gag-specific TNF-alpha+ CD8+ T-cell Responses Study week 24 (week 12 on Sirolimus)	0.03 %GAG-specific TNF-a+ CD8+ T-Cells Standard Deviation 0.02
Measurement of HIV-1 Gag-specific TNF-alpha+ CD8+ T-cell Responses Study week 32 (week 20 on Sirolimus)	0.05 %GAG-specific TNF-a+ CD8+ T-Cells Standard Deviation 0.05
Measurement of HIV-1 Gag-specific TNF-alpha+ CD8+ T-cell Responses Study week 44	0.04 %GAG-specific TNF-a+ CD8+ T-Cells Standard Deviation 0.04

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in frequency of HIV-1 Gag-specific TNF-alpha+ CD8+ T-cells (week 32 measurement minus baseline measurement)

Outcome measures

Measure	Sirolimus n=15 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in HIV-1 Gag-specific TNF-alpha+ CD8+ T-cell Responses	0.01 %GAG-specific TNF-a+ CD8+ T-Cells Standard Deviation 0.04

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

Frequency of HIV-1 Gag-specific CD4+ T-cells by intracellular staining for IFN-gamma. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of HIV-1 Gag-specific CD4+ T-cell by Intracellular Staining for IFN-gamma Responses Baseline	0.06 %GAG-specific IFN-g+ CD4+ T-Cells Standard Deviation 0.06
Measurement of HIV-1 Gag-specific CD4+ T-cell by Intracellular Staining for IFN-gamma Responses Study week 16 (week 4 on Sirolimus)	0.04 %GAG-specific IFN-g+ CD4+ T-Cells Standard Deviation 0.03
Measurement of HIV-1 Gag-specific CD4+ T-cell by Intracellular Staining for IFN-gamma Responses Study week 24 (week 12 on Sirolimus)	0.05 %GAG-specific IFN-g+ CD4+ T-Cells Standard Deviation 0.06
Measurement of HIV-1 Gag-specific CD4+ T-cell by Intracellular Staining for IFN-gamma Responses Study week 32 (week 20 on Sirolimus)	0.06 %GAG-specific IFN-g+ CD4+ T-Cells Standard Deviation 0.05
Measurement of HIV-1 Gag-specific CD4+ T-cell by Intracellular Staining for IFN-gamma Responses Study week 44	0.04 %GAG-specific IFN-g+ CD4+ T-Cells Standard Deviation 0.04

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in HIV-1 Gag-specific CD4+ T-cells by intracellular staining for IFN-gamma (week 32 measurement minus baseline measurement)

Outcome measures

Measure	Sirolimus n=15 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in HIV-1 Gag-specific CD4+ T-cell by Intracellular Staining for IFN-gamma Responses	0 %GAG-specific IFN-g+ CD4+ T-Cells Standard Deviation 0.04

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

Frequency of HIV-1 Gag-specific CD107a+ CD4+ T-cells. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of HIV-1 Gag-specific CD107a+ CD4+ T-cell Responses Baseline	0.01 %GAG-specific CD107a+ CD4+ T-Cells Standard Deviation 0.01
Measurement of HIV-1 Gag-specific CD107a+ CD4+ T-cell Responses Study week 16 (week 4 on Sirolimus)	0.01 %GAG-specific CD107a+ CD4+ T-Cells Standard Deviation 0.01
Measurement of HIV-1 Gag-specific CD107a+ CD4+ T-cell Responses Study week 24 (week 12 on Sirolimus)	0.01 %GAG-specific CD107a+ CD4+ T-Cells Standard Deviation 0.01
Measurement of HIV-1 Gag-specific CD107a+ CD4+ T-cell Responses Study week 32 (week 20 on Sirolimus)	0.03 %GAG-specific CD107a+ CD4+ T-Cells Standard Deviation 0.08
Measurement of HIV-1 Gag-specific CD107a+ CD4+ T-cell Responses Study week 44	0.02 %GAG-specific CD107a+ CD4+ T-Cells Standard Deviation 0.02

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in frequency of HIV-1 Gag-specific CD107a+ CD4+ T-cells (week 32 measurement minus baseline measurement)

