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Intensification of Antiretroviral Therapy with a CCR5 Antagonist in Patients with Chronic HIV-1 Infection: Effect on T Cells Latently Infected
Published: Thursday, December 08, 2011
Author: Carolina Gutiérrez et al.

by Carolina Gutiérrez, Laura Díaz, Alejandro Vallejo, Beatriz Hernández-Novoa, María Abad, Nadia Madrid, Viktor Dahl, Rafael Rubio, Ana M. Moreno, Fernando Dronda, José Luis Casado, Enrique Navas, María Jesús Pérez-Elías, Javier Zamora, Sarah Palmer, Eduardo Muñoz, María Ángeles Muñoz-Fernández, Santiago Moreno

Objective

The primary objective was to assess the effect of MVC intensification on latently infected CD4+ T cells in chronically HIV-1-infected patients receiving antiretroviral therapy.

Methods

We performed an open-label pilot phase II clinical trial involving chronically HIV-1-infected patients receiving stable antiretroviral therapy whose regimen was intensified with 48 weeks of maraviroc therapy. We analyzed the latent reservoir, the residual viremia and episomal 2LTR DNA to examine the relationship between these measures and the HIV-1 latent reservoir, immune activation, lymphocyte subsets (including effector and central memory T cells), and markers associated with bacterial translocation.

Results

Overall a non significant reduction in the size of the latent reservoir was found (p?=?0.068). A mean reduction of 1.82 IUPM was observed in 4 patients with detectable latent reservoir at baseline after 48 weeks of intensification. No effect on plasma residual viremia was observed. Unexpectedly, all the patients had detectable 2LTR DNA circles at week 24, while none of them showed those circles at the end of the study. No changes were detected in CD4+ or CD8+ counts, although a significant decrease was found in the proportion of HLA-DR+/CD38+ CD4+ and CD8+ T-cells. LPS and sCD14 levels increased.

Conclusions

Intensification with MVC was associated with a trend to a decrease in the size of the latent HIV-1 reservoir in memory T cells. No impact on residual viremia was detected. Additional studies with larger samples are needed to confirm the results.

Trial Registration

ClinicalTrials.gov NCT00795444

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