Clinical trial NCT00660972: Study of Viral Load Decay Rates in HIV Infected Participants Starting Treatment With Raltegravir (RAL) and Emtricitabine/Tenofovir Disoproxil Fumarate (TDF)
Official title: First-Phase Viral Decay Rates in Treatment-Naive Subjects Initiating Treatment With Raltegravir (RAL) and Emtricitabine (FTC)/Tenofovir Disoproxil Fumarate (TDF): A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: HIV Integrase Inhibitors
HIV Nucleoside Reverse Transcriptase Inhibitors
Treatment Naive
Viral Load
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Adult AIDS Clinical Trials Group
First posted: 2008-04-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Viral load decay rates
timeFrame: Through Day 56
Secondary outcomes:
measure: Viral load decay rates
timeFrame: From Weeks 24 to 72
measure: Proportion of participants with a viral load less than 50 copies/ml
timeFrame: At Weeks 24, 48, and 72
measure: Safety and tolerability. More information on this criterion can be found in the protocol.
timeFrame: Throughout study
measure: CD4 and CD8 count
timeFrame: Throughout study
measure: Resistance mutations to RAL, FTC, and TDF
timeFrame: Throughout study
measure: Minimum concentration (Cmin) for RAL, FTC, and TDF
timeFrame: Throughout study
measure: Changes in viral load
timeFrame: At Day 7
measure: Self-reported adherence
timeFrame: Throughout study
measure: Cell-associated proviral DNA, LTR circular DNA, and integrated proviral DNA
timeFrame: Throughout study
measure: Viral load
timeFrame: From Week 24 to Week 72
Other outcomes:
Locations:
city: San Diego
country: United States
facility: UCSD Antiviral Research Center CRS
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Baltimore
country: United States
facility: IHV Baltimore Treatment CRS
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University CRS
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University Therapeutics (WT) CRS
state: Missouri
city: New York
country: United States
facility: Harlem ACTG CRS
state: New York
city: Rochester
country: United States
facility: Trillium Health ACTG CRS
state: New York
city: Rochester
country: United States
facility: Univ. of Rochester ACTG CRS
state: New York
city: Cleveland
country: United States
facility: MetroHealth CRS
state: Ohio
city: Columbus
country: United States
facility: Ohio State University CRS
state: Ohio
city: Providence
country: United States
facility: The Miriam Hospital Clinical Research Site (TMH CRS) CRS
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt Therapeutics (VT) CRS
state: Tennessee
city: Houston
country: United States
facility: Houston AIDS Research Team CRS
state: Texas
Study officials:
affiliation: Johns Hopkins University
name: Adriana Andrade, MD, MPH
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.