Clinical trial NCT00654147: Raltegravir + Lopinavir/Ritonavir or Emtricitabine/Tenofovir for HIV Treatment Naive Subjects
Official title: A Pilot Study to Assess Virologic Suppression and Immune Recovery With Raltegravir and Lopinavir/Ritonavir and Raltegravir and Emtricitabine/Tenofovir in HIV-1 Infected Treatment-naïve Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: HIV
antiretroviral therapy naive
Integrase inhibitor
HIV/AIDS
treatment naïve
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2008-04-07
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A prospective, randomized, open-label pilot study to assess virologic suppression and immunologic recovery associated with a two-drug antiretroviral regimen of Raltegravir and the protease inhibitor lopinavir/ritonavir (LPV/r) and a three drug regimen with Raltegravir and two nRTIs (emtricitabine/tenofovir) in HIV-1 infected treatment-naïve subjects.

Immunology Substudy added to determine the kinetics of recovery of CD4 T cells and subpopulations (regulatory T cell \[T regs\], TH-17 and TH1) after treatment initiation with Raltegravir based regimens and their relationship with functional CD8 T cells and if Raltegravir containing therapies leads to decreases in markers of gut microbial translocation and of cellular and soluble markers of immune activation.

Detailed description: A009 is a prospective, randomized, open-label pilot study to assess virologic suppression and immune recovery rates associated with a two-drug potent antiretroviral regimen of raltegravir and the protease inhibitor lopinavir/ritonavir and a three-drug regimen with raltegravir and two nRTIs (emtricitabine/tenofovir) in treatment-naïve subjects.

HIV-1-infected subjects who are antiretroviral drug-naïve and have plasma HIV-1 RNA levels ≥5000 copies/ml obtained within 30 days prior to study entry will be randomized 1:1 to Raltegravir 400 mg BID + LPV 400 mg/RTV 100 mg BID (Arm A) or Raltegravir 400 mg BID + FTC 200 mg/TDF 300 mg QD (Arm B).

Subjects will have measurements of HIV-1 RNA and CD4+ and CD8+ T-cell counts at pre-entry and entry. The average of these measurements will be used to establish their baseline values. Following entry, subjects will have plasma HIV-1 RNA samples drawn at days 2, 4, 8 and at weeks 2, 4, 8, 16, 24, 32, 40 and 48 and at virologic failure. CD38 expression on CD4+/CD8+ cells and CD38/HLA-DR activation antigen on CD4+ and CD8+ cells and subsets T-cell percentage will be done at entry, day 8 and weeks 4, 8, 24 and at virologic failure by advanced flow cytometry.

Eligibility criteria: Inclusion Criteria:

* Documented HIV Infection
* Genotypic resistance without major resistance mutations within 30 days
* Antiretroviral drug-naïve
* Screening HIV-1 RNA ≥5000
* Women of reproductive potential
* Negative pregnancy test within 48 hours

Exclusion Criteria:

* Acute or recent HIV-1 infection
* Currently breast feeding
* Use of immunomodulators
* Evidence of major resistance mutations
* HBsAg positive
* Acute hepatitis of any etiology or clinically significant liver disease
* Current imprisonment or involuntary incarceration

Primary outcomes:
measure: Time to Confirmed Virologic Failure
timeFrame: weeks
measure: Time to Virologic Failure
timeFrame: week 24 (up to 48 weeks)
Secondary outcomes:
measure: Study Medication Toxicity-related Discontinuation .
timeFrame: 48 weeks
measure: Weeks to HIV-1 RNA <200 Copies/ml
timeFrame: from date of treatment start to first week documented viral suppression
measure: Change From Baseline CD4+ and CD8+ Cell Counts
timeFrame: Baseline, Weeks 16 and 24
measure: Study Medication Tolerability
timeFrame: date started study treatment to first week documented change study treatment up to week 48
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami AIDS Clinical Research Unit
state: Florida
Study officials:
affiliation: University of Miami AIDS Clinical Research Unit
name: Margaret A Fischl, M.D.
role: STUDY_CHAIR
References: