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

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ClinicalTrials.gov Identifier: NCT01777997
Recruitment Status : Completed
First Posted : January 29, 2013
Results First Posted : January 12, 2018
Last Update Posted : January 12, 2018
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group

January 10, 2013
January 29, 2013
October 31, 2017
January 12, 2018
January 12, 2018
April 25, 2013
February 19, 2016   (Final data collection date for 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 ]
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)
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 to week 48 on ART ]
Change from baseline (average of study entry and study week 12), estimated with a repeated measures analysis (weeks 24 and 48 on ART) using generalized estimating equations (GEE)
Complete list of historical versions of study NCT01777997 on ClinicalTrials.gov Archive Site
  • 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 [ Time Frame: 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)
  • Change in CD4+ T-cell Count [ Time Frame: 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)
  • Change in Levels of CD8+ T-cell Activation [ Time Frame: 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)
  • Change in Levels of CD4+ T-cell Activation (Defined as the Percentage HLA-DR+/CD38+) [ Time Frame: 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)
  • Change in Levels of Interleukin (IL)-6 [ Time Frame: 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)
  • Change in Levels of D-dimer [ Time Frame: 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)
  • Change in Quality of Life (QoL) Index [ Time Frame: 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)
  • Number of Subjects Who Experience Grade 3 or 4 Signs and Symptoms or Laboratory Abnormalities, Diagnoses (Any Grade), or Other Serious Adverse Events (SAEs) [ Time Frame: 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.
  • Plasma HIV-1 RNA level measured by Single Copy Assay (SCA) as above versus below the limit of the assay [ Time Frame: At baseline and weeks 4, 12, 24, 36 and 48 on ART ]
    At a specific week, the proportion of subjects with HIV-1 RNA by SCA < assay limit
  • Change in CD4+ T-cell Count [ Time Frame: From baseline 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 (average of study entry and study week 12)
  • Change in Levels of CD8+ T-cell Activation [ Time Frame: From baseline to weeks 4, 24 and 48 on ART ]
    Change equals each specific week percentage, respectively, minus the baseline percentage (average of study entry and study week 12)
  • Change in Levels of CD4+ T-cell Activation (Defined as the Percentage HLA-DR+/CD38+) [ Time Frame: From baseline to weeks 4, 24 and 48 on ART ]
    Change equals each specific week percentage, respectively, minus the baseline percentage (average of study entry and study week 12)
  • Change in Levels of Interleukin (IL)-6 [ Time Frame: From baseline to weeks 4, 24 and 48 on ART ]
    Change equals each specific week result, respectively, minus the baseline result (average of study entry and study week 12)
  • Change in levels of 2D-dimer [ Time Frame: From baseline to weeks 4, 24 and 48 on ART ]
    Change equals each specific week result, respectively, minus the baseline result (average of study entry and study week 12)
  • Change in Quality of Life (QoL) Index [ Time Frame: From baseline to weeks 4, 24 and 48 on ART ]
    The QoL index is obtained by averaging the five responses on the Euro-Quality of Life questionnaire (EQ-5D). Change equals each specific week index, respectively, minus the baseline index (average of study entry and study week 12)
  • Number of subjects who experience Grade 3 or 4 signs and symptoms or laboratory abnormalities, diagnoses, or other serious adverse events (SAEs) [ Time Frame: From baseline through week 48 on ART ]
    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.
Not Provided
Not Provided
 
FTC/RPV/TDF on T-Cell Activation, CD4+ T-Cell Count, Inflammatory Biomarkers and Viral Reservoir
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.

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.

Interventional
Phase 4
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
HIV-1 Infection
Drug: Emtricitabine/rilpivirine/tenofovir disoproxil fumarate
Other Names:
  • FTC/RPV/TDF
  • Complera
Experimental: FTC/RPV/TDF

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.

Intervention: Drug: Emtricitabine/rilpivirine/tenofovir disoproxil fumarate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
38
57
February 7, 2017
February 19, 2016   (Final data collection date for primary outcome measure)

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.

Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01777997
ACTG A5308
1U01AI068636 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Not Provided
AIDS Clinical Trials Group
AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: Jonathan Li, M.D., M.M.S. Brigham and Women's Hospital Therapeutics (BWHT) CRS
AIDS Clinical Trials Group
December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP