Trial Outcomes & Findings for Effect of Isotretinoin on Immune Activation Among HIV-1 Infected Subjects With Incomplete CD4+ T Cell Recovery (NCT NCT01969058)

NCT ID: NCT01969058

Last Updated: 2024-10-15

Results Overview

Level of CD8+ T-cell activation was determined by measuring the percentage of CD8+ T-cells that expressed both the activation marker CD38+ and Human leukocyte antigen (HLA)-DR+. The endpoint is measuring the change from baseline to week 14/16, where baseline is defined as the average of pre-entry and entry, and week 14/16 is defined as the average of week 14 and week 16. Change = (week 14/16 - baseline).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 76 participants
• Primary outcome timeframe: baseline, week 14/16
• Results posted on: 2024-10-15

Participant Flow

First participant was enrolled on July 2, 2014. Accrual to the study closed on May 5, 2016, with 15 U.S and Puerto Rico sites registered and enrolled participants

Participants were randomized 2:1 to Isotretinoin and no study treatment arms. Randomization was stratified by willingness to participate in the gut biopsy substudy, A5330s.

Participant milestones

Measure	Isotretinoin Arm Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm No Isotretinoin treatment
Overall Study STARTED	50	26
Overall Study COMPLETED	47	26
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Measure	Isotretinoin Arm Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm No Isotretinoin treatment
Overall Study Withdrawal by Subject	2	0
Overall Study Adverse Event	1	0

Baseline Characteristics

The primary endpoint is limited to participants who have data for both baseline and week 14/16, (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses), did not use prohibited medications, and did not experience virologic failure from baseline to week 16.

Baseline characteristics by cohort

Measure	Isotretinoin Arm n=50 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment	Total n=76 Participants Total of all reporting groups
Age, Continuous	49 years n=50 Participants	51 years n=26 Participants	49 years n=76 Participants
Age, Customized 18-39 years	14 Participants n=50 Participants	7 Participants n=26 Participants	21 Participants n=76 Participants
Age, Customized 40-59 years	31 Participants n=50 Participants	16 Participants n=26 Participants	47 Participants n=76 Participants
Age, Customized >=60 years	5 Participants n=50 Participants	3 Participants n=26 Participants	8 Participants n=76 Participants
Sex: Female, Male Female	4 Participants n=50 Participants	1 Participants n=26 Participants	5 Participants n=76 Participants
Sex: Female, Male Male	46 Participants n=50 Participants	25 Participants n=26 Participants	71 Participants n=76 Participants
Race/Ethnicity, Customized Non-Hispanic White	18 Participants n=50 Participants	12 Participants n=26 Participants	30 Participants n=76 Participants
Race/Ethnicity, Customized Non-Hispanic Black	21 Participants n=50 Participants	9 Participants n=26 Participants	30 Participants n=76 Participants
Race/Ethnicity, Customized Hispanic (Regardless of Race)	11 Participants n=50 Participants	5 Participants n=26 Participants	16 Participants n=76 Participants
Region of Enrollment Puerto Rico	1 Participants n=50 Participants	0 Participants n=26 Participants	1 Participants n=76 Participants
Region of Enrollment United States	49 Participants n=50 Participants	26 Participants n=26 Participants	75 Participants n=76 Participants
HIV-1 RNA >= Assay lower limit (40 copies/mL)	0 Participants n=50 Participants	1 Participants n=26 Participants	1 Participants n=76 Participants
HIV-1 RNA < Assay lower limit (40 copies/mL)	50 Participants n=50 Participants	25 Participants n=26 Participants	75 Participants n=76 Participants
CD4+ Cell Count	549 cells/mm^3 n=50 Participants	556 cells/mm^3 n=26 Participants	552 cells/mm^3 n=76 Participants
BMI	27.1 kg/m^2 n=50 Participants	26.9 kg/m^2 n=26 Participants	27.1 kg/m^2 n=76 Participants
CD8+ T-cell Activation Percent	13.67 percentage of cells n=39 Participants • The primary endpoint is limited to participants who have data for both baseline and week 14/16, (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses), did not use prohibited medications, and did not experience virologic failure from baseline to week 16.	13.40 percentage of cells n=26 Participants • The primary endpoint is limited to participants who have data for both baseline and week 14/16, (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses), did not use prohibited medications, and did not experience virologic failure from baseline to week 16.	13.66 percentage of cells n=65 Participants • The primary endpoint is limited to participants who have data for both baseline and week 14/16, (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses), did not use prohibited medications, and did not experience virologic failure from baseline to week 16.