Outcome measures

Measure	Sirolimus n=15 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in HIV-1 Gag-specific CD107a+ CD4+ T-cell Responses	0.02 %GAG-specific CD107a+ CD4+ T-Cells Standard Deviation 0.08

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

Frequency of HIV-1 Gag-specific CD40L+ CD4+ T-cells. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of HIV-1 Gag-specific CD40L+ CD4+ T-cell Responses Baseline	0.08 %GAG-specific CD40L+ CD4+ T-Cells Standard Deviation 0.05
Measurement of HIV-1 Gag-specific CD40L+ CD4+ T-cell Responses Study week 16 (week 4 on Sirolimus)	0.06 %GAG-specific CD40L+ CD4+ T-Cells Standard Deviation 0.06
Measurement of HIV-1 Gag-specific CD40L+ CD4+ T-cell Responses Study week 24 (week 12 on Sirolimus)	0.1 %GAG-specific CD40L+ CD4+ T-Cells Standard Deviation 0.06
Measurement of HIV-1 Gag-specific CD40L+ CD4+ T-cell Responses Study week 32 (week 20 on Sirolimus)	0.08 %GAG-specific CD40L+ CD4+ T-Cells Standard Deviation 0.07
Measurement of HIV-1 Gag-specific CD40L+ CD4+ T-cell Responses Study week 44	0.08 %GAG-specific CD40L+ CD4+ T-Cells Standard Deviation 0.07

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in frequency of HIV-1 Gag-specific CD40L+ CD4+ T-cells (week 32 measurement minus baseline measurement).

Outcome measures

Measure	Sirolimus n=15 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in HIV-1 Gag-specific CD40L+ CD4+ T-cell Responses	-0.01 %GAG-specific CD40L+ CD4+ T-Cells Standard Deviation 0.07

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

Frequency of HIV-1 Gag-specific IL-2+ CD4+ T-cells. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of HIV-1 Gag-specific IL-2+ CD4+ T-cell Responses Baseline	0.03 %GAG-specific IL-2+ CD4+ T-Cells Standard Deviation 0.05
Measurement of HIV-1 Gag-specific IL-2+ CD4+ T-cell Responses Study week 16 (week 4 on Sirolimus)	0.04 %GAG-specific IL-2+ CD4+ T-Cells Standard Deviation 0.03
Measurement of HIV-1 Gag-specific IL-2+ CD4+ T-cell Responses Study week 24 (week 12 on Sirolimus)	0.04 %GAG-specific IL-2+ CD4+ T-Cells Standard Deviation 0.07
Measurement of HIV-1 Gag-specific IL-2+ CD4+ T-cell Responses Study week 32 (week 20 on Sirolimus)	0.08 %GAG-specific IL-2+ CD4+ T-Cells Standard Deviation 0.16
Measurement of HIV-1 Gag-specific IL-2+ CD4+ T-cell Responses Study week 44	0.04 %GAG-specific IL-2+ CD4+ T-Cells Standard Deviation 0.05

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in frequency of HIV-1 Gag-specific IL-2+ CD4+ T-cells (week 32 measurement minus baseline measurement)

Outcome measures

Measure	Sirolimus n=15 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in HIV-1 Gag-specific IL-2+ CD4+ T-cell Responses	0.04 %GAG-specific IL-2+ CD4+ T-Cells Standard Deviation 0.15

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

Frequency of HIV-1 Gag-specific MIP1B+ CD4+ T-cells. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of HIV-1 Gag-specific MIP1B+ CD4+ T-cell Responses Baseline	0.01 %GAG-specific MIP1B+ CD4+ T-Cells Standard Deviation 0.01
Measurement of HIV-1 Gag-specific MIP1B+ CD4+ T-cell Responses Study week 16 (week 4 on Sirolimus)	0.01 %GAG-specific MIP1B+ CD4+ T-Cells Standard Deviation 0.01
Measurement of HIV-1 Gag-specific MIP1B+ CD4+ T-cell Responses Study week 24 (week 12 on Sirolimus)	0.01 %GAG-specific MIP1B+ CD4+ T-Cells Standard Deviation 0.02
Measurement of HIV-1 Gag-specific MIP1B+ CD4+ T-cell Responses Study week 32 (week 20 on Sirolimus)	0.01 %GAG-specific MIP1B+ CD4+ T-Cells Standard Deviation 0.01
Measurement of HIV-1 Gag-specific MIP1B+ CD4+ T-cell Responses Study week 44	0.01 %GAG-specific MIP1B+ CD4+ T-Cells Standard Deviation 0.01

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in frequency of HIV-1 Gag-specific MIP1B+ CD4+ T-cells (week 32 measurement minus baseline measurement).

