FTC/RPV/TDF on T-Cell Activation, CD4+ T-Cell Count, Inflammatory Biomarkers and Viral Reservoir

• Sponsor: AIDS Clinical Trials Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT01777997
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Enrollment: 38
• Locations: 19
• Arm: 1
• Actual Duration (Months): 45.5
• Patients Per Site: 2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study was done with people who were infected with HIV, but did not show any signs of having HIV. They were also feeling well without taking HIV medication and had low or undetectable levels of the virus in the blood. The purpose of this study was to see if taking HIV medication (antiretroviral therapy [ART]) would reduce immune activation (a signal that the body is fighting an infection) in people who have HIV, but did not show symptoms. Also this study helped determine how safe the drug was and how well people reacted to the drug.

For this study, the following antiretroviral therapy (ART) was be provided in the form of a single tablet that contains three different drugs: emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF). These drugs were combined as one tablet which was approved by the Food and Drug Administration (FDA) as a single pill to treat HIV infection. The HIV medication provided was one of the recommended treatments for HIV, including people with low viral loads (how much HIV you have in your body) who were taking HIV drugs for the first time. The risks seen with this HIV medication were the same that one would encounter when taking these drugs outside of the study.

Condition or Disease	Intervention/Treatment	Phase
HIV-1 Infection	Drug: Emtricitabine/rilpivirine/tenofovir disoproxil fumarate	Phase 4

Detailed Description

AIDS Clinical Trials Group (ACTG) A5308 was a single-arm clinical trial to evaluate the effect of initiating fixed-dose combination (FDC) FTC/RPV/TDF on CD8+ T-cell activation and other immunologic and virologic biomarkers among treatment-naïve HIV-1 controllers with any absolute CD4+ T-cell count. At study entry, these participants were followed off ART for a 12-week lead-in period, and then at week 12, participants initiated FDC FTC/RPV/TDF and had 48 weeks of follow-up to evaluate the primary endpoint.

All participants who completed Step 1 (48 weeks of ART) had the option to register to Step 2, for an additional 48 weeks of follow-up, and had the choice of either continuing FDC FTC/RPV/TDF or follow-up with no study treatment.

Participants underwent safety and tolerability evaluations throughout the study, including physical examinations and clinical assessments. Pregnancy tests were performed on women of childbearing potential. Collection of stored blood plasma/peripheral blood mononuclear cell (PBMC) samples occurred at entry and weeks 0, 4, 12, 24, 36, 48, 60, 72 and 96 on ART.

Only participants who were on intervention (ART) for at least 24 weeks had samples sent for testing of immunologic and virologic biomarkers.

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Single-Arm, Open-Label Study to Evaluate the Effect of Fixed-Dose Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate on T-Cell Activation, Absolute CD4+ T-Cell Count, Inflammatory Biomarkers and Viral Reservoir in Treatment-Naïve HIV-1 Controllers
• Actual Study Start Date: Apr 25, 2013
• Actual Primary Completion Date: Feb 19, 2016
• Actual Study Completion Date: Feb 7, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: FTC/RPV/TDF

Drug: Emtricitabine/rilpivirine/tenofovir disoproxil fumarate; Step 1: From entry through week 12, the participants received no study treatment. From week 12 through week 60, the participants received one fixed dose combination emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) tablet daily. Step 2 (Optional): From week 60 through week 108, the participants either received one FTC/RPV/TDF tablet daily or no study treatment.; Other Names: FTC/RPV/TDF Complera

Outcome Measures

Primary Outcome Measures

1. Change in Levels of CD8+ T-cell Activation (Defined as the Percentage HLA-DR+/CD38+) From Baseline to Weeks 24 and 48 on ART [From baseline (pre-ART and week 0 on ART) to weeks 24 and 48 on ART]

   Mean change from baseline (pre-ART [study entry] and week 0 on ART [study week 12]), estimated with a repeated measures analysis (jointly to weeks 24 and 48 on ART) using generalized estimating equations (GEE)

Secondary Outcome Measures

1. Plasma HIV-1 RNA Level Measured by Single Copy Assay Using Primer in Integrase (iSCA) as the Proportion of Participants Below the Limit of the Assay [At pre-ART and weeks 0, 4, 12, 24, 36 and 48 on ART]