PRIMARY outcome

Timeframe: baseline, week 14/16

Population: The primary analysis is complete case as-treated, and is limited to participants who: * have data for both baseline and week 14/16 * (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses) * did not use prohibited medications * did not experience virologic failure from baseline to week 16

Level of CD8+ T-cell activation was determined by measuring the percentage of CD8+ T-cells that expressed both the activation marker CD38+ and Human leukocyte antigen (HLA)-DR+. The endpoint is measuring the change from baseline to week 14/16, where baseline is defined as the average of pre-entry and entry, and week 14/16 is defined as the average of week 14 and week 16.

Change = (week 14/16 - baseline).

Outcome measures

Measure	Isotretinoin Arm n=39 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment
Change in CD8+ T-cell Activation From Baseline to Week 14/16	3.24 percentage of cells Interval 0.77 to 7.75	0.52 percentage of cells Interval -0.41 to 2.86

SECONDARY outcome

Timeframe: baseline, week 14/16, week 28

Population: The analysis is complete case as-treated, and is limited to participants who: * have data for both baseline and week 14/16 * (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses) * did not use prohibited medications * did not experience virologic failure from baseline to week 16

Level of CD8+ T-cell activation was determined by measuring the percentage of CD8+ T-cells that expressed both the activation marker CD38+ and Human leukocyte antigen (HLA)-DR+.

The endpoint is measuring the change from week 14/16 to week 28 (week 28 - week 14/16) and from baseline to week 28 (week 28 - baseline).

Baseline is defined as the average of pre-entry and entry, and week 14/16 is defined as the average of week 14 and week 16.

Outcome measures

Measure	Isotretinoin Arm n=39 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment
Change in CD8+ T-cell Activation Change from week 14/16 to week 28	-3.58 percentage of cells Interval -8.45 to 0.35	-0.91 percentage of cells Interval -3.4 to 1.49
Change in CD8+ T-cell Activation Change from baseline to week 28	-0.69 percentage of cells Interval -2.61 to 4.0	0.03 percentage of cells Interval -2.34 to 3.32

SECONDARY outcome

Timeframe: baseline, week 14/16, week 28

Population: The analysis is complete case as-treated, and is limited to participants who: * have data for both baseline and week 14/16 * (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses) * did not use prohibited medications * did not experience virologic failure from baseline to week 16

sCD14 (soluble cluster of differentiation 14) is a marker of gut microbial translocation and monocyte activation.

The outcome measures are changes in log10 transformed sCD14 from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).

Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.

Outcome measures

Measure	Isotretinoin Arm n=39 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment
Change in sCD14 Change from baseline to week 14/16	0.02 log10 pg/mL Interval -0.03 to 0.1	-0.02 log10 pg/mL Interval -0.06 to 0.05
Change in sCD14 Change from week 14/16 to week 28	-0.06 log10 pg/mL Interval -0.13 to 0.02	0.02 log10 pg/mL Interval -0.04 to 0.06
Change in sCD14 Change from baseline to week 28	-0.02 log10 pg/mL Interval -0.07 to 0.05	0.00 log10 pg/mL Interval -0.06 to 0.05

SECONDARY outcome

Timeframe: baseline, week 14/16, week 28

Population: The analysis is complete case as-treated, and is limited to participants who: * have data for both baseline and week 14/16 * (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses) * did not use prohibited medications * did not experience virologic failure from baseline to week 16

I-FABP (intestinal-fatty acid binding protein) is a marker of intestinal cell damage and turnover.

The outcome measures are changes in log10 transformed I-FABP from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).

Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.

Outcome measures

Measure	Isotretinoin Arm n=39 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment
Change in I-FABP Change from baseline to week 14/16	-0.03 log10 pg/mL Interval -0.14 to 0.1	0.04 log10 pg/mL Interval -0.05 to 0.17
Change in I-FABP Change from week 14/16 to week 28	0.09 log10 pg/mL Interval -0.01 to 0.16	-0.05 log10 pg/mL Interval -0.15 to 0.05
Change in I-FABP Change from baseline to week 28	0.07 log10 pg/mL Interval -0.05 to 0.2	-0.07 log10 pg/mL Interval -0.19 to 0.11

SECONDARY outcome

Timeframe: baseline, week 14/16, week 28

Population: The analysis is complete case as-treated, and is limited to participants who: * have data for both baseline and week 14/16 * (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses) * did not use prohibited medications * did not experience virologic failure from baseline to week 16

IL-6 (Interleukin-6) is a marker of systemic inflammation. The outcome measures are changes in log10 transformed IL-6 from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).

Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.

Outcome measures

Measure	Isotretinoin Arm n=39 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment
Change in IL-6 Change from baseline to week 14/16	0.10 log10 pg/mL Interval -0.02 to 0.19	-0.04 log10 pg/mL Interval -0.11 to 0.05
Change in IL-6 Change from week 14/16 to week 28	-0.08 log10 pg/mL Interval -0.27 to 0.03	0.01 log10 pg/mL Interval -0.07 to 0.13
Change in IL-6 Change from baseline to week 28	0.02 log10 pg/mL Interval -0.14 to 0.17	-0.01 log10 pg/mL Interval -0.14 to 0.16

SECONDARY outcome

Timeframe: baseline, week 14/16, week 28

Population: The analysis is complete case as-treated, and is limited to participants who: * have data for both baseline and week 14/16 * (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses) * did not use prohibited medications * did not experience virologic failure from baseline to week 16

hsCRP (high-sensitivity C-reactive protein) is a marker of inflammation. Change in log10 transformed hsCRP from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).

Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.

Outcome measures

Measure	Isotretinoin Arm n=39 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment
Change in hsCRP Change from baseline to week 14/16	0.20 log10 ng/mL Interval -0.07 to 0.32	-0.08 log10 ng/mL Interval -0.21 to 0.19
Change in hsCRP Change from week 14/16 to week 28	-0.24 log10 ng/mL Interval -0.52 to -0.06	0.11 log10 ng/mL Interval -0.06 to 0.31
Change in hsCRP Change from baseline to week 28	-0.09 log10 ng/mL Interval -0.39 to 0.18	-0.05 log10 ng/mL Interval -0.15 to 0.29

SECONDARY outcome

Timeframe: baseline, week 14/16, week 28

Population: The analysis is complete case as-treated, and is limited to participants who: * have data for both baseline and week 14/16 * (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses) * did not use prohibited medications * did not experience virologic failure from baseline to week 16

sTNF-r1 (soluble tumour necrosis alpha receptor 1) is a marker of inflammation. Change in log10 transformed sTNF-r1 from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).

Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.

Outcome measures

Measure	Isotretinoin Arm n=39 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment
Change in sTNF-r1 Change from baseline to week 14/16	0.00 log10 pg/mL Interval -0.02 to 0.03	0.01 log10 pg/mL Interval -0.03 to 0.05
Change in sTNF-r1 Change from week 14/16 to week 28	0.00 log10 pg/mL Interval -0.04 to 0.02	0.00 log10 pg/mL Interval -0.03 to 0.04
Change in sTNF-r1 Change from baseline to week 28	0.00 log10 pg/mL Interval -0.04 to 0.03	0.02 log10 pg/mL Interval -0.03 to 0.04

SECONDARY outcome

Timeframe: baseline, week 14/16, week 28

Population: The analysis is complete case as-treated, and is limited to participants who: * have data for both baseline and week 14/16 * (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses) * did not use prohibited medications * did not experience virologic failure from baseline to week 16

sTNF-r2 (soluble tumour necrosis alpha receptor 2) is a marker of inflammation. Change in log10 transformed sTNF-r2 from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).

Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.

Outcome measures

Measure	Isotretinoin Arm n=39 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment
Change in sTNF-r2 Change from baseline to week 14/16	0.03 log10 pg/mL Interval -0.02 to 0.07	0.01 log10 pg/mL Interval -0.02 to 0.05
Change in sTNF-r2 Change from week 14/16 to week 28	-0.02 log10 pg/mL Interval -0.08 to 0.03	0.00 log10 pg/mL Interval -0.04 to 0.04
Change in sTNF-r2 Change from baseline to week 28	0.00 log10 pg/mL Interval -0.03 to 0.04	0.02 log10 pg/mL Interval -0.02 to 0.06

SECONDARY outcome

Timeframe: baseline, week 14/16, week 28

Population: The analysis is complete case as-treated, and is limited to participants who: * have data for both baseline and week 14/16 * (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses) * did not use prohibited medications * did not experience virologic failure from baseline to week 16

D-dimer (or D dimer) is a marker of coagulation activation. Change in log10 transformed D-dimer from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).

Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.

Outcome measures

Measure	Isotretinoin Arm n=39 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment
Change in D-dimer Change from baseline to week 14/16	0.10 log10 ng/mL Interval 0.01 to 0.2	0.02 log10 ng/mL Interval -0.05 to 0.15
Change in D-dimer Change from week 14/16 to week 28	-0.04 log10 ng/mL Interval -0.22 to 0.03	0.00 log10 ng/mL Interval -0.04 to 0.07
Change in D-dimer Change from baseline to week 28	0.01 log10 ng/mL Interval -0.07 to 0.14	0.09 log10 ng/mL Interval -0.05 to 0.14

SECONDARY outcome

Timeframe: baseline, week 14/16, week 28

Population: The analysis is complete case as-treated, and is limited to participants who: * have data for both baseline and week 14/16 * (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses) * did not use prohibited medications * did not experience virologic failure from baseline to week 16

TF (Tissue Factor) is a marker of Coagulation. Change in log10 transformed TF from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).

Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.

Outcome measures

Measure	Isotretinoin Arm n=39 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment
Change in TF Change from baseline to week 14/16	-0.01 log10 pg/mL Interval -0.02 to 0.03	0.01 log10 pg/mL Interval -0.02 to 0.05
Change in TF Change from week 14/16 to week 28	0.00 log10 pg/mL Interval -0.07 to 0.03	0.01 log10 pg/mL Interval 0.0 to 0.04
Change in TF Change from baseline to week 28	-0.02 log10 pg/mL Interval -0.06 to 0.03	0.03 log10 pg/mL Interval 0.01 to 0.07

SECONDARY outcome

Timeframe: baseline, week 14/16, week 28

Population: The analysis is complete case as-treated, and is limited to participants who: * have data for both baseline and week 14/16 * (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses) * did not use prohibited medications * did not experience virologic failure from baseline to week 16

sCD163 (soluble CD 163) is a marker of macrophage activation Change in log10 transformed sCD163 from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).

Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.

Outcome measures

Measure	Isotretinoin Arm n=39 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment
Change in sCD163 Change from baseline to week 14/16	0.15 log10 ng/mL Interval 0.04 to 0.22	-0.01 log10 ng/mL Interval -0.04 to 0.12
Change in sCD163 Change from week 14/16 to week 28	-0.14 log10 ng/mL Interval -0.19 to -0.05	-0.01 log10 ng/mL Interval -0.08 to 0.05
Change in sCD163 Change from baseline to week 28	-0.02 log10 ng/mL Interval -0.1 to 0.15	0.04 log10 ng/mL Interval -0.08 to 0.21

SECONDARY outcome

Timeframe: baseline, week 14/16, week 28

Population: The analysis is complete case as-treated, and is limited to participants who: * have data for both baseline and week 14/16 * (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses) * did not use prohibited medications * did not experience virologic failure from baseline to week 16

Change in peripheral total CD4 cell count from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).

Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.

Outcome measures

Measure	Isotretinoin Arm n=39 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment
Change in CD4+ T-cell Count Change from baseline to week 14/16	17 cells/mm^3 Interval -35.0 to 43.0	-39 cells/mm^3 Interval -124.0 to 19.0
Change in CD4+ T-cell Count Change from baseline to week 28	27 cells/mm^3 Interval -18.0 to 89.0	-14 cells/mm^3 Interval -76.0 to 30.0
Change in CD4+ T-cell Count Change from week 14/16 to week 28	31 cells/mm^3 Interval -10.0 to 75.0	21 cells/mm^3 Interval -31.0 to 81.0

SECONDARY outcome

Timeframe: baseline, week 14/16, week 28

Population: The analysis is complete case as-treated, and is limited to participants who: * have data for both baseline and week 14/16 * (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses) * did not use prohibited medications * did not experience virologic failure from baseline to week 16 * have cell-associated HIV-1 RNA data

Cell-associated HIV-1 RNA in blood from baseline to week 14/16(week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).

Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.

