In a double blind trial published this week in PLoS Medicine Rajesh Gandhi and colleagues detect no significant reduction in viral load after people with low-level HIV viremia had an integrase inhibitor added to their treatment regimen.
Antiretroviral therapy (ART) consists of combinations of drugs that prevent viral replication by inhibiting essential viral enzymes such as reverse transcriptase and protease. However, despite ART, residual viremia (virus in the blood) still occurs in HIV-positive individuals. The origin of this low-level residual viremia, and whether intensification of treatment can affect it, is controversial.
In this randomized, controlled trial the researchers assessed whether the addition of raltegravir (a drug that inhibits HIV integrase) to standard ART had any effect on residual viremia. The researchers found that the addition of raltegravir to ART for 12 weeks did not demonstrably reduce low-level residual viremia in HIV-positive individuals receiving standard ART. These findings suggest that residual viremia might be due to the release of HIV from stable reservoirs. If so, new therapeutic strategies designed to eliminate these reservoirs of latently infected cells will be required to cure HIV infection.
Funding: The project was supported by Award Number U01AI068636 from the National Institute of Allergy and Infectious Diseases. The project was also supported by a grant from the National Institute of Allergy and Infectious Diseases to the Statistical and Data Analysis Center (AI068634). In addition, J W M was supported by the following National Institutes of Health grants: 5U01A1068636-04 and NIH25XS119. J M C was a research professor of the American Cancer Society, with support from the F. M. Kirby Foundation. The content is solely the responsibility of the authors and does not represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. The study was also supported by a research grant from the Investigator- Initiated Studies Program of Merck Sharp & Dohme, Corp. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme, Corp.
Competing Interests: WM: Gilead Sciences (consultant); Merck (consultant and grant support); Chimerix (consultant); RFS Pharmaceuticals (owns stock options). JJE: Merck, GlaxoSmithKline (consultant and grant support), Bristol-Myers Squibb, Tibotec, Chimerix, Avexa, and Tobira (consultant). RTG: Tibotec (research grant support) and Gilead (grant support). DM: Merck, Bristol-Myers Squibb, and GlaxoSmithKline (consultant and research support); Gilead Sciences (research support and common stock); Chimerix (consultant); Roche, Trimeris, and Tibotec (research support).
Citation: Gandhi RT, Zheng L, Bosch RJ, Chan ES, Margolis DM, et al. (2010) The Effect of Raltegravir Intensification on Low-level Residual Viremiain HIV-Infected Patients on Antiretroviral Therapy: A Randomized Controlled Trial. PLoS Med 7 (8): e1000321. doi:10.1371/journal.pmed.1000321
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CONTACT:
Rajesh Gandhi
Massachusetts General Hospital (and Harvard Medical School)
Infectious Diseases
Boston
United States of America
617-724-9690
RGANDHI@PARTNERS.ORG
Journal
PLoS Medicine