www.hivandhepatitis.com

Immediate Antiretroviral Therapy Reduces HIV Infection of Resting CD4 T-Cells

Starting antiretroviral therapy (ART) during the acute phase of HIV infection appears to reduce the number of latently infected resting CD4 T-cells in most people, but this may not be the case for individuals with very few initially infected cells, according to a study published in the May 29, 2012, advance online edition of Proceedings of the National Academy of Sciences.

One of the reasons HIV is so difficult to eradicate is that it can insert its genetic material into resting T-cells. As long as these cells remain quiescent, this persistent virus is "silenced." This reservoir of latent HIV is not vulnerable to antiretroviral drugs, which only work when the virus is replicating. If the cells become activated, however, the viral DNA they contain can begin producing new infectious virus particles. A better understanding of viral latency can provide clues to help develop a cure.

Nancie Archin and David Margolis from the University of North Carolina at Chapel Hill and colleaguesexplored the viral kinetics of resting cell infection using a mathematical model that predicts the initial frequency of infected resting cells measured about 1 year after infection, based on the time of ART initiation and dynamic changes in HIV viral load and CD4 cell count.

Results

• The model indicated that in a majority patients who start treatment during acute HIV infection -- while still seronegative -- early ART would reduce the generation of latently infected cells.
• In this group, restingcell infection usually declines after the first year on ART.
• When resting cell infection had a frequency of less than 0.5 per million, however, the model showed a "striking absence" of decline in infected cell numbers.
• Here, low-level viremia was observed more frequently as resting cell infection increased.

These findings, the study authors wrote, "suggest that...the degree of resting cell infection is directly related to the availability of CD4+ T-cells susceptible to HIV, regardless of whether virus levels are controlled by the immune response or antiretroviral drugs.

They also surmised that "2 pools of infected resting CD4+ T-cells exist, namely, less stable cells, observable in patients in whom viremia is not well controlled in early infection, and extremely stable cells that are established despite early ART."

These results, they concluded, "reinforce and extend the concept that new approaches will be needed to eradicate HIV infection, and, in particular, highlight the need to target the extremely small but universal, long-lived latent reservoir."

6/12/12

Reference

NM Archin, NK Vaidya, JD Kuruc, et al. Immediateantiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection. Proceedings of the National Academy of Sciences USA. May 29, 2012 (Epub ahead of print).