For cell-associated HIV-1 RNA results below the assay limit, the lowest value of the sample was imputed to these results (1.32 log10 copies/10^6 CD4 cells).

Since there are only a few results below the assay limit, it is still reasonable to summarize the absolute changes for cell-associated HIV-1 RNA, where changes were calculated based on the imputed values (described above) for below assay limit results.

Outcome measures

Measure	Isotretinoin Arm n=37 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment
Change in Cell-associated HIV-1 RNA Change from baseline to week 14/16	-0.09 log10 copies/million CD4 cells Interval -0.32 to 0.24	-0.02 log10 copies/million CD4 cells Interval -0.22 to 0.25
Change in Cell-associated HIV-1 RNA Change from week 14/16 to week 28	-0.03 log10 copies/million CD4 cells Interval -0.28 to 0.22	-0.20 log10 copies/million CD4 cells Interval -0.51 to 0.04
Change in Cell-associated HIV-1 RNA Change from baseline to week 28	-0.08 log10 copies/million CD4 cells Interval -0.28 to 0.13	-0.18 log10 copies/million CD4 cells Interval -0.46 to 0.12

SECONDARY outcome

Timeframe: baseline, week 14/16, week 28

Population: The analysis is complete case as-treated, and is limited to participants who: * have data for both baseline and week 14/16 * (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses) * did not use prohibited medications * did not experience virologic failure from baseline to week 16 * have cell-associated HIV-1 DNA data

Cell-associated HIV-1 DNA in blood at baseline, week 14/16, and week 28. Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.

For cell-associated HIV-1 DNA results below the assay limit, the lowest value of the sample was imputed to these results and considered lowest ranks (1.62 log10 copies/10^6 CD4 cells).

It was originally planned to summarize the absolute changes for cell-associated HIV-1 DNA. However, since there are many results below limit of detection, analyzing the absolute changes would be inappropriate in this case.

Instead, the baseline, week 14/16, and week 28 levels were summarized.

Outcome measures

Measure	Isotretinoin Arm n=39 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment
Cell-associated HIV-1 DNA baseline	2.55 log10 copies/million CD4 cells Interval 2.03 to 2.99	2.72 log10 copies/million CD4 cells Interval 2.39 to 2.94
Cell-associated HIV-1 DNA week 14/16	2.52 log10 copies/million CD4 cells Interval 2.25 to 2.79	2.66 log10 copies/million CD4 cells Interval 2.23 to 2.88
Cell-associated HIV-1 DNA week 28	2.64 log10 copies/million CD4 cells Interval 1.78 to 2.95	2.55 log10 copies/million CD4 cells Interval 2.21 to 2.82

SECONDARY outcome

Timeframe: baseline, week 14/16, week 28

Population: The analysis is complete case as-treated, and is limited to participants who: * have data for both baseline and week 14/16 * (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses) * did not use prohibited medications * did not experience virologic failure from baseline to week 16

Treg (T Regulatory) Cells are a subpopulation of T cells which modulate the immune system.

The outcome measure is the change in percent FoxP3+/CD25hi+/CD39+/CD127-(CD4+) from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).

Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.

Outcome measures

Measure	Isotretinoin Arm n=39 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment
Change in Treg Frequency (%FoxP3+/CD25hi+/CD39+/CD127-(CD4+)) Change from baseline to week 14/16	0.00 percentage of CD4 cells Interval -0.46 to 0.2	-0.03 percentage of CD4 cells Interval -0.29 to 0.25
Change in Treg Frequency (%FoxP3+/CD25hi+/CD39+/CD127-(CD4+)) Change from week 14/16 to week 28	0.00 percentage of CD4 cells Interval -0.28 to 0.26	0.02 percentage of CD4 cells Interval -0.11 to 0.21
Change in Treg Frequency (%FoxP3+/CD25hi+/CD39+/CD127-(CD4+)) Change from baseline to week 28	-0.03 percentage of CD4 cells Interval -0.36 to 0.09	0.11 percentage of CD4 cells Interval -0.26 to 0.26

SECONDARY outcome

Timeframe: baseline, week 14/16, week 28

Population: The analysis is complete case as-treated, and is limited to participants who: * have data for both baseline and week 14/16 * (for the Isotretinoin arm) completed treatment (allowing ≤8 missed doses) * did not use prohibited medications * did not experience virologic failure from baseline to week 16

Th17 (T-helper 17) cells are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17).