Outcome measures

Measure	Sirolimus n=15 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in HIV-1 Gag-specific MIP1B+ CD4+ T-cell Responses	0 %GAG-specific MIP1B+ CD4+ T-Cells Standard Deviation 0.01

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

Frequency of HIV-1 Gag-specific TNF-alpha+ CD4+ T-cells. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of HIV-1 Gag-specific TNF-alpha+ CD4+ T-cell Responses Baseline	0.04 %GAG-specific TNF-alpha+ CD4+ T-Cells Standard Deviation 0.03
Measurement of HIV-1 Gag-specific TNF-alpha+ CD4+ T-cell Responses Study week 16 (week 4 on Sirolimus)	0.04 %GAG-specific TNF-alpha+ CD4+ T-Cells Standard Deviation 0.03
Measurement of HIV-1 Gag-specific TNF-alpha+ CD4+ T-cell Responses Study week 24 (week 12 on Sirolimus)	0.03 %GAG-specific TNF-alpha+ CD4+ T-Cells Standard Deviation 0.04
Measurement of HIV-1 Gag-specific TNF-alpha+ CD4+ T-cell Responses Study week 32 (week 20 on Sirolimus)	0.04 %GAG-specific TNF-alpha+ CD4+ T-Cells Standard Deviation 0.03
Measurement of HIV-1 Gag-specific TNF-alpha+ CD4+ T-cell Responses Study week 44	0.04 %GAG-specific TNF-alpha+ CD4+ T-Cells Standard Deviation 0.03

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in frequency of HIV-1 Gag-specific TNF-alpha+ CD4+ T-cells (week 32 measurement minus baseline measurement).

Outcome measures

Measure	Sirolimus n=15 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in HIV-1 Gag-specific TNF-alpha+ CD4+ T-cell Responses	0 %GAG-specific TNF-alpha+ CD4+ T-Cells Standard Deviation 0.02

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

Measurement of %CD69+ CD4+ T-cells. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of %CD69+ CD4+ T-cells Baseline	6.3 %CD69+ CD4+ T-Cells Standard Deviation 2.6
Measurement of %CD69+ CD4+ T-cells Study week 16 (week 4 on Sirolimus)	6.1 %CD69+ CD4+ T-Cells Standard Deviation 2.3
Measurement of %CD69+ CD4+ T-cells Study week 24 (week 12 on Sirolimus)	5.8 %CD69+ CD4+ T-Cells Standard Deviation 2.0
Measurement of %CD69+ CD4+ T-cells Study week 32 (week 20 on Sirolimus)	6.1 %CD69+ CD4+ T-Cells Standard Deviation 1.9
Measurement of %CD69+ CD4+ T-cells Study week 44	5.9 %CD69+ CD4+ T-Cells Standard Deviation 2.3

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in of %CD69+ CD4+ T-cells (week 32 measurement minus baseline measurement).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in of %CD69+ CD4+ T-cells	-0.17 %CD69+ CD4+ T-Cells Standard Deviation 1.51

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

Measurement of %CD69+ CD8+ T-cells. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of %CD69+ CD8+ T-cells Baseline	8.6 %CD69+ CD8+ T-Cells Standard Deviation 2.9
Measurement of %CD69+ CD8+ T-cells Study week 16 (week 4 on Sirolimus)	8.4 %CD69+ CD8+ T-Cells Standard Deviation 2.8
Measurement of %CD69+ CD8+ T-cells Study week 24 (week 12 on Sirolimus)	7.9 %CD69+ CD8+ T-Cells Standard Deviation 2.5
Measurement of %CD69+ CD8+ T-cells Study week 32 (week 20 on Sirolimus)	8.1 %CD69+ CD8+ T-Cells Standard Deviation 2.5
Measurement of %CD69+ CD8+ T-cells Study week 44	8.2 %CD69+ CD8+ T-Cells Standard Deviation 2.4

