Raltegravir + Lopinavir/Ritonavir or Emtricitabine/Tenofovir for HIV Treatment Naive Subjects

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Raltegravir & Lopinavir/ritonavir
* Drug: Raltegravir and emtricitabine/tenofovir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Raltegravir & Lopinavir/ritonavir<br>Raltegravir 400 mg tablet and Lopinavir/ritonavir capsule by mouth, every 12 hours for 48 weeks | Drug: Raltegravir & Lopinavir/ritonavir<br>* Two drug regimen of an integrase inhibitor and ritonavir boosted protease inhibitor<br>* Other names: Kaletra;|
| Active Comparator: Raltegravir & emtricitabine/tenofovir<br>Raltegravir 400 mg tablet bu mouth, every 12 hours for 48 weeks and tenofovir/embritcitabine 200 mg/100 mg table by mouth, once daily for 48 weeks | Drug: Raltegravir and emtricitabine/tenofovir<br>* Three drug regimen of an integrase inhibitor and a fixed dose combination of a non-nucleoside/nucleotide inhibitors<br>* Other names: Truvada;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Confirmed Virologic Failure | time to confirmed viologic failure at 24 weeks (up to 48 weeks) | weeks | 
| Time to Virologic Failure | time to virologic failure at week 24 (up to 48 weeks) | week 24 (up to 48 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study Medication Toxicity-related Discontinuation . | grade 3 and grade 4 symptoms and laboratory study treatment limiting toxicity | 48 weeks | 
| Weeks to HIV-1 RNA <200 Copies/ml | time to viral suppression noted as week on study treatment to attain HIV-1 RNA < 200 copies/ml | from date of treatment start to first week documented viral suppression | 
| Change From Baseline CD4+ and CD8+ Cell Counts | mean change in CD4+ and CD8+ T-lymphocytes counts from baseline (defined as the average of pre-entry and entry values) at weeks 16 and 24 in the two treatment arms | Baseline, Weeks 16 and 24 | 
| Study Medication Tolerability | study treatment tolerability as measured by number of subjects receiving study treatment who either discontinued or changed any component of study treatment | date started study treatment to first week documented change study treatment up to week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, antiretroviral therapy naive, Integrase inhibitor, HIV/AIDS, treatment naïve