The outcome is the change in percent IFNg-/IL17+(CD161+/CCR6+) from baseline to week 14/16 (week 14/16 - baseline), from week 14/16 to week 28 (week 28 - week 14/16), and from baseline to week 28 (week 28 - baseline).

Levels measured at pre-entry and entry were averaged for baseline, levels measured at week 14 and week 16 were averaged for week 14/16.

Outcome measures

Measure	Isotretinoin Arm n=39 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment
Change in Th17 Frequency (%IFNg-/IL17+(CD161+/CCR6+)) Change from baseline to week 28	-0.05 percentage of CD161+/CCR6+ cells Interval -0.5 to 0.14	-0.01 percentage of CD161+/CCR6+ cells Interval -0.85 to 0.52
Change in Th17 Frequency (%IFNg-/IL17+(CD161+/CCR6+)) Change from baseline to week 14/16	-0.04 percentage of CD161+/CCR6+ cells Interval -0.42 to 0.14	0.01 percentage of CD161+/CCR6+ cells Interval -0.31 to 0.54
Change in Th17 Frequency (%IFNg-/IL17+(CD161+/CCR6+)) Change from week 14/16 to week 28	0.02 percentage of CD161+/CCR6+ cells Interval -0.33 to 0.28	-0.07 percentage of CD161+/CCR6+ cells Interval -0.41 to 0.18

SECONDARY outcome

Timeframe: weeks 0, 20, 28

Population: Included only Isotretinoin arm participants who were on Isotretinoin for 8 weeks of more.

Isotretinoin Arm (Arm A) only. Endogenous retinoid metabolites are defined as the average concentrations of Retinol, and Total Retinyl Ester from weeks 0, 20, and 28.

Outcome measures

Measure	Isotretinoin Arm n=39 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm No Isotretinoin treatment
Pharmacokinetics - Endogenous Levels of Retinoid Metabolites for Isotretinoin Arm Retinol	2.4 nmol/mL Interval 1.8 to 2.7	—
Pharmacokinetics - Endogenous Levels of Retinoid Metabolites for Isotretinoin Arm Total Retinyl Ester	0.5 nmol/mL Interval 0.4 to 0.6	—

SECONDARY outcome

Timeframe: weeks 8, 12, 16

Population: Included only Isotretinoin arm participants who were on Isotretinoin for 8 weeks of more and have steady state troughs available.

Isotretinoin arm (Arm A) only, steady-state trough concentrations of Isotretinoin is defined as the average of 'eligible' concentrations at weeks 8, 12, and 16, where 'eligible' means the time from the previous dose to the blood draw of the sample must have been in the 14-to-30 hour range, and the participant must have taken at least 3 doses in the prior 4 days.

Outcome measures

Measure	Isotretinoin Arm n=30 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm No Isotretinoin treatment
Pharmacokinetics - Steady-state Trough Concentrations of Isotretinoin for Isotretinoin Arm All	205 pmol/mL Interval 152.0 to 263.0	—
Pharmacokinetics - Steady-state Trough Concentrations of Isotretinoin for Isotretinoin Arm With EFV	228 pmol/mL Interval 120.0 to 265.0	—
Pharmacokinetics - Steady-state Trough Concentrations of Isotretinoin for Isotretinoin Arm No EFV	202 pmol/mL Interval 152.0 to 241.0	—

SECONDARY outcome

Timeframe: weeks 0, 8, 12, 16, 20

Population: Included only Isotretinoin arm participants who were on TDF and on Isotretinoin for 8 weeks of more, and with available TDF trough.

Isotretinoin arm (Arm A) only, trough concentrations of TDF (Tenofovir) is defined as the average of 'eligible' concentrations, where 'eligible' means the time from the previous dose to the blood draw of the sample must have been in the 20-to-28 hour range, and the participant must have taken at least 3 doses in the prior 4 days.

TDF trough during Isotretinoin administration is the average of 'eligible' concentrations from weeks 8, 12, and 16; TDF trough without Isotretinoin administration is the average of 'eligible' concentrations from weeks 0 and 20.

(Week 28 data is not available.)

