Antiretroviral Intensification and the HIV Latent Reservoir

Rajesh T. Gandhi, MD

In a small study of HIV-infected patients on standard antiretroviral therapy, adding maraviroc or raltegravir led to a reduction in the latent reservoir.

Despite the ability of combination antiretroviral therapy (ART) to reduce HIV RNA to extremely low levels in the blood, the virus persists in long-lived reservoirs found in resting memory CD4 cells — the latent reservoir — and tissues. In recent years, various intensification trials — in which other agents have been added to standard ART regimens — have failed to demonstrate a reduction in plasma HIV RNA levels (measured using sensitive research assays). Now, researchers in Spain have examined the effect of antiretroviral intensification on HIV in resting CD4 cells.

Fifteen patients on standard ART with undetectable plasma HIV RNA (as measured by commercial assays) received maraviroc (n=7) or raltegravir (n=8) intensification for 48 weeks; the intensifying agent was then withdrawn, and the participants were followed for an additional 24 weeks. The HIV reservoir in blood was quantified using a co-culture assay as infectious units per million (IUPM) resting CD4 cells.

Before the intensifying agent was added, the median IUPM was 1.1. After 48 weeks of intensification, it declined to 0. Even 24 weeks after the additional agent was withdrawn, the IUPM level (median, 0) remained lower than prior to intensification.

Citation(s):

Gutiérrez C et al. Dynamics of the HIV-1 latent reservoir after discontinuation of the intensification of antiretroviral treatment: Results of two clinical trials. AIDS 2013 Aug 24; 27:2081.