Effect of Isotretinoin on Immune Activation Among HIV-1 I... | NCT01969058

NCT01969058

ID	Type	Description	Link
UM1AI068636	U.S. NIH Grant/Contract		View source

Status Module

Sponsor/Collaborators Module

Name	Class
National Institute of Allergy and Infectious Diseases (NIAID)	NIH

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Isotretinoin Arm	Active Comparator	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.	Drug: Isotretinoin
No study treatment Arm	No Intervention	No Isotretinoin treatment

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Isotretinoin	Drug	Isotretinoin is a drug that is approved for use in the treatment of severe acne. The aim of this study is to evaluate the role of Isotretinoin on immune activation and inflammation.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in CD8+ T-cell Activation From Baseline to Week 14/16	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).	baseline, week 14/16

Secondary Outcomes

Measure	Description	Time Frame
Change in CD8+ T-cell Activation	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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

- HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.

NOTE: The term "licensed" refers to a US FDA-approved kit, which is required for all IND studies.

CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (eg, indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.

Receiving ART therapy for at least 12 months prior to study entry.
No plans to change the ART regimen in the 6 months after study entry.
HIV-1 RNA below the lower limit of detection using an FDA-approved assay obtained within 30 days prior to study entry by any laboratory that has a CLIA certification or its equivalent (eg, <50 copies/mL on Roche Amplicor HIV-1 Monitor assay, <75 copies/mL on the Versant HIV-1 RNA assay by branched DNA, <40 copies/mL on the Abbott m2000sp/m2000rt real-time PCR test, < 20 copies/mL on the COBAS AmpliPrep/TAQMAN HIV-1 assay).
All measurements of HIV-1 RNA within the 12 months prior to study entry must be below the limit of detection with the following exception:

NOTE A: 1 viral blip (<200 copies/mL) is permitted if it is preceded and followed by viral loads below the limits of detection.

NOTE B: The virologic assay must have a lower limit of detection of ≤ 75 copies/mL.

CD4+ cell count <350 cells/mm3 obtained at screening within 30 days prior to entry at any laboratory that has a CLIA (Clinical Laboratory Improvement Amendments) certification or its equivalent.
The following laboratory values obtained within 30 days prior to entry by any laboratory that has a CLIA certification or its equivalent:
1. Hemoglobin A1c (HgbA1c) levels ≤ 6.5%
2. Hemoglobin ≥ 9.0 g/dL
3. Platelet count ≥ 50,000/mm3
4. Creatinine ≤1.5 mg/dl
5. CrCl ≥ 60 mL/min, calculated by the Cockcroft-Gault method
6. Aspartate aminotransferase (AST) (SGOT) ≤1.5x upper limit of normal (ULN)
7. Alanine aminotransferase (ALT) (SGPT) ≤1.5x ULN
8. Serum lipase ≤1.5x ULN
9. Fasting triglyceride level ≤200 mg/dL
10. Fasting glucose <126mg/dL
Karnofsky performance score >/=70 within 30 days prior to entry.
Men and post-menopausal females aged ≥ 18 years and ≤ 80 years at entry.

Note: Post-menopausal is defined as having either:

Appropriate medical documentation (see note) of prior complete bilateral oophorectomy (i.e., surgical removal of the ovaries, resulting in "surgical menopause" and occurring at the age at which the procedure was performed), OR
Permanent cessation (12 consecutive months or more of amenorrhea) of previously occurring menses as a result of ovarian failure with documentation of hormonal deficiency by a certified healthcare provider (i.e., "spontaneous menopause").

Hormonal deficiency should be properly documented (see note) in the case of suspected spontaneous menopause as follows:

If age >54 years and with the absence of normal menses: Serum FSH (Follicle Stimulating Hormone) level elevated to within the post-menopausal range based on the laboratory reference range where the hormonal assay is performed.
If age ≤ 54 years and with the absence of normal menses: Negative serum or urine HCG with concurrently elevated serum FSH (follicle stimulating hormone) level in the post-menopausal range, depressed estradiol (E2) level in the post-menopausal range, and absent serum progesterone level, based on the laboratory reference ranges where the hormonal assays are performed.

NOTE: "Appropriate documentation", and "properly documented" means written documentation or oral communication from a clinician or clinician's staff documented in source documents of an operative report, discharge summary, or

No active hepatitis B or C infection. NOTE: For subjects who have documentation of prior infection, but no active hepatitis infection, evidence of clearance must be greater than 1 year.
Ability and willingness of subject to provide informed consent.
Willingness to adhere to the iPLEDGE program requirements.
Indication of willingness to participate in the substudy A5330s. NOTE: In the event that 12 or fewer subjects have enrolled into A5330s by the time enrollment in the main study has reached 50% of the accrual target, A5330s enrollment will be required.

Exclusion Criteria:

Pre-existing diagnosis of diabetes.
Currently receiving treatment with fibrate, nicotinic acid, tetracycline, fish oil >1g/d, or methotrexate.
Known active healing fracture or any severe bone disorders. NOTE: does not include healed fractures or history of old fractures.
Receipt of any of the following medications within 30 days prior to entry: systemic steroids (including intra-articular steroids; inhaled or nasal steroid therapy is permitted), interleukins, systemic interferons (including intra-articular steroid injection; local injection of interferon alpha for treatment of human papilloma virus is permitted), or systemic chemotherapy.
Known allergy/sensitivity or any hypersensitivity to vitamin A, retinoids, or any of their derivatives.
Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
Acute or serious illness requiring systemic treatment and/or hospitalization within 60 days prior to entry.
Weight < 40 kg or > 150 kg.
History of major depression or suicide attempt requiring hospitalization, or psychotic episode requiring medication or hospitalization.
History of inflammatory bowel disease such as Crohn's disease, or Ulcerative colitis.

Contacts/Locations Module

Name	Affiliation	Role
Douglas Kwon, MD, PhD	Massachusetts General Hospital	Study Chair
Nina Lin, MD	Harvard Medical School (HMS and HSDM)	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
31788 Alabama CRS		Birmingham	Alabama	35294	United States
601 University of California, Los Angeles CARE Center CRS

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	No Study Treatment Arm

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

Masking Info

No Isotretinoin treatment

All enrolled participants

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	No Study Treatment Arm	No Isotretinoin treatment
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Inter-Quartile Range

years

Title

Denominators

Categories

Title	Measurements
	OG0003.24(0.77 to 7.75) OG0010.52(-0.41 to 2.86)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Null hypothesis: There is no difference between the two arms in the change in T-cell activation from baseline to week 14/16.	Wilcoxon (Mann-Whitney)		0.030	Not adjusted for multiple comparisons.													Superiority

Secondary

Change in CD8+ T-cell Activation

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.

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

Posted

Median

Inter-Quartile Range

percentage of cells

baseline, week 14/16, week 28

ID	Title	Description
OG000	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.
OG001	No Study Treatment Arm	No Isotretinoin treatment

Units	Counts

Secondary

Change in sCD14

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.

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

Posted

Median

Inter-Quartile Range

log10 pg/mL

baseline, week 14/16, week 28

ID	Title	Description
OG000	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.
OG001	No Study Treatment Arm	No Isotretinoin treatment

Units	Counts

Secondary

Change in I-FABP

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.

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

Posted

Median

Inter-Quartile Range

log10 pg/mL

baseline, week 14/16, week 28

ID	Title	Description
OG000	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.
OG001	No Study Treatment Arm	No Isotretinoin treatment

Units	Counts

Secondary

Change in IL-6

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.

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

Posted

Median

Inter-Quartile Range

log10 pg/mL

baseline, week 14/16, week 28

ID	Title	Description
OG000	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.
OG001	No Study Treatment Arm	No Isotretinoin treatment

Units	Counts
Participants

Secondary

Change in hsCRP

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.

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

Posted

Median

Inter-Quartile Range

log10 ng/mL

baseline, week 14/16, week 28

ID	Title	Description
OG000	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.
OG001	No Study Treatment Arm	No Isotretinoin treatment

Units	Counts
Participants

Secondary

Change in sTNF-r1

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.

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

Posted

Median

Inter-Quartile Range

log10 pg/mL

baseline, week 14/16, week 28

ID	Title	Description
OG000	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.
OG001	No Study Treatment Arm	No Isotretinoin treatment

Units	Counts
Participants

Secondary

Change in sTNF-r2

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.

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

Posted

Median

Inter-Quartile Range

log10 pg/mL

baseline, week 14/16, week 28

ID	Title	Description
OG000	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.
OG001	No Study Treatment Arm	No Isotretinoin treatment

Units	Counts
Participants

Secondary

Change in D-dimer

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.

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

Posted

Median

Inter-Quartile Range

log10 ng/mL

baseline, week 14/16, week 28

ID	Title	Description
OG000	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.
OG001	No Study Treatment Arm	No Isotretinoin treatment

Units	Counts
Participants

Secondary

Change in TF

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.

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

Posted

Median

Inter-Quartile Range

log10 pg/mL

baseline, week 14/16, week 28

ID	Title	Description
OG000	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.
OG001	No Study Treatment Arm	No Isotretinoin treatment

Units	Counts
Participants

Secondary

Change in sCD163

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.

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

Posted

Median

Inter-Quartile Range

log10 ng/mL

baseline, week 14/16, week 28

ID	Title	Description
OG000	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.
OG001	No Study Treatment Arm	No Isotretinoin treatment

Units	Counts
Participants

Secondary

Change in CD4+ T-cell Count

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.

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

Posted

Median

Inter-Quartile Range

cells/mm^3

baseline, week 14/16, week 28

ID	Title	Description
OG000	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.
OG001	No Study Treatment Arm	No Isotretinoin treatment

Units	Counts
Participants

Secondary

Change in Cell-associated HIV-1 RNA

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.

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

Posted

Median

Inter-Quartile Range

log10 copies/million CD4 cells

baseline, week 14/16, week 28

ID	Title	Description
OG000	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.
OG001	No Study Treatment Arm

Secondary

Cell-associated HIV-1 DNA

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.

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

Posted

Median

Inter-Quartile Range

log10 copies/million CD4 cells

baseline, week 14/16, week 28

ID	Title	Description
OG000	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.
OG001	No Study Treatment Arm	No Isotretinoin treatment

Secondary

Change in Treg Frequency (%FoxP3+/CD25hi+/CD39+/CD127-(CD4+))

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.

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

Posted

Median

Inter-Quartile Range

percentage of CD4 cells

baseline, week 14/16, week 28

ID	Title	Description
OG000	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.
OG001	No Study Treatment Arm	No Isotretinoin treatment

Units

Secondary

Change in Th17 Frequency (%IFNg-/IL17+(CD161+/CCR6+))

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.

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

Posted

Median

Inter-Quartile Range

percentage of CD161+/CCR6+ cells

baseline, week 14/16, week 28

ID	Title	Description
OG000	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.
OG001	No Study Treatment Arm	No Isotretinoin treatment

Secondary

Pharmacokinetics - Endogenous Levels of Retinoid Metabolites for Isotretinoin Arm

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.

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

Posted

Median

Inter-Quartile Range

nmol/mL

weeks 0, 20, 28

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Pharmacokinetics - Steady-state Trough Concentrations of Isotretinoin for Isotretinoin Arm

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.

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

Posted

Median

Inter-Quartile Range

pmol/mL

weeks 8, 12, 16

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Pharmacokinetics - Trough Concentrations of TDF for Isotretinoin Arm

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.)

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

Posted

Median

Inter-Quartile Range

ng/mL

weeks 0, 8, 12, 16, 20

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Pharmacokinetics - 12-hour Levels of EFV for Isotretinoin Arm

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.)

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

Posted

Median

Inter-Quartile Range

ng/mL

weeks 0, 8, 12, 16, 20

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Primary Targeted Adverse Events

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.

all enrolled participants

Posted

Count of Participants

Participants

from study entry to end of study (week 28)

ID	Title	Description
OG000	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.
OG001	No Study Treatment Arm	No Isotretinoin treatment

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Isotretinoin	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.	0	50	2	50	41	50
EG001	No Study Treatment	No Isotretinoin treatment	0	26	0	26	18	26

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Meningitis viral	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0001 affected50 at risk EG0010 affected26 at risk
Pyelonephritis	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0001 affected50 at risk EG0010 affected26 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected50 at risk EG0012 affected26 at risk
Alanine aminotransferase increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 affected50 at risk EG0014 affected26 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 affected50 at risk EG0013 affected26 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0003 affected50 at risk EG0012 affected26 at risk
Blood bicarbonate decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0003 affected50 at risk EG0011 affected26 at risk
Blood bilirubin increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0007 affected50 at risk EG0012 affected26 at risk
Blood cholesterol increased	Investigations	MedDRA 20.0	Systematic Assessment	EG00020 affected50 at risk EG00111 affected26 at risk
Blood creatinine increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0003 affected50 at risk EG0012 affected26 at risk
Blood glucose decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0003 affected50 at risk EG0011 affected26 at risk
Blood glucose increased	Investigations	MedDRA 20.0	Systematic Assessment	EG00010 affected50 at risk EG0015 affected26 at risk
Blood potassium decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0003 affected50 at risk EG0012 affected26 at risk
Blood sodium decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0003 affected50 at risk EG0011 affected26 at risk
Lipase abnormal	Investigations	MedDRA 20.0	Systematic Assessment	EG0003 affected50 at risk EG0012 affected26 at risk
Low density lipoprotein increased	Investigations	MedDRA 20.0	Systematic Assessment	EG00018 affected50 at risk EG0018 affected26 at risk
Neutrophil count decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0002 affected50 at risk EG0012 affected26 at risk
Platelet count decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0002 affected50 at risk EG0012 affected26 at risk
Headache	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected50 at risk EG0010 affected26 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected50 at risk EG0012 affected26 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected50 at risk EG0010 affected26 at risk

ID	Term
D015474	Isotretinoin

Ancestor Terms

ID	Term
D012176	Retinoids
D002338	Carotenoids
D011090	Polyenes
D000475	Alkenes
D006839	Hydrocarbons, Acyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D053138	Cyclohexenes
D003510	Cyclohexanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D013729	Terpenes
D010860	Pigments, Biological
D001685	Biological Factors

No Isotretinoin treatment