Outcome measures

Measure	Isotretinoin Arm n=15 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm No Isotretinoin treatment
Pharmacokinetics - Trough Concentrations of TDF for Isotretinoin Arm With Isotretinoin	82 ng/mL Interval 52.0 to 107.0	—
Pharmacokinetics - Trough Concentrations of TDF for Isotretinoin Arm Without Isotretinoin	63 ng/mL Interval 46.0 to 87.0	—

SECONDARY outcome

Timeframe: weeks 0, 8, 12, 16, 20

Population: Included only Isotretinoin arm participants who were on EFV and on Isotretinoin for 8 weeks of more, and with available EFV 12-hour levels.

Isotretinoin arm (Arm A) only, 12-hour levels of EFV (Efavirenz) is defined as the average of 'eligible' concentrations, where 'eligible' means the time from the previous dose to the blood draw of the sample must have been in the 9-to-15 hour range, and the participant must have taken at least 3 doses in the prior 4 days.

EFV trough during Isotretinoin administration is the average of 'eligible' concentrations from weeks 8, 12, and 16; EFV trough without Isotretinoin administration is the average of 'eligible' concentrations from weeks 0 and 20.

(Week 28 data is not available.)

Outcome measures

Measure	Isotretinoin Arm n=11 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm No Isotretinoin treatment
Pharmacokinetics - 12-hour Levels of EFV for Isotretinoin Arm With Isotretinoin	2607 ng/mL Interval 1648.0 to 4343.0	—
Pharmacokinetics - 12-hour Levels of EFV for Isotretinoin Arm Without Isotretinoin	2665 ng/mL Interval 1849.0 to 3421.0	—

SECONDARY outcome

Timeframe: from study entry to end of study (week 28)

Population: all enrolled participants

Targeted events for A5325 include: events that meet the International Conference on Harmonization (ICH) definitions for a serious adverse event, post-entry signs/symptoms and laboratory abnormalities of Grade ≥3 or that lead to a change in treatment regardless of grade, and any diagnoses.

Outcome measures

Measure	Isotretinoin Arm n=50 Participants Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment Arm n=26 Participants No Isotretinoin treatment
Primary Targeted Adverse Events	18 Participants	6 Participants

Adverse Events

Isotretinoin

Serious events: 2 serious events

Other events: 41 other events

Deaths: 0 deaths

No Study Treatment

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	Isotretinoin n=50 participants at risk Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment n=26 participants at risk No Isotretinoin treatment
Infections and infestations Meningitis viral	2.0% 1/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	0.00% 0/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Infections and infestations Pyelonephritis	2.0% 1/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	0.00% 0/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.

Other adverse events

Measure	Isotretinoin n=50 participants at risk Participants received Isotretinoin at approximately 0.5 mg/kg orally once daily for 4 weeks, then increased to approximately 1.0 mg/kg orally once daily for 12 weeks.	No Study Treatment n=26 participants at risk No Isotretinoin treatment
Infections and infestations Upper respiratory tract infection	0.00% 0/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	7.7% 2/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Alanine aminotransferase increased	0.00% 0/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	15.4% 4/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Aspartate aminotransferase increased	0.00% 0/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	11.5% 3/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Blood alkaline phosphatase increased	6.0% 3/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	7.7% 2/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Blood bicarbonate decreased	6.0% 3/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	3.8% 1/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Blood bilirubin increased	14.0% 7/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	7.7% 2/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Blood cholesterol increased	40.0% 20/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	42.3% 11/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Blood creatinine increased	6.0% 3/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	7.7% 2/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Blood glucose decreased	6.0% 3/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	3.8% 1/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Blood glucose increased	20.0% 10/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	19.2% 5/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Blood potassium decreased	6.0% 3/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	7.7% 2/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Blood sodium decreased	6.0% 3/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	3.8% 1/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Lipase abnormal	6.0% 3/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	7.7% 2/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Low density lipoprotein increased	36.0% 18/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	30.8% 8/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Neutrophil count decreased	4.0% 2/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	7.7% 2/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Investigations Platelet count decreased	4.0% 2/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	7.7% 2/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Nervous system disorders Headache	6.0% 3/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	0.00% 0/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	7.7% 2/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.
Skin and subcutaneous tissue disorders Dry skin	6.0% 3/50 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.	0.00% 0/26 • Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks Expedited adverse event (EAE) reporting followed the Division of AIDS (DAIDS) EAE Manual under the SAE Reporting Category and including fetal losses. Events were graded (1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death) according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, Clarification Aug 2009.

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 In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER