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Trial record 2 of 163 for:    ISOTRETINOIN

Effect of Isotretinoin on Immune Activation Among HIV-1 Infected Subjects With Incomplete CD4+ T Cell Recovery

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ClinicalTrials.gov Identifier: NCT01969058
Recruitment Status : Completed
First Posted : October 25, 2013
Results First Posted : September 5, 2017
Last Update Posted : April 3, 2019
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV-1 Infection
Intervention Drug: Isotretinoin
Enrollment 76
Recruitment Details 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
Pre-assignment Details 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.
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description 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 Isotretinoin treatment
Period Title: Overall Study
Started 50 26
Completed 47 26
Not Completed 3 0
Reason Not Completed
Withdrawal by Subject             2             0
Adverse Event             1             0
Arm/Group Title Isotretinoin Arm No Study Treatment Arm Total
Hide Arm/Group Description 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 Isotretinoin treatment Total of all reporting groups
Overall Number of Baseline Participants 50 26 76
Hide Baseline Analysis Population Description
All enrolled participants
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 50 participants 26 participants 76 participants
49
(38 to 55)
51
(38 to 53)
49
(38 to 55)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
18-39 years Number Analyzed 50 participants 26 participants 76 participants
14
  28.0%
7
  26.9%
21
  27.6%
40-59 years Number Analyzed 50 participants 26 participants 76 participants
31
  62.0%
16
  61.5%
47
  61.8%
>=60 years Number Analyzed 50 participants 26 participants 76 participants
5
  10.0%
3
  11.5%
8
  10.5%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 26 participants 76 participants
Female
4
   8.0%
1
   3.8%
5
   6.6%
Male
46
  92.0%
25
  96.2%
71
  93.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Non-Hispanic White Number Analyzed 50 participants 26 participants 76 participants
18
  36.0%
12
  46.2%
30
  39.5%
Non-Hispanic Black Number Analyzed 50 participants 26 participants 76 participants
21
  42.0%
9
  34.6%
30
  39.5%
Hispanic (Regardless of Race) Number Analyzed 50 participants 26 participants 76 participants
11
  22.0%
5
  19.2%
16
  21.1%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Puerto Rico Number Analyzed 50 participants 26 participants 76 participants
1
   2.0%
0
   0.0%
1
   1.3%
United States Number Analyzed 50 participants 26 participants 76 participants
49
  98.0%
26
 100.0%
75
  98.7%
HIV-1 RNA  
Measure Type: Count of Participants
Unit of measure:  Participants
>= Assay lower limit (40 copies/mL) Number Analyzed 50 participants 26 participants 76 participants
0
   0.0%
1
   3.8%
1
   1.3%
< Assay lower limit (40 copies/mL) Number Analyzed 50 participants 26 participants 76 participants
50
 100.0%
25
  96.2%
75
  98.7%
CD4+ Cell Count  
Median (Inter-Quartile Range)
Unit of measure:  Cells/mm^3
Number Analyzed 50 participants 26 participants 76 participants
549
(299 to 754)
556
(342 to 781)
552
(310 to 768)
BMI  
Median (Inter-Quartile Range)
Unit of measure:  Kg/m^2
Number Analyzed 50 participants 26 participants 76 participants
27.1
(23.1 to 29.3)
26.9
(22.6 to 27.9)
27.1
(22.9 to 29.2)
CD8+ T-cell Activation Percent   [1] [2] 
Median (Inter-Quartile Range)
Unit of measure:  Percentage of cells
Number Analyzed 39 participants 26 participants 65 participants
13.67
(10.35 to 19.49)
13.40
(8.43 to 18.56)
13.66
(9.83 to 19.29)
[1]
Measure Description:

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

Baseline is defined as the average of pre-entry and entry values

[2]
Measure Analysis Population Description: 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.
1.Primary Outcome
Title Change in CD8+ T-cell Activation From Baseline to Week 14/16
Hide Description

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).

Time Frame baseline, week 14/16
Hide Outcome Measure Data
Hide Analysis Population Description

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
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description:
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 Isotretinoin treatment
Overall Number of Participants Analyzed 39 26
Median (Inter-Quartile Range)
Unit of Measure: percentage of cells
3.24
(0.77 to 7.75)
0.52
(-0.41 to 2.86)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Isotretinoin Arm, No Study Treatment Arm
Comments Null hypothesis: There is no difference between the two arms in the change in T-cell activation from baseline to week 14/16.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments Not adjusted for multiple comparisons.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Secondary Outcome
Title Change in CD8+ T-cell Activation
Hide Description

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.