   At a specific week, the proportion of participants with HIV-1 RNA by iSCA less than assay limit of detection (0.6 copies/mL)

2. Change in CD4+ T-cell Count [From baseline (pre-ART and week 0 on ART) to weeks 12, 24, 36 and 48 on ART]

   Change equals each specific week CD4+ T-cell count, respectively, minus the baseline CD4+ T-cell count (mean of the two measurements obtained prior to the start of ART)

3. Change in Levels of CD8+ T-cell Activation [From baseline (pre-ART and week 0 on ART) to weeks 4, 12, 24 and 48 on ART]

   Change equals each specific week percentage, respectively, minus the baseline percentage (mean of the two measurements obtained prior to the start of ART)

4. Change in Levels of CD4+ T-cell Activation (Defined as the Percentage HLA-DR+/CD38+) [From baseline (pre-ART and week 0 on ART) to weeks 4, 12, 24 and 48 on ART]

   Change equals each specific week percentage, respectively, minus the baseline percentage (mean of the two measurements obtained prior to the start of ART)

5. Change in Levels of Interleukin (IL)-6 [From baseline (pre-ART and week 0 on ART) to weeks 4, 12, 24 and 48 on ART]

   Change equals each specific week result, respectively, minus the baseline result (mean of the two log10-transformed measurements obtained prior to the start of ART)

6. Change in Levels of D-dimer [From baseline (pre-ART and week 0 on ART) to weeks 4, 24 and 48 on ART]

   Change equals each specific week result, respectively, minus the baseline result (mean of the two log10-transformed measurements obtained prior to the start of ART)

7. Change in Quality of Life (QoL) Index [From baseline (pre-ART and week 0 on ART) to weeks 4, 24 and 48 on ART]

   QoL index was obtained by averaging the five responses on the Euro-Quality of Life questionnaire (EQ-5D), where a response of 0 indicates "no problems/no discomfort", 1 indicates "some problems/moderate discomfort" and 2 indicates "unable to perform activities/extreme discomfort". Change equals each specific week index, respectively, minus the baseline index (mean of the two averages obtained prior to the start of ART)

8. Number of Subjects Who Experience Grade 3 or 4 Signs and Symptoms or Laboratory Abnormalities, Diagnoses (Any Grade), or Other Serious Adverse Events (SAEs) [From initiation of treatment to study completion at week 60 or 108 or premature study discontinuation]

   Grading uses the Division of AIDS (DAIDS) 2004 (clarification 2009) Severity of Adverse Events Table, where Grade 1=Mild, 2=Moderate, 3=Severe, 4=Potentially life-threatening.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Step 1

• HIV-1 infection

• ART-naïve defined as ≤7 days of antiretroviral (ARV) treatment at any time prior to entry

• Documentation of HIV-1 RNA <500 copies/mL verified by at least two measurements prior to the screening RNA specimen

• Screening HIV-1 RNA <500 copies/mL using an US FDA-approved assay obtained within 60 days prior to study entry by any laboratory that has a CLIA certification or its equivalent

• Laboratory values obtained within 60 days prior to entry by any laboratory that has a

CLIA certification or its equivalent:

• Absolute neutrophil count (ANC) >=500/mm^3

• Hemoglobin >=8.0 g/dL

• Platelet count >=40,000/mm^3

• Aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), and alkaline phosphatase <=5 X Upper Limit of Normal (ULN)

• Total bilirubin <=2.5 X ULN

• Calculated creatinine clearance (CrCl) >=60 mL/min

• For females of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to study entry by any clinic or laboratory that has a CLIA certification or its equivalent

• Female subjects of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree to use at least one reliable form of contraceptive (ie, condoms (male or female) with or without a spermicidal agent; a diaphragm or cervical cap with spermicide; an intrauterine device (IUD); or hormone-based contraceptive) while receiving the protocol-specified treatment and for 6 weeks after stopping the medications

• No evidence of any exclusionary resistance mutations based on results from any genotype assay from any laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent

Step 2

• Completion of Step 1

• Ability and willingness of subject to choose to receive either open-label ART FDC (FTC/RPV/TDF) or no study treatment for an additional 48 weeks

• For females of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to the week 60 visit by any clinic or laboratory that has a CLIA certification or its equivalent

Exclusion Criteria:

Step 1

• Chronic hepatitis B virus (HBV) infection (documented by hepatitis B surface antigen (HBsAg) seropositivity)

• Breastfeeding

• Use of immunomodulators (eg, interleukins, interferons, cyclosporine), topical imiquimod, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry or plans to start immunomodulators, topical imiquimod, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy during the study

• Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation

• 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 30 days prior to entry

• Symptomatic HIV disease and/or AIDS-defining illness.

• Vaccinations within 7 days prior to study entry

• Plans to initiate hepatitis C treatment during the study

• Perinatally-acquired HIV

• Use of any of the following medications within 7 days prior to study entry:

• St. John's wort (Hypercium perforatum)

• Anticonvulsants (eg, oxacarbazepine, phenobarbital, phenytoin)

• Anti-infectives (eg, rifabutin, rifampin, rifapentine)

• Corticosteroids (eg, dexamethasone (more than 1 dose))

• Proton pump inhibitors (eg, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole)

Step 2

• Plans to start immunomodulators, topical imiquimod, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy during Step 2 of the study

• Plans to initiate hepatitis C treatment during Step 2 of the study

NOTE: Please refer to the protocol for detailed eligibility criteria.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	31788 Alabama CRS	Birmingham	Alabama	United States	35294
2	801 University of California, San Francisco HIV/AIDS CRS	San Francisco	California	United States	94110
3	Whitman Walker Health CRS (31791)	Washington	District of Columbia	United States	20009
4	The Ponce de Leon Ctr. CRS (5802)	Atlanta	Georgia	United States	30308
5	Northwestern University CRS (2701)	Chicago	Illinois	United States	60611
6	Rush Univ. Med. Ctr. ACTG CRS (2702)	Chicago	Illinois	United States	60612
7	IHV Baltimore Treatment CRS (4651)	Baltimore	Maryland	United States	21201
8	Massachusetts General Hospital ACTG CRS (101)	Boston	Massachusetts	United States	02114
9	Brigham and Women's Hosp. ACTG CRS (107)	Boston	Massachusetts	United States	02115
10	Bronx-Lebanon Hosp. Ctr. CRS (31469)	Bronx	New York	United States	10457
11	University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)	Rochester	New York	United States	14642
12	Unc Aids Crs (3201)	Chapel Hill	North Carolina	United States	27516
13	Moses H. Cone Memorial Hospital CRS (3203)	Greensboro	North Carolina	United States	27401
14	University of Cincinnati CRS (2401)	Cincinnati	Ohio	United States	45267
15	Metro Health CRS (2503)	Cleveland	Ohio	United States	44109
16	Hosp. of the Univ. of Pennsylvania CRS (6201)	Philadelphia	Pennsylvania	United States	19104
17	Pitt CRS (1001)	Pittsburgh	Pennsylvania	United States	15213
18	The Miriam Hosp. ACTG CRS (2951)	Providence	Rhode Island	United States	02906
19	Houston AIDS Research Team CRS (31473)	Houston	Texas	United States	77030

Sponsors and Collaborators

• AIDS Clinical Trials Group
• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Chair: Jonathan Li, M.D., M.M.S., Brigham and Women's Hospital Therapeutics (BWHT) CRS

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009)
• Requirements, definitions, and methods for expedited reporting of Adverse Events (AEs) in Version 2.0 of the DAIDS EAE Manual

Publications

None provided.

• Responsible Party: AIDS Clinical Trials Group
• ClinicalTrials.gov Identifier: NCT01777997
• Other Study ID Numbers: ACTG A5308; 1U01AI068636
• First Posted: Jan 29, 2013
• Last Update Posted: Aug 3, 2021
• Last Verified: Dec 1, 2017

• Additional relevant MeSH terms: Tenofovir; Emtricitabine; Rilpivirine

Study Results

Participant Flow

Recruitment Details	Recruited at 19 Clinical Research Sites (CRSs) in the United States between April 25, 2013 and December 22, 2014.

