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HIV-1 InfectionPhase 4NCT01777997

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

A Phase 4 study testing Emtricitabine/rilpivirine/tenofovir disoproxil fumarate in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 19 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV-1 Infection
What is being tested?
Emtricitabine/rilpivirine/tenofovir disoproxil fumarate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
19 sitesUnited States
Study dates
25 Apr 2013to 7 Feb 2017
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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

Who cannot join

  • 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
Show all 21Show fewer
  • 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.

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

United States19 sites

  • The Ponce de Leon Ctr. CRS (5802)

    Atlanta, Georgia, 30308

  • IHV Baltimore Treatment CRS (4651)

    Baltimore, Maryland, 21201

  • 31788 Alabama CRS

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital ACTG CRS (101)

    Boston, Massachusetts, 02114

  • Brigham and Women's Hosp. ACTG CRS (107)

    Boston, Massachusetts, 02115

  • Unc Aids Crs (3201)

    Chapel Hill, North Carolina, 27516

  • Northwestern University CRS (2701)

    Chicago, Illinois, 60611

  • Rush Univ. Med. Ctr. ACTG CRS (2702)

    Chicago, Illinois, 60612

  • University of Cincinnati CRS (2401)

    Cincinnati, Ohio, 45267

  • Metro Health CRS (2503)

    Cleveland, Ohio, 44109

  • Moses H. Cone Memorial Hospital CRS (3203)

    Greensboro, North Carolina, 27401

  • Houston AIDS Research Team CRS (31473)

    Houston, Texas, 77030

  • Hosp. of the Univ. of Pennsylvania CRS (6201)

    Philadelphia, Pennsylvania, 19104

  • Pitt CRS (1001)

    Pittsburgh, Pennsylvania, 15213

  • The Miriam Hosp. ACTG CRS (2951)

    Providence, Rhode Island, 02906

  • University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)

    Rochester, New York, 14642

  • 801 University of California, San Francisco HIV/AIDS CRS

    San Francisco, California, 94110

  • Bronx-Lebanon Hosp. Ctr. CRS (31469)

    The Bronx, New York, 10457

  • Whitman Walker Health CRS (31791)

    Washington D.C., District of Columbia, 20009

Other trials in United States

About this study

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

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.

Read the 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.

Conditions
HIV-1 Infection
Being tested
Emtricitabine/rilpivirine/tenofovir disoproxil fumarate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Emtricitabine/rilpivirine/tenofovir disoproxil fumarateDrug

    Also called FTC/RPV/TDF, Complera

    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.

Study groups in NCT01777997
Study groupRoleWhat they receive
FTC/RPV/TDFExperimentalNot described
Receives: Drug: Emtricitabine/rilpivirine/tenofovir disoproxil fumarate

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    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)

    Measured: From baseline (pre-ART and week 0 on ART) to weeks 24 and 48 on ART

Secondary outcomes (8)

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

    Measured: At pre-ART and weeks 0, 4, 12, 24, 36 and 48 on ART

  2. Change in CD4+ T-cell Count

    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)

    Measured: From baseline (pre-ART and week 0 on ART) to weeks 12, 24, 36 and 48 on ART

  3. Change in Levels of CD8+ T-cell Activation

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

    Measured: From baseline (pre-ART and week 0 on ART) to weeks 4, 12, 24 and 48 on ART

  4. Change in Levels of CD4+ T-cell Activation (Defined as the Percentage HLA-DR+/CD38+)

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

    Measured: From baseline (pre-ART and week 0 on ART) to weeks 4, 12, 24 and 48 on ART

  5. Change in Levels of Interleukin (IL)-6

    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)

    Measured: From baseline (pre-ART and week 0 on ART) to weeks 4, 12, 24 and 48 on ART

  6. Change in Levels of D-dimer

    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)

    Measured: From baseline (pre-ART and week 0 on ART) to weeks 4, 24 and 48 on ART

  7. Change in Quality of Life (QoL) Index

    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)

    Measured: From baseline (pre-ART and week 0 on ART) to weeks 4, 24 and 48 on 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)

    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.

    Measured: From initiation of treatment to study completion at week 60 or 108 or premature study discontinuation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jan 2013 (estimated)
  2. Study start25 Apr 2013
  3. Primary completion19 Feb 2016
  4. Study completion7 Feb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01777997
Sponsor's protocol ID
ACTG A5308
Other IDs
1U01AI068636
Status last verified
Dec 2017
First submitted
10 Jan 2013
Last updated
3 Aug 2021
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Emtricitabine/rilpivirine/tenofovir disoproxil fumarate in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Levels of CD8+ T-cell Activation (Defined as the Percentage HLA-DR+/CD38+) From Baseline to Weeks 24 and 48 on ART (time frame: From baseline (pre-ART and week 0 on ART) to weeks 24 and 48 on ART). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01777997.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2021.

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