No effect of raltegravir intensification on viral replication markers in the blood of HIV-1-infected patients receiving antiretroviral therapy

Rajesh T. Gandhi*, Robert W. Coombs, Ellen S. Chan, Ronald J. Bosch, Lu Zheng, David M. Margolis, Sarah Read, Beatrice Kallungal, Ming Chang, Erin A. Goecker, Ann Wiegand, Mary Kearney, Jeffrey M. Jacobson, Richard D'Aquila, Michael M. Lederman, John W. Mellors, Joseph J. Eron

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

Background: Controversy continues regarding the extent of ongoing viral replication in HIV-1-infected patients on effective antiretroviral therapy (ART). Adding an additional potent agent, such as raltegravir, to effective ART in patients with low-level residual viremia may reveal whether there is ongoing HIV-1 replication. Methods: We previously reported the outcome of a randomized placebo-controlled study of raltegravir intensification in patients on ART with HIV-1 RNA <50 copies per milliliter that showed no effect on residual viremia measured by single copy assay. We now report the effects of raltegravir intensification in that trial on other potential measures of ongoing HIV-1 replication as follows: 2-LTR HIV-1 circles, total cellular HIV-1 DNA, and T-cell activation. Results: Of 50 patients tested, 12 (24%) had 2-LTR circles detected at baseline. Patients who were 2-LTR-positive had higher plasma HIV-1 RNA and HIV-1 DNA levels than 2-LTR-negative individuals. At week 12 of raltegravir intensification, there was no change from baseline in 2-LTR circles, in total HIV-1 DNA or in the ratio of 2-LTR circles to total HIV-1 DNA. There was also no change in markers of T-cell activation. Conclusions: In HIV-1-infected individuals on effective ART, we find no evidence of ongoing viral replication in the blood that is suppressible by raltegravir intensification. The results imply that raltegravir intensification alone will not eradicate HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)229-235
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Volume59
Issue number3
DOIs
StatePublished - Mar 1 2012

Keywords

  • 2-LTR circles
  • HIV-1
  • HIV-1 DNA
  • Raltegravir
  • Reservoirs
  • T-cell activation
  • Viral replication

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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