Time Frame baseline, week 14/16, week 28
Hide Outcome Measure Data
Hide Analysis Population Description

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
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description:
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 Isotretinoin treatment
Overall Number of Participants Analyzed 39 26
Median (Inter-Quartile Range)
Unit of Measure: percentage of cells
Change from week 14/16 to week 28
-3.58
(-8.45 to 0.35)
-0.91
(-3.40 to 1.49)
Change from baseline to week 28
-0.69
(-2.61 to 4.00)
0.03
(-2.34 to 3.32)
3.Secondary Outcome
Title Change in sCD14
Hide Description

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.

Time Frame baseline, week 14/16, week 28
Hide Outcome Measure Data
Hide Analysis Population Description

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
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description:
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 Isotretinoin treatment
Overall Number of Participants Analyzed 39 26
Median (Inter-Quartile Range)
Unit of Measure: log10 pg/mL
Change from baseline to week 14/16
0.02
(-0.03 to 0.10)
-0.02
(-0.06 to 0.05)
Change from week 14/16 to week 28
-0.06
(-0.13 to 0.02)
0.02
(-0.04 to 0.06)
Change from baseline to week 28
-0.02
(-0.07 to 0.05)
0.00
(-0.06 to 0.05)
4.Secondary Outcome
Title Change in I-FABP
Hide Description

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.

Time Frame baseline, week 14/16, week 28
Hide Outcome Measure Data
Hide Analysis Population Description

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
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description:
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 Isotretinoin treatment
Overall Number of Participants Analyzed 39 26
Median (Inter-Quartile Range)
Unit of Measure: log10 pg/mL
Change from baseline to week 14/16
-0.03
(-0.14 to 0.10)
0.04
(-0.05 to 0.17)
Change from week 14/16 to week 28
0.09
(-0.01 to 0.16)
-0.05
(-0.15 to 0.05)
Change from baseline to week 28
0.07
(-0.05 to 0.20)
-0.07
(-0.19 to 0.11)
5.Secondary Outcome
Title Change in IL-6
Hide Description

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.

Time Frame baseline, week 14/16, week 28
Hide Outcome Measure Data
Hide Analysis Population Description

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
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description:
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 Isotretinoin treatment
Overall Number of Participants Analyzed 39 26
Median (Inter-Quartile Range)
Unit of Measure: log10 pg/mL
Change from baseline to week 14/16
0.10
(-0.02 to 0.19)
-0.04
(-0.11 to 0.05)
Change from week 14/16 to week 28
-0.08
(-0.27 to 0.03)
0.01
(-0.07 to 0.13)
Change from baseline to week 28
0.02
(-0.14 to 0.17)
-0.01
(-0.14 to 0.16)
6.Secondary Outcome
Title Change in hsCRP
Hide Description

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.

Time Frame baseline, week 14/16, week 28
Hide Outcome Measure Data
Hide Analysis Population Description

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
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description:
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 Isotretinoin treatment
Overall Number of Participants Analyzed 39 26
Median (Inter-Quartile Range)
Unit of Measure: log10 ng/mL
Change from baseline to week 14/16
0.20
(-0.07 to 0.32)
-0.08
(-0.21 to 0.19)
Change from week 14/16 to week 28
-0.24
(-0.52 to -0.06)
0.11
(-0.06 to 0.31)
Change from baseline to week 28
-0.09
(-0.39 to 0.18)
-0.05
(-0.15 to 0.29)
7.Secondary Outcome
Title Change in sTNF-r1
Hide Description

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.

Time Frame baseline, week 14/16, week 28
Hide Outcome Measure Data
Hide Analysis Population Description

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
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description:
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 Isotretinoin treatment
Overall Number of Participants Analyzed 39 26
Median (Inter-Quartile Range)
Unit of Measure: log10 pg/mL
Change from baseline to week 14/16
0.00
(-0.02 to 0.03)
0.01
(-0.03 to 0.05)
Change from week 14/16 to week 28
0.00
(-0.04 to 0.02)
0.00
(-0.03 to 0.04)
Change from baseline to week 28
0.00
(-0.04 to 0.03)
0.02
(-0.03 to 0.04)
8.Secondary Outcome
Title Change in sTNF-r2
Hide Description

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.

Time Frame baseline, week 14/16, week 28
Hide Outcome Measure Data
Hide Analysis Population Description

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
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description:
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 Isotretinoin treatment
Overall Number of Participants Analyzed 39 26
Median (Inter-Quartile Range)
Unit of Measure: log10 pg/mL
Change from baseline to week 14/16
0.03
(-0.02 to 0.07)
0.01
(-0.02 to 0.05)
Change from week 14/16 to week 28
-0.02
(-0.08 to 0.03)
0.00
(-0.04 to 0.04)
Change from baseline to week 28
0.00
(-0.03 to 0.04)
0.02
(-0.02 to 0.06)
9.Secondary Outcome
Title Change in D-dimer
Hide Description

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.

Time Frame baseline, week 14/16, week 28
Hide Outcome Measure Data
Hide Analysis Population Description

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
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description:
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 Isotretinoin treatment
Overall Number of Participants Analyzed 39 26
Median (Inter-Quartile Range)
Unit of Measure: log10 ng/mL
Change from baseline to week 14/16
0.10
(0.01 to 0.20)
0.02
(-0.05 to 0.15)
Change from week 14/16 to week 28
-0.04
(-0.22 to 0.03)
0.00
(-0.04 to 0.07)
Change from baseline to week 28
0.01
(-0.07 to 0.14)
0.09
(-0.05 to 0.14)
10.Secondary Outcome
Title Change in TF
Hide Description

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.

Time Frame baseline, week 14/16, week 28
Hide Outcome Measure Data
Hide Analysis Population Description

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
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description:
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 Isotretinoin treatment
Overall Number of Participants Analyzed 39 26
Median (Inter-Quartile Range)
Unit of Measure: log10 pg/mL
Change from baseline to week 14/16
-0.01
(-0.02 to 0.03)
0.01
(-0.02 to 0.05)
Change from week 14/16 to week 28
0.00
(-0.07 to 0.03)
0.01
(0.00 to 0.04)
Change from baseline to week 28
-0.02
(-0.06 to 0.03)
0.03
(0.01 to 0.07)
11.Secondary Outcome
Title Change in sCD163
Hide Description

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.

Time Frame baseline, week 14/16, week 28
Hide Outcome Measure Data
Hide Analysis Population Description

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
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description:
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 Isotretinoin treatment
Overall Number of Participants Analyzed 39 26
Median (Inter-Quartile Range)
Unit of Measure: log10 ng/mL
Change from baseline to week 14/16
0.15
(0.04 to 0.22)
-0.01
(-0.04 to 0.12)
Change from week 14/16 to week 28
-0.14
(-0.19 to -0.05)
-0.01
(-0.08 to 0.05)
Change from baseline to week 28
-0.02
(-0.10 to 0.15)
0.04
(-0.08 to 0.21)
12.Secondary Outcome
Title Change in CD4+ T-cell Count
Hide Description

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.

Time Frame baseline, week 14/16, week 28
Hide Outcome Measure Data
Hide Analysis Population Description

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
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description:
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 Isotretinoin treatment
Overall Number of Participants Analyzed 39 26
Median (Inter-Quartile Range)
Unit of Measure: cells/mm^3
Change from baseline to week 14/16 Number Analyzed 38 participants 26 participants
17
(-35 to 43)
-39
(-124 to 19)
Change from week 14/16 to week 28 Number Analyzed 38 participants 25 participants
31
(-10 to 75)
21
(-31 to 81)
Change from baseline to week 28 Number Analyzed 39 participants 25 participants
27
(-18 to 89)
-14
(-76 to 30)
13.Secondary Outcome
Title Change in Cell-associated HIV-1 RNA
Hide Description

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.

Time Frame baseline, week 14/16, week 28
Hide Outcome Measure Data
Hide Analysis Population Description

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
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description:
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 Isotretinoin treatment
Overall Number of Participants Analyzed 37 26
Median (Inter-Quartile Range)
Unit of Measure: log10 copies/million CD4 cells
Change from baseline to week 14/16 Number Analyzed 35 participants 26 participants
-0.09
(-0.32 to 0.24)
-0.02
(-0.22 to 0.25)
Change from week 14/16 to week 28 Number Analyzed 33 participants 24 participants
-0.03
(-0.28 to 0.22)
-0.20
(-0.51 to 0.04)
Change from baseline to week 28 Number Analyzed 37 participants 24 participants
-0.08
(-0.28 to 0.13)
-0.18
(-0.46 to 0.12)
14.Secondary Outcome
Title Cell-associated HIV-1 DNA
Hide Description

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.

Time Frame baseline, week 14/16, week 28
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Hide Analysis Population Description

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
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description:
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 Isotretinoin treatment
Overall Number of Participants Analyzed 39 26
Median (Inter-Quartile Range)
Unit of Measure: log10 copies/million CD4 cells
baseline Number Analyzed 39 participants 26 participants
2.55
(2.03 to 2.99)
2.72
(2.39 to 2.94)
week 14/16 Number Analyzed 37 participants 26 participants
2.52
(2.25 to 2.79)
2.66
(2.23 to 2.88)
week 28 Number Analyzed 38 participants 25 participants
2.64
(1.78 to 2.95)
2.55
(2.21 to 2.82)
15.Secondary Outcome
Title Change in Treg Frequency (%FoxP3+/CD25hi+/CD39+/CD127-(CD4+))
Hide Description

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.

Time Frame baseline, week 14/16, week 28
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Hide Analysis Population Description

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
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description:
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 Isotretinoin treatment
Overall Number of Participants Analyzed 39 26
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD4 cells
Change from baseline to week 14/16 Number Analyzed 39 participants 26 participants
0.00
(-0.46 to 0.20)
-0.03
(-0.29 to 0.25)
Change from week 14/16 to week 28 Number Analyzed 38 participants 26 participants
0.00
(-0.28 to 0.26)
0.02
(-0.11 to 0.21)
Change from baseline to week 28 Number Analyzed 38 participants 26 participants
-0.03
(-0.36 to 0.09)
0.11
(-0.26 to 0.26)
16.Secondary Outcome
Title Change in Th17 Frequency (%IFNg-/IL17+(CD161+/CCR6+))
Hide Description

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.

Time Frame baseline, week 14/16, week 28
Hide Outcome Measure Data
Hide Analysis Population Description

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
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description:
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 Isotretinoin treatment
Overall Number of Participants Analyzed 39 26
Median (Inter-Quartile Range)
Unit of Measure: percentage of CD161+/CCR6+ cells
Change from baseline to week 14/16 Number Analyzed 39 participants 26 participants
-0.04
(-0.42 to 0.14)
0.01
(-0.31 to 0.54)
Change from week 14/16 to week 28 Number Analyzed 38 participants 26 participants
0.02
(-0.33 to 0.28)
-0.07
(-0.41 to 0.18)
Change from baseline to week 28 Number Analyzed 38 participants 26 participants
-0.05
(-0.50 to 0.14)
-0.01
(-0.85 to 0.52)
17.Secondary Outcome
Title Pharmacokinetics – Endogenous Levels of Retinoid Metabolites for Isotretinoin Arm
Hide Description 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.
Time Frame weeks 0, 20, 28
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Hide Analysis Population Description
Included only Isotretinoin arm participants who were on Isotretinoin for 8 weeks of more.
Arm/Group Title Isotretinoin Arm
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 39
Median (Inter-Quartile Range)
Unit of Measure: nmol/mL
Retinol
2.4
(1.8 to 2.7)
Total Retinyl Ester
0.5
(0.4 to 0.6)
18.Secondary Outcome
Title Pharmacokinetics – Steady-state Trough Concentrations of Isotretinoin for Isotretinoin Arm
Hide Description 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.
Time Frame weeks 8, 12, 16
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Hide Analysis Population Description
Included only Isotretinoin arm participants who were on Isotretinoin for 8 weeks of more and have steady state troughs available.
Arm/Group Title Isotretinoin Arm
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 30
Median (Inter-Quartile Range)
Unit of Measure: pmol/mL
All Number Analyzed 30 participants
205
(152 to 263)
With EFV Number Analyzed 7 participants
228
(120 to 265)
No EFV Number Analyzed 23 participants
202
(152 to 241)
19.Secondary Outcome
Title Pharmacokinetics – Trough Concentrations of TDF for Isotretinoin Arm
Hide Description

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.)

Time Frame weeks 0, 8, 12, 16, 20
Hide Outcome Measure Data
Hide Analysis Population Description
Included only Isotretinoin arm participants who were on TDF and on Isotretinoin for 8 weeks of more, and with available TDF trough.
Arm/Group Title Isotretinoin Arm
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 15
Median (Inter-Quartile Range)
Unit of Measure: ng/mL
With Isotretinoin
82
(52 to 107)
Without Isotretinoin
63
(46 to 87)
20.Secondary Outcome
Title Pharmacokinetics – 12-hour Levels of EFV for Isotretinoin Arm
Hide Description

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.)