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in of %CD69+ CD8+ T-cells (week 32 measurement minus baseline measurement)

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in of %CD69+ CD8+ T-cells	-0.52 %CD69+ CD8+ T-Cells Standard Deviation 1.63

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

Measurement of %Ki67+ CD4+ T-cells. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of %Ki67+ CD4+ T-cells Baseline	2.4 %Ki67+ CD4+ T-Cells Standard Deviation 0.8
Measurement of %Ki67+ CD4+ T-cells Study week 16 (week 4 on Sirolimus)	2.2 %Ki67+ CD4+ T-Cells Standard Deviation 0.9
Measurement of %Ki67+ CD4+ T-cells Study week 24 (week 12 on Sirolimus)	2.2 %Ki67+ CD4+ T-Cells Standard Deviation 0.8
Measurement of %Ki67+ CD4+ T-cells Study week 32 (week 20 on Sirolimus)	1.9 %Ki67+ CD4+ T-Cells Standard Deviation 0.8
Measurement of %Ki67+ CD4+ T-cells Study week 44	2.4 %Ki67+ CD4+ T-Cells Standard Deviation 1

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in of %Ki67+ CD4+ T-cells (week 32 measurement minus baseline measurement).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in of %Ki67+ CD4+ T-cells	-0.51 %Ki67+ CD4+ T-Cells Standard Deviation 0.86

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

Measurement of %Ki67+ CD8+ T-cells. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of %Ki67+ CD8+ T-cells Baseline	1.8 %Ki67+ CD8+ T-Cells Standard Deviation 0.8
Measurement of %Ki67+ CD8+ T-cells Study week 16 (week 4 on Sirolimus)	1 %Ki67+ CD8+ T-Cells Standard Deviation 0.4
Measurement of %Ki67+ CD8+ T-cells Study week 24 (week 12 on Sirolimus)	1.4 %Ki67+ CD8+ T-Cells Standard Deviation 0.7
Measurement of %Ki67+ CD8+ T-cells Study week 32 (week 20 on Sirolimus)	1.2 %Ki67+ CD8+ T-Cells Standard Deviation 0.6
Measurement of %Ki67+ CD8+ T-cells Study week 44	1.7 %Ki67+ CD8+ T-Cells Standard Deviation 0.7

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in of %Ki67+ CD8+ T-cells (week 32 measurement minus baseline measurement)

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in of %Ki67+ CD8+ T-cells	-0.54 %Ki67+ CD8+ T-Cells Standard Deviation 0.67

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

Measurement of %PD1+ CD4+ T-cells. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of %PD1+ CD4+ T-cells Baseline	38.4 %PD1+ CD4+ T-Cells Standard Deviation 9.6
Measurement of %PD1+ CD4+ T-cells Study week 16 (week 4 on Sirolimus)	39 %PD1+ CD4+ T-Cells Standard Deviation 11.1
Measurement of %PD1+ CD4+ T-cells Study week 24 (week 12 on Sirolimus)	38.8 %PD1+ CD4+ T-Cells Standard Deviation 10.7
Measurement of %PD1+ CD4+ T-cells Study week 32 (week 20 on Sirolimus)	38.8 %PD1+ CD4+ T-Cells Standard Deviation 9.9
Measurement of %PD1+ CD4+ T-cells Study week 44	35.5 %PD1+ CD4+ T-Cells Standard Deviation 10.6

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in of %PD1+ CD4+ T-cells (week 32 measurement minus baseline measurement)

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in of %PD1+ CD4+ T-cells	0.42 %PD1+ CD4+ T-Cells Standard Deviation 4.19

SECONDARY outcome

Timeframe: At study weeks 0, 12, 16, 24, 32 (4, 12, 20 weeks on sirolimus) and 44

Population: Participants completing 20 weeks of Sirolimus

Measurement of %PD1+ CD8+ T-cells. Baseline is the mean of the two pre-Sirolimus measurements (study entry and study week 12).

