Study of Viral Load Decay Rates in HIV Infected Participants Starting Treatment With Raltegravir (RAL) and Emtricitabine/Tenofovir Disoproxil Fumarate (TDF)

First-Phase Viral Decay Rates in Treatment-Naive Subjects Initiating Treatment With Raltegravir (RAL) and Emtricitabine (FTC)/Tenofovir Disoproxil Fumarate (TDF): A Pilot Study

The HIV integrase inhibitor, raltegravir (RAL), which was recently approved by the FDA, has been shown in several trials to be highly effective. The purpose of this trial is to estimate the viral load decay rate in treatment-naive HIV infected participants receiving RAL and emtricitabine/tenofovir disoproxil fumarate (FTC/TDF).

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Raltegravir; Drug: Emtricitabine/tenofovir disoproxil fumarate

Detailed Description

Recent data suggests that early virologic response to HIV interventions may be predictive of long-term virologic outcomes. Defining early decay in viral load through carefully performed studies of viral dynamics may be a useful tool for assessing the likely outcome of long-term treatment. It may also be a useful screening tool to define which combinations should be studied further. In this trial, the viral load decay rate will be estimated in HIV infected, treatment-naive participants receiving RAL and FTC/TDF.

This study will last approximately 72 weeks. All participants will take RAL and FTC/TDF for 72 weeks. RAL will be provided by the study. FTC/TDF will not be provided.

This study will consist of 16 study visits. These visits will occur at study entry, Days 2, 7, 10, 14, 21, 28, and 56, and Weeks 12, 16, 20, 24, 36, 48, 60, and 72. Blood collection and pharmacokinetic studies will occur at all study visits. Self-reported adherence assessments will be submitted at each visit. A targeted physical exam will occur at most visits. Liver function tests and urine collection will occur at select visits. Pregnancy tests will occur whenever pregnancy is suspected.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • UCSD Antiviral Research Center CRS
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital CRS
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University CRS
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University CRS
    • Baltimore, Maryland, United States, 21201
      • IHV Baltimore Treatment CRS
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS
  • Missouri
    • Saint Louis, Missouri, United States, 63110-1010
      • Washington University Therapeutics (WT) CRS
  • New York
    • New York, New York, United States, 10037
      • Harlem ACTG CRS
    • Rochester, New York, United States, 14642
      • Univ. of Rochester ACTG CRS
    • Rochester, New York, United States, 14607
      • Trillium Health ACTG CRS
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth CRS
    • Columbus, Ohio, United States, 43210
      • Ohio State University CRS
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital Clinical Research Site (TMH CRS) CRS
  • Tennessee
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt Therapeutics (VT) CRS
  • Texas
    • Houston, Texas, United States, 77030
      • Houston AIDS Research Team CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV infected
• Antiretroviral treatment naive
• Viral load at least 10,000 and less than 300,000 copies/ml within 42 days prior to study entry
• Agree to use appropriate form of contraception. More information on this criterion can be found in the protocol.

Exclusion Criteria:

• Received HIV-specific immunizations within 6 months prior to study entry
• Received immunizations within 6 months prior to study entry
• Known allergy or sensitivity to study drugs
• Any participant with an acute AIDS-defining opportunistic infection (OI) who is not clinically stable or who has not been on therapy for the OI for at least 30 days prior to study entry
• Treatment with immune modulators or any investigational therapy within 30 days prior to study entry
• Evidence of HIV seroconversion within 6 months prior to study entry
• Illness requiring systemic treatment and/or hospitalization
• Substance abuse that, in the opinion of the investigator, would interfere with adherence to study requirements
• Requirement for any current medications that are prohibited with any study medication. More information on this criterion can be found in the protocol.
• Evidence of any major resistance-associated mutation on any genotype performed prior to study entry or at the time of screening. More information on this criterion can be found in the protocol.
• Abnormal laboratory values. More information on this criterion can be found in the protocol.
• Pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Oral RAL and FTC/TDF for 72 weeks	Drug: Raltegravir; 400 mg tablet taken orally twice daily; Other Names: RAL; Drug: Emtricitabine/tenofovir disoproxil fumarate; Fixed dose tablet containing 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate taken once daily. FTC/TDF will not be provided by the study and must be obtained by the particpant's health care provider.; Other Names: FTC/TDF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Viral load decay rates	Through Day 56

Secondary Outcome Measures

Outcome Measure	Time Frame
Viral load decay rates	From Weeks 24 to 72
Proportion of participants with a viral load less than 50 copies/ml	At Weeks 24, 48, and 72
Safety and tolerability. More information on this criterion can be found in the protocol.	Throughout study
CD4 and CD8 count	Throughout study
Resistance mutations to RAL, FTC, and TDF	Throughout study
Minimum concentration (Cmin) for RAL, FTC, and TDF	Throughout study
Changes in viral load	At Day 7
Self-reported adherence	Throughout study
Cell-associated proviral DNA, LTR circular DNA, and integrated proviral DNA	Throughout study
Viral load	From Week 24 to Week 72

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Adult AIDS Clinical Trials Group
• Investigators: Study Chair: Adriana Andrade, MD, MPH, Johns Hopkins University

Publications and helpful links

General Publications

• Evering TH, Markowitz M. Raltegravir: an integrase inhibitor for HIV-1. Expert Opin Investig Drugs. 2008 Mar;17(3):413-22. doi: 10.1517/13543784.17.3.413.
• Sedaghat AR, Dinoso JB, Shen L, Wilke CO, Siliciano RF. Decay dynamics of HIV-1 depend on the inhibited stages of the viral life cycle. Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4832-7. doi: 10.1073/pnas.0711372105. Epub 2008 Mar 24.
• Funderburg NT, Xu D, Playford MP, Joshi AA, Andrade A, Kuritzkes DR, Lederman MM, Mehta NN. Treatment of HIV infection with a raltegravir-based regimen increases LDL levels, but improves HDL cholesterol efflux capacity. Antivir Ther. 2017;22(1):71-75. doi: 10.3851/IMP3091. Epub 2016 Oct 14.
• Funderburg NT, Andrade A, Chan ES, Rosenkranz SL, Lu D, Clagett B, Pilch-Cooper HA, Rodriguez B, Feinberg J, Daar E, Mellors J, Kuritzkes D, Jacobson JM, Lederman MM. Dynamics of immune reconstitution and activation markers in HIV+ treatment-naive patients treated with raltegravir, tenofovir disoproxil fumarate and emtricitabine. PLoS One. 2013 Dec 18;8(12):e83514. doi: 10.1371/journal.pone.0083514. eCollection 2013.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: April 16, 2008
• First Submitted That Met QC Criteria: April 16, 2008
• First Posted (Estimate): April 18, 2008

Study Record Updates

• Last Update Posted (Actual): November 1, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Viral Load; Treatment Naive; HIV Integrase Inhibitors; HIV Nucleoside Reverse Transcriptase Inhibitors
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Tenofovir; Emtricitabine; Raltegravir Potassium; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: A5248; 10532 (DAIDS ES); ACTG A5248