Effect of IL-2 on the pool of latently infected, resting CD4+ T cells in HIV-1

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Despite the success of HAART in driving plasma viremia to below the levels of detectability in a substantial proportion of HIV-infected individuals, the persistence of a latent reservoir of HIV in resting CD4+ T cells in HAART-treated individuals is considered to be a major impediment to the long-term control of HIV infection. In our attempts to diminish or eliminate latently infected, resting CD4+ T cells in infected individuals receiving HAART, we investigated a possible role of interleukin-2 in purging of latent HIV in resting CD4+ T cells in patients receiving IL-2 plus HAART. We conducted a non-randomized, cross-sectional analysis of this pool of latently infected, resting CD4+ T cells in HIV-1 infected patients receiving intermittent IL-2 plus continuous HAART compared to those receiving continuous HAART alone. The frequency of resting CD4+ T cells carrying replication- competent HIV in the blood of patients receiving IL-2 plus HAART was significantly lower than that of patients receiving HAART alone (p=0.01). Replication-competent HIV was not demonstrated by standard co-culture assays in 6 of 14 patients receiving IL-2 plus HAART, whereas all 12 patients receiving HAART alone carried infectious HIV in their resting CD4+ T cells. Of the 6 standard co-culture-negative patients receiving IL-2 plus HAART, virus could not be isolated from the peripheral blood CD4+ T cells in 3 patients despite the fact that large numbers of resting CD4+ T cells were cultured. Lymph node biopsies were then performed in 2 of these 3 patients and virus could not be isolated. These results suggest that the intermittent administration of IL-2 together with continuous HAART may lead to a substantial reduction in the pool of resting CD4+ T cells that harbor replication-competent HIV. - HIV; viral reservoir; latency; resting CD4+ T cells; highly active antiretroviral therapy; interleukin-2. - Human Subjects