Interleukin-7 promotes HIV persistence during antiretroviral therapy
Claire Vandergeeten, Rémi Fromentin, Sandrina DaFonseca, Mariam B Lawani, Irini Sereti, Michael M Lederman, Moti Ramgopal, Jean-Pierre Routy, Rafick-Pierre Sékaly, Nicolas Chomont, Claire Vandergeeten, Rémi Fromentin, Sandrina DaFonseca, Mariam B Lawani, Irini Sereti, Michael M Lederman, Moti Ramgopal, Jean-Pierre Routy, Rafick-Pierre Sékaly, Nicolas Chomont
Abstract
HIV persists in latently infected memory CD4(+) T cells during antiretroviral therapy (ART). When administered to HIV-infected subjects receiving suppressive ART, interleukin-7 (IL-7) increases the number of CD4(+) T cells by promoting their survival and proliferation. However, little is known about the impact of IL-7 on HIV persistence during ART. By isolating large numbers of CD4(+) T cells from HIV-infected subjects, we demonstrate that IL-7 enhances viral production in productively infected cells but does not disrupt viral latency in latently infected cells. When administered to virally suppressed subjects, IL-7 led to the rapid proliferation of memory CD4(+) T cells, which resulted in a 70% increase in the absolute number of circulating CD4(+) T cells harboring integrated HIV DNA 4 weeks after therapy. The genetic diversity of the viral reservoir increased transiently in the majority of the subjects studied before returning to baseline values. Altogether, our results indicate that IL-7 promotes the mechanisms of HIV persistence during ART by enhancing residual levels of viral production and inducing proliferation of latently infected cells, and suggest that IL-7 does not represent a suitable candidate therapeutic strategy for HIV eradication. This trial was registered at www.clinicaltrials.gov as #NCT00099671 (AIDS Clinical Trials Group protocol 5214).
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Source: PubMed