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Measurement of %PD1+ CD8+ T-cells Baseline	29.4 %PD1+ CD8+ T-Cells Standard Deviation 10.2
Measurement of %PD1+ CD8+ T-cells Study week 16 (week 4 on Sirolimus)	28.4 %PD1+ CD8+ T-Cells Standard Deviation 9.9
Measurement of %PD1+ CD8+ T-cells Study week 24 (week 12 on Sirolimus)	28.4 %PD1+ CD8+ T-Cells Standard Deviation 10.6
Measurement of %PD1+ CD8+ T-cells Study week 32 (week 20 on Sirolimus)	26.6 %PD1+ CD8+ T-Cells Standard Deviation 9.9
Measurement of %PD1+ CD8+ T-cells Study week 44	25.5 %PD1+ CD8+ T-Cells Standard Deviation 8.7

SECONDARY outcome

Timeframe: At study weeks 0, 12 and 32 (week 20 on Sirolimus)

Population: Participants completing 20 weeks of Sirolimus

Change in of %PD1+ CD8+ T-cells (week 32 measurement minus baseline measurement)

Outcome measures

Measure	Sirolimus n=16 Participants Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Change in of %PD1+ CD8+ T-cells	-2.85 %PD1+ CD8+ T-Cells Standard Deviation 3.74

Adverse Events

Sirolimus

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Measure

Sirolimus n=30 participants at risk Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.

Gastrointestinal disorders Diarrhoea

3.3% 1/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.

Other adverse events

Measure	Sirolimus n=30 participants at risk Participants on a non-protease inhibitor (PI), non-non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen, and for those on a non-PI, rilpivirine (RPV) based regimen received 0.025 mg/kg/day initial dose for 20 weeks. Participants on an NNRTI regimen with the exception of RPV received 0.05 mg/kg/day initial dose for 20 weeks.
Gastrointestinal disorders Diarrhoea	10.0% 3/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Gastrointestinal disorders Mouth ulceration	6.7% 2/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
General disorders Asthenia	6.7% 2/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
General disorders Chills	6.7% 2/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
General disorders Fatigue	10.0% 3/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
General disorders Malaise	10.0% 3/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
General disorders Pain	10.0% 3/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
General disorders Pyrexia	6.7% 2/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Infections and infestations Viral upper respiratory tract infection	10.0% 3/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Investigations Alanine aminotransferase increased	10.0% 3/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Investigations Aspartate aminotransferase increased	23.3% 7/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Investigations Blood alkaline phosphatase increased	10.0% 3/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Investigations Blood cholesterol increased	50.0% 15/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Investigations Blood creatine phosphokinase increased	16.7% 5/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Investigations Blood creatinine increased	10.0% 3/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Investigations Blood glucose decreased	10.0% 3/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Investigations Blood glucose increased	43.3% 13/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Investigations Blood pressure increased	6.7% 2/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Investigations Blood sodium decreased	10.0% 3/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Investigations Blood sodium increased	6.7% 2/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Investigations Blood triglycerides increased	60.0% 18/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Investigations Low density lipoprotein increased	43.3% 13/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Investigations Weight decreased	6.7% 2/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Metabolism and nutrition disorders Decreased appetite	10.0% 3/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Musculoskeletal and connective tissue disorders Joint swelling	6.7% 2/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Renal and urinary disorders Pollakiuria	6.7% 2/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Respiratory, thoracic and mediastinal disorders Cough	13.3% 4/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.7% 2/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Respiratory, thoracic and mediastinal disorders Nasal congestion	6.7% 2/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Respiratory, thoracic and mediastinal disorders Productive cough	6.7% 2/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	10.0% 3/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.
Skin and subcutaneous tissue disorders Night sweats	6.7% 2/30 • Screening to study week 32 (week 20 of Sirolimus) At entry, all grades of signs and symptoms that occurred within 30 days before entry were recorded; post-entry, all grades of Grade ≥2 were recorded. All Grade 3 or higher sign/symptom, any sign/symptom regardless of grade that led to a change in study treatment, or that met ICH, EAE or SAE guidelines were recorded. The DAIDS AE Grading Table Version 2.0 and Expedited AE Manual Version 2.0 were used. All participants exposed to Sirolimus are included.

Additional Information

ACTG Clinicaltrials.gov Coordinator

ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

Phone: (301) 628-3313

Email: ACTGCT.Gov@s-3.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place