Study of the Antiviral and Immunological Effects of Intensification of Suppressive Antiretroviral Therapy With Maraviroc

HIV Infections Clinical Trial

Official title: A Two-Arm, Single Site, Proof of Concept Study of the Antiviral and Immunological Effects of Intensification of Suppressive Antiretroviral Therapy With Maraviroc, a CCR5 Antagonist (ADARC 2007-02)

Status Completed

Clinical Trial Summary

Hypothesis: Intensification of current ARV regimens with maraviroc will result in more complete suppression of viral replication, particularly in the gastrointestinal mucosa with resultant reduction in markers of immune activation and improved GI immune reconstitution.

Clinical Trial Description

• DURATION: Subjects will participate for a minimum of 28 weeks.

• SAMPLE SIZE: 18 subjects randomized 2:1 continued ARVs plus maraviroc versus continued ARVs plus additional ARV to be determined based on baseline ARV regimen.

• REGIMEN: At entry, subjects will be randomized to one of the following in a 2:1 ratio:

ARM A:

Intensification with maraviroc for 24 weeks at one of the following doses:

• 150 mg orally BID when coadministered with a ritonavir-boosted protease inhibitor

• 600 mg orally BID when coadministered with efavirenz or nevirapine

ARM B

Intensification with an additional NRTI for 12 weeks then cross over to maraviroc intensification for an additional 12 weeks as above:

• Addition of abacavir 600 mg orally once daily to a tenofovir containing regimen for 12 weeks then replacing the abacavir with maraviroc

• Addition of an alternate FDA approved NRTI [such as zidovudine (AZT) or didanosine (ddi)] at standard oral dosing to a tenofovir containing regimen for 12 weeks (if the participant declines abacavir therapy) then replacing the alternate NRTI with maraviroc.

The objectives of this study are:

To determine whether intensification of current ARV regimens with maraviroc will result in more complete suppression of viral replication and improved immune reconstitution in GI mucosal lymphoid compartment based on:

• Reduction in normalized levels of CD4+MMC HIV-1 RNA as determined by PCR pre- and post- intensification at week 12 in Arm A versus Arm B.

• Reduction in normalized levels of CD4+ mucosal mononuclear cell (MMC) HIV-1 RNA at week 12 compared to baseline in Arm A.

• Reduction in %CD4+MMC HIV-1 RNA positive as determined by PCR pre- and post- intensification between Arm A and Arm B as well as week 12 and 24 post maraviroc intensification.

• Levels of CD4+ T cells in GALT (% by flow and absolute #s by immunohistochemistry).

• Phenotype of cells in GALT by flow (memory, naive, R5, X4, dual expressing).

• Levels of activation of CD4 and CD8 in PB and GALT using HLA DR and CD 38. ;

Study Design

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

Related Conditions & MeSH terms

• HIV Infections

• NCT number: NCT00703586
• Study type: Interventional
• Source: Rockefeller University
• Status: Completed
• Phase: Phase 1
• Start date: September 2007
• Completion date: May 2011