Arm/Group Title	FTC/RPV/TDF
Arm/Group Description	Step 1: From entry through week 12, the participants received no study treatment. From week 12 through week 60, the participants received one fixed dose combination emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) tablet daily. Participants in the primary outcome analysis were on ART for at least 24 weeks and up to 48 weeks. Step 2 (Optional): From week 60 through week 108, the participants either received one FTC/RPV/TDF tablet daily or no study treatment. Participants in exploratory analyses were on ART for at least 72 weeks and up to 96 weeks.
Period Title: 12 Week lead-in of no ART
STARTED	38
COMPLETED	36
NOT COMPLETED	2
Period Title: 12 Week lead-in of no ART
STARTED	36
COMPLETED	35
NOT COMPLETED	1
Period Title: 12 Week lead-in of no ART
STARTED	28
COMPLETED	26
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	FTC/RPV/TDF
Arm/Group Description	Step 1: From entry through week 12, the participants received no study treatment. From week 12 through week 60, the participants received one fixed dose combination emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) tablet daily. Step 2 (Optional): From week 60 through week 108, the participants either received one FTC/RPV/TDF tablet daily or no study treatment.
Overall Participants	35
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	47
Sex: Female, Male (Count of Participants)
Female	15 42.9%
Male	20 57.1%
Race/Ethnicity, Customized (participants) [Number]
White non-Hispanic	6 17.1%
Black non-Hispanic	26 74.3%
Hispanic (regardless of race)	3 8.6%
Region of Enrollment (participants) [Number]
United States	35 100%
CD4+ T-cell count (cells/mm^3) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cells/mm^3]	682
HIV-1 RNA by Abbott Assay (Count of Participants)
<40 copies/mL	16 45.7%
>=40 copies/mL	19 54.3%
<40 copies/mL	13 37.1%
>=40 copies/mL	22 62.9%
Percentage of CD8+ T-cells that are CD38+HLA-DR+ (% of CD8+ T-cells) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [% of CD8+ T-cells]	24.6
Percentage of CD4+ T-cells that are CD38+HLA-DR+ (% of CD4+ T-cells) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [% of CD4+ T-cells]	2.6
Interleukin (IL)-6 (log10(pg/mL)) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [log10(pg/mL)]	0.17
D-dimer (log10(ng/mL)) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [log10(ng/mL)]	2.58
Quality of life (QoL) index (units on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [units on a scale]	0.2

Outcome Measures

1. Primary Outcome

Title	Change in Levels of CD8+ T-cell Activation (Defined as the Percentage HLA-DR+/CD38+) From Baseline to Weeks 24 and 48 on ART
Description	Mean change from baseline (pre-ART [study entry] and week 0 on ART [study week 12]), estimated with a repeated measures analysis (jointly to weeks 24 and 48 on ART) using generalized estimating equations (GEE)
Time Frame	From baseline (pre-ART and week 0 on ART) to weeks 24 and 48 on ART

Outcome Measure Data

Analysis Population Description

As-treated: Only participants with results while receiving intervention (ART) and suppressed HIV-1 RNA <200 copies/mL for at least 2 weeks (14 days) prior to week 24 or 48 weeks on ART (and without use of prohibited or precautionary medications based on team review of concomitant medications) were included.

Arm/Group Title	FTC/RPV/TDF
Arm/Group Description	Step 1: From entry through week 12, the participants received no study treatment. From week 12 through week 60, the participants received one fixed dose combination emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) tablet daily. Step 2 (Optional): From week 60 through week 108, the participants either received one FTC/RPV/TDF tablet daily or no study treatment.
Measure Participants	35
Mean (95% Confidence Interval) [% of CD8+ T-cells]	-4.01

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FTC/RPV/TDF
	Comments	Estimated mean change from baseline to weeks 24-48 on ART from repeated measures (GEE) model, against the null hypothesis of zero change. Estimated mean represents on ART levels minus pre-ART levels.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Regression, repeated measures (GEE)
	Comments