Time Frame weeks 0, 8, 12, 16, 20
Hide Outcome Measure Data
Hide Analysis Population Description
Included only Isotretinoin arm participants who were on EFV and on Isotretinoin for 8 weeks of more, and with available EFV 12-hour levels.
Arm/Group Title Isotretinoin Arm
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 11
Median (Inter-Quartile Range)
Unit of Measure: ng/mL
With Isotretinoin
2607
(1648 to 4343)
Without Isotretinoin
2665
(1849 to 3421)
21.Secondary Outcome
Title Primary Targeted Adverse Events
Hide Description 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.
Time Frame from study entry to end of study (week 28)
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all enrolled participants
Arm/Group Title Isotretinoin Arm No Study Treatment Arm
Hide Arm/Group Description:
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 Isotretinoin treatment
Overall Number of Participants Analyzed 50 26
Measure Type: Count of Participants
Unit of Measure: Participants
18
  36.0%
6
  23.1%
Time Frame Adverse Events (AEs) reported from study enrollment until study completion at 28 weeks
Adverse Event Reporting Description 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.
 
Arm/Group Title Isotretinoin No Study Treatment
Hide Arm/Group Description 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 Isotretinoin treatment
All-Cause Mortality
Isotretinoin No Study Treatment
Affected / at Risk (%) Affected / at Risk (%)
Total   0/50 (0.00%)   0/26 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Isotretinoin No Study Treatment
Affected / at Risk (%) Affected / at Risk (%)
Total   2/50 (4.00%)   0/26 (0.00%) 
Infections and infestations     
Meningitis viral  1  1/50 (2.00%)  0/26 (0.00%) 
Pyelonephritis  1  1/50 (2.00%)  0/26 (0.00%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Isotretinoin No Study Treatment
Affected / at Risk (%) Affected / at Risk (%)
Total   41/50 (82.00%)   18/26 (69.23%) 
Infections and infestations     
Upper respiratory tract infection  1  0/50 (0.00%)  2/26 (7.69%) 
Investigations     
Alanine aminotransferase increased  1  0/50 (0.00%)  4/26 (15.38%) 
Aspartate aminotransferase increased  1  0/50 (0.00%)  3/26 (11.54%) 
Blood alkaline phosphatase increased  1  3/50 (6.00%)  2/26 (7.69%) 
Blood bicarbonate decreased  1  3/50 (6.00%)  1/26 (3.85%) 
Blood bilirubin increased  1  7/50 (14.00%)  2/26 (7.69%) 
Blood cholesterol increased  1  20/50 (40.00%)  11/26 (42.31%) 
Blood creatinine increased  1  3/50 (6.00%)  2/26 (7.69%) 
Blood glucose decreased  1  3/50 (6.00%)  1/26 (3.85%) 
Blood glucose increased  1  10/50 (20.00%)  5/26 (19.23%) 
Blood potassium decreased  1  3/50 (6.00%)  2/26 (7.69%) 
Blood sodium decreased  1  3/50 (6.00%)  1/26 (3.85%) 
Lipase abnormal  1  3/50 (6.00%)  2/26 (7.69%) 
Low density lipoprotein increased  1  18/50 (36.00%)  8/26 (30.77%) 
Neutrophil count decreased  1  2/50 (4.00%)  2/26 (7.69%) 
Platelet count decreased  1  2/50 (4.00%)  2/26 (7.69%) 
Nervous system disorders     
Headache  1  3/50 (6.00%)  0/26 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Nasal congestion  1  0/50 (0.00%)  2/26 (7.69%) 
Skin and subcutaneous tissue disorders     
Dry skin  1  3/50 (6.00%)  0/26 (0.00%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
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Name/Title: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Phone: (301) 628-3313
EMail: ACTGCT.Gov@s-3.com
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Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01969058     History of Changes
Other Study ID Numbers: ACTG A5325
UM1AI068636 ( U.S. NIH Grant/Contract )
First Submitted: August 21, 2013
First Posted: October 25, 2013
Results First Submitted: August 4, 2017
Results First Posted: September 5, 2017
Last Update Posted: April 3, 2019