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

HIV Infections Clinical Trial

— HIV  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00654147
• Other study ID #: A009
• Status: Completed
• Phase: Phase 2
• First received: April 2, 2008
• Last updated: July 11, 2015
• Start date: April 2008
• Est. completion date: January 2012

Study information

• Verified date: July 2015
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Raltegravir & Lopinavir/ritonavir
Two drug regimen of an integrase inhibitor and ritonavir boosted protease inhibitor
• Raltegravir and emtricitabine/tenofovir
Three drug regimen of an integrase inhibitor and a fixed dose combination of a non-nucleoside/nucleotide inhibitors

Locations

Country	Name	City	State
United States	University of Miami AIDS Clinical Research Unit	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Margaret A. Fischl, M.D.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Confirmed Virologic Failure	time to confirmed viologic failure at 24 weeks (up to 48 weeks)	weeks	No
Primary	Time to Virologic Failure	time to virologic failure at week 24 (up to 48 weeks)	week 24 (up to 48 weeks)	No
Secondary	Study Medication Toxicity-related Discontinuation .	grade 3 and grade 4 symptoms and laboratory study treatment limiting toxicity	48 weeks	No
Secondary	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	No
Secondary	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	No
Secondary	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	No