2. Secondary Outcome

Title	Plasma HIV-1 RNA Level Measured by Single Copy Assay Using Primer in Integrase (iSCA) as the Proportion of Participants Below the Limit of the Assay
Description	At a specific week, the proportion of participants with HIV-1 RNA by iSCA less than assay limit of detection (0.6 copies/mL)
Time Frame	At pre-ART and weeks 0, 4, 12, 24, 36 and 48 on ART

Outcome Measure Data

Analysis Population Description

As-treated: Only participants with results while receiving intervention (ART) and suppressed HIV-1 RNA <200 copies/mL for at least 2 weeks (14 days) prior to measured weeks on ART (and without use of prohibited or precautionary medications based on team review of concomitant medications) were included.

Arm/Group Title	FTC/RPV/TDF
Arm/Group Description	Step 1: From entry through week 12, the participants received no study treatment. From week 12 through week 60, the participants received one fixed dose combination emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) tablet daily. Step 2 (Optional): From week 60 through week 108, the participants either received one FTC/RPV/TDF tablet daily or no study treatment.
Measure Participants	35
Pre-ART	0.19 0.5%
Week 0 on ART	0.19 0.5%
Week 4 on ART	0.61 1.7%
Week 12 on ART	0.90 2.6%
Week 24 on ART	0.93 2.7%
Week 36 on ART	0.92 2.6%
Week 48 on ART	0.96 2.7%

3. Secondary Outcome

Title	Change in CD4+ T-cell Count
Description	Change equals each specific week CD4+ T-cell count, respectively, minus the baseline CD4+ T-cell count (mean of the two measurements obtained prior to the start of ART)
Time Frame	From baseline (pre-ART and week 0 on ART) to weeks 12, 24, 36 and 48 on ART

Outcome Measure Data

Analysis Population Description

As-treated: Only participants with results while receiving intervention (ART) and suppressed HIV-1 RNA <200 copies/mL for at least 2 weeks (14 days) prior to measured weeks on ART (and without use of prohibited or precautionary medications based on team review of concomitant medications) were included.

Arm/Group Title	FTC/RPV/TDF
Arm/Group Description	Step 1: From entry through week 12, the participants received no study treatment. From week 12 through week 60, the participants received one fixed dose combination emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) tablet daily. Step 2 (Optional): From week 60 through week 108, the participants either received one FTC/RPV/TDF tablet daily or no study treatment.
Measure Participants	35
Week 12 on ART	-15
Week 24 on ART	-5
Week 36 on ART	25
Week 48 on ART	19

4. Secondary Outcome

Title	Change in Levels of CD8+ T-cell Activation
Description	Change equals each specific week percentage, respectively, minus the baseline percentage (mean of the two measurements obtained prior to the start of ART)
Time Frame	From baseline (pre-ART and week 0 on ART) to weeks 4, 12, 24 and 48 on ART

Outcome Measure Data

Analysis Population Description

As-treated: Only participants with results while receiving intervention (ART) and suppressed HIV-1 RNA <200 copies/mL for at least 2 weeks (14 days) prior to measured weeks on ART (and without use of prohibited or precautionary medications based on team review of concomitant medications) were included.

Arm/Group Title	FTC/RPV/TDF
Arm/Group Description	Step 1: From entry through week 12, the participants received no study treatment. From week 12 through week 60, the participants received one fixed dose combination emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) tablet daily. Step 2 (Optional): From week 60 through week 108, the participants either received one FTC/RPV/TDF tablet daily or no study treatment.
Measure Participants	35
Week 4 on ART	-0.7
Week 12 on ART	-1.6
Week 24 on ART	-2.2
Week 48 on ART	-4.7

5. Secondary Outcome

Title	Change in Levels of CD4+ T-cell Activation (Defined as the Percentage HLA-DR+/CD38+)
Description	Change equals each specific week percentage, respectively, minus the baseline percentage (mean of the two measurements obtained prior to the start of ART)
Time Frame	From baseline (pre-ART and week 0 on ART) to weeks 4, 12, 24 and 48 on ART

Outcome Measure Data

Analysis Population Description

As-treated: Only participants with results while receiving intervention (ART) and suppressed HIV-1 RNA <200 copies/mL for at least 2 weeks (14 days) prior to measured weeks on ART (and without use of prohibited or precautionary medications based on team review of concomitant medications) were included.

Arm/Group Title	FTC/RPV/TDF
Arm/Group Description	Step 1: From entry through week 12, the participants received no study treatment. From week 12 through week 60, the participants received one fixed dose combination emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) tablet daily. Step 2 (Optional): From week 60 through week 108, the participants either received one FTC/RPV/TDF tablet daily or no study treatment.
Measure Participants	35
Week 4 on ART	0.1
Week 12 on ART	-0.1
Week 24 on ART	-0.2
Week 48 on ART	-0.2

6. Secondary Outcome

Title	Change in Levels of Interleukin (IL)-6
Description	Change equals each specific week result, respectively, minus the baseline result (mean of the two log10-transformed measurements obtained prior to the start of ART)
Time Frame	From baseline (pre-ART and week 0 on ART) to weeks 4, 12, 24 and 48 on ART

Outcome Measure Data

Analysis Population Description

As-treated: Only participants with results while receiving intervention (ART) and suppressed HIV-1 RNA <200 copies/mL for at least 2 weeks (14 days) prior to measured weeks on ART (and without use of prohibited or precautionary medications based on team review of concomitant medications) were included.

Arm/Group Title	FTC/RPV/TDF
Arm/Group Description	Step 1: From entry through week 12, the participants received no study treatment. From week 12 through week 60, the participants received one fixed dose combination emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) tablet daily. Step 2 (Optional): From week 60 through week 108, the participants either received one FTC/RPV/TDF tablet daily or no study treatment.
Measure Participants	35
Week 4 on ART	0.05
Week 12 on ART	0.01
Week 24 on ART	0.02
Week 48 on ART	0

7. Secondary Outcome

Title	Change in Levels of D-dimer
Description	Change equals each specific week result, respectively, minus the baseline result (mean of the two log10-transformed measurements obtained prior to the start of ART)
Time Frame	From baseline (pre-ART and week 0 on ART) to weeks 4, 24 and 48 on ART

Outcome Measure Data

Analysis Population Description

As-treated: Only participants with results while receiving intervention (ART) and suppressed HIV-1 RNA <200 copies/mL for at least 2 weeks (14 days) prior to measured weeks on ART (and without use of prohibited or precautionary medications based on team review of concomitant medications) were included.

Arm/Group Title	FTC/RPV/TDF
Arm/Group Description	Step 1: From entry through week 12, the participants received no study treatment. From week 12 through week 60, the participants received one fixed dose combination emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) tablet daily. Step 2 (Optional): From week 60 through week 108, the participants either received one FTC/RPV/TDF tablet daily or no study treatment.
Measure Participants	35
Week 4 on ART	0.01
Week 24 on ART	0.01
Week 48 on ART	0.02

8. Secondary Outcome

Title	Change in Quality of Life (QoL) Index
Description	QoL index was obtained by averaging the five responses on the Euro-Quality of Life questionnaire (EQ-5D), where a response of 0 indicates "no problems/no discomfort", 1 indicates "some problems/moderate discomfort" and 2 indicates "unable to perform activities/extreme discomfort". Change equals each specific week index, respectively, minus the baseline index (mean of the two averages obtained prior to the start of ART)
Time Frame	From baseline (pre-ART and week 0 on ART) to weeks 4, 24 and 48 on ART

Outcome Measure Data

Analysis Population Description

As-treated: Only participants with results while receiving intervention (ART) and suppressed HIV-1 RNA <200 copies/mL for at least 2 weeks (14 days) prior to measured weeks on ART (and without use of prohibited or precautionary medications based on team review of concomitant medications) were included.

