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

This study is currently recruiting participants.
Verified December 2013 by AIDS Clinical Trials Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01777997
First received: January 10, 2013
Last updated: December 5, 2013
Last verified: December 2013
  Purpose

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

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


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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by AIDS Clinical Trials Group:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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)


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 57
Study Start Date: February 2013
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fixed dose combination FTC/RPV/TDF for 48 or 96 weeks

Step 1 From entry through week 12 the participants will receive no study treatment. From week 12 through week 60, the participants will receive one FTC/RPV/TDF (200mg/25mg/300mg) tablet orally once daily with a meal.

Step 2 (Optional) From week 60 through Week 108, the participants will either receive one FTC/RPV/TDF (200mg/25mg/300mg)table orally once daily with a meal or no study treatment.

Drug: Emtricitabine/rilpivirine/tenofovir disoproxil fumarate
Other Names:
  • FTC/RPV/TDF
  • Complera

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Step 1

  • HIV-1 infection
  • ART-naïve defined as ≤7 days of 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/mm3
    • Hemoglobin >=8.0 g/dL
    • Platelet count >=40,000/mm3
    • 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 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 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 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 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01777997

  Show 29 Study Locations
Sponsors and Collaborators
AIDS Clinical Trials Group
  More Information

No publications provided

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01777997     History of Changes
Other Study ID Numbers: ACTG A5308, 1U01AI068636
Study First Received: January 10, 2013
Last Updated: December 5, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Tenofovir
Tenofovir disoproxil
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on April 14, 2014