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Randomized Controlled Trial
. 2012 Mar 1;59(3):229-35.
doi: 10.1097/QAI.0b013e31823fd1f2.

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

Rajesh T Gandhi  1 , 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; AIDS Clinical Trials Group (ACTG) A5244 Team
Collaborators, Affiliations
Randomized Controlled Trial

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

Rajesh T Gandhi et al. J Acquir Immune Defic Syndr. .

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.

Trial registration: ClinicalTrials.gov NCT00515827.

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Conflict of interest statement

Conflict of interest: RTG has received grant support from Tibotec and Gilead. DMM has served as a consultant and received grant support from Merck, Bristol-Myers Squibb, and Tibotec.

JWM is a consultant for Gilead Sciences, Merck, and RFS Pharma and owns share options in RFS Pharma. MML has served as a consultant to Merck. JJE has served as a consultant and received grant support from Merck and GlaxoSmithKline/Viiv and has served as a consultant for Bristol-Myers Squibb, Tibotec, Gilead and Tobira. RD has received grant support from Merck and Virco, and served as a consultant to Tibotec.

Figures

Figure 1
Figure 1. 2-LTR Circles During Raltegravir Intensification
2-LTR circles were measured at baseline, week 12 and 24 in patients who received raltegravir (RAL)-first or placebo-first; 12 weeks after initial treatment assignment, the two groups crossed-over to the other treatment (see Methods). BL: baseline.
Figure 2
Figure 2. Total Cellular HIV-1 DNA During Raltegravir Intensification
HIV-1 DNA was measured at baseline, week 12 and 24 in patients who received raltegravir (RAL)-first or placebo-first; 12 weeks after initial treatment assignment, the two groups crossed-over to the other treatment (see Methods). BL: baseline.
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