Arm/Group Title	FTC/RPV/TDF
Arm/Group Description	Step 1: From entry through week 12, the participants received no study treatment. From week 12 through week 60, the participants received one fixed dose combination emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) tablet daily. Step 2 (Optional): From week 60 through week 108, the participants either received one FTC/RPV/TDF tablet daily or no study treatment.
Measure Participants	35
Week 4 on ART	0
Week 24 on ART	-0.1
Week 48 on ART	0

9. Secondary Outcome

Title	Number of Subjects Who Experience Grade 3 or 4 Signs and Symptoms or Laboratory Abnormalities, Diagnoses (Any Grade), or Other Serious Adverse Events (SAEs)
Description	Grading uses the Division of AIDS (DAIDS) 2004 (clarification 2009) Severity of Adverse Events Table, where Grade 1=Mild, 2=Moderate, 3=Severe, 4=Potentially life-threatening.
Time Frame	From initiation of treatment to study completion at week 60 or 108 or premature study discontinuation

Outcome Measure Data

Analysis Population Description

All participants who initiated ART, regardless of ART status at time of event

Arm/Group Title	FTC/RPV/TDF
Arm/Group Description	Step 1: From entry through week 12, the participants received no study treatment. From week 12 through week 60, the participants received one fixed dose combination emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) tablet daily. Step 2 (Optional): From week 60 through week 108, the participants either received one FTC/RPV/TDF tablet daily or no study treatment.
Measure Participants	36
Number [participants]	18 51.4%

Adverse Events

Time Frame	From initiation of treatment to study completion at week 60 or 108 or premature study discontinuation
Adverse Event Reporting Description	The study protocol required reporting of grade>=3 signs/symptoms, grade>=3 laboratory events and all signs/symptoms and laboratory events that lead to a change in study treatment, as well as diagnoses identified by the ACTG criteria for clinical events and other diseases. See DAIDS AE Grading Table (V1.0), December 2004 (Clarification, August 2009) and EAE manual (V2.0). All participants who initiated study treatment were included.
Arm/Group Title	FTC/RPV/TDF
Arm/Group Description	Step 1: From entry through week 12, the participants received no study treatment. From week 12 through week 60, the participants received one fixed dose combination emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) tablet daily. Step 2 (Optional): From week 60 through week 108, the participants either received one FTC/RPV/TDF tablet daily or no study treatment.
All Cause Mortality
	FTC/RPV/TDF
	Affected / at Risk (%)	# Events
Total	1/36 (2.8%)
Serious Adverse Events
	FTC/RPV/TDF
	Affected / at Risk (%)	# Events
Total	1/36 (2.8%)
Infections and infestations
Bronchitis	1/36 (2.8%)
Other (Not Including Serious) Adverse Events
	FTC/RPV/TDF
	Affected / at Risk (%)	# Events
Total	23/36 (63.9%)
Eye disorders
Eye pruritus	2/36 (5.6%)
Gastrointestinal disorders
Abdominal pain upper	3/36 (8.3%)
Diarrhoea	3/36 (8.3%)
Nausea	4/36 (11.1%)
Proctalgia	2/36 (5.6%)
Vomiting	4/36 (11.1%)
General disorders
Fatigue	2/36 (5.6%)
Peripheral swelling	2/36 (5.6%)
Pyrexia	2/36 (5.6%)
Infections and infestations
Acarodermatitis	2/36 (5.6%)
Bacterial vaginosis	3/36 (8.3%)
Investigations
Alanine aminotransferase increased	5/36 (13.9%)
Aspartate aminotransferase increased	4/36 (11.1%)
Blood bilirubin increased	3/36 (8.3%)
Blood creatinine increased	3/36 (8.3%)
Blood glucose increased	2/36 (5.6%)
Blood phosphorus decreased	5/36 (13.9%)
Blood sodium decreased	5/36 (13.9%)
Neutrophil count decreased	4/36 (11.1%)
Platelet count decreased	2/36 (5.6%)
Metabolism and nutrition disorders
Decreased appetite	3/36 (8.3%)
Nervous system disorders
Syncope	2/36 (5.6%)
Reproductive system and breast disorders
Vaginal discharge	3/36 (8.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/36 (8.3%)
Nasal congestion	3/36 (8.3%)
Oropharyngeal pain	3/36 (8.3%)
Productive cough	3/36 (8.3%)
Skin and subcutaneous tissue disorders
Erythema	2/36 (5.6%)
Pruritus	2/36 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.