Dynamics of Provirus Load and Lymphocyte Subsets after Interleukin 2 Treatment in HIV-Infected Patients

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Abstract
The association of antiretroviral agents plus interleukin 2 (IL-2) represents an efficient approach to the treatment of HIV+ subjects. While the effects of IL-2 on the immune system have been investigated, little is known concerning its impact on HIV dynamics. Two antiretroviral drugs control HIV viremia, but have minimal effects on the proviral load, a predictor of disease progression and response to therapy. The aim of this study was to define the effect of rIL-2 on HIV proviral copy numbers and its relationship to changes in CD4+ and CD8+ subsets. Twelve HIV+ patients with CD4 cell counts between 200 and 500 cells/mm3 were treated with six cycles of subcutaneous rIL-2, in combination with zidovudine and didanosine. This regimen resulted in a rapid and durable decrease in proviral load in the peripheral blood, in an increase in CD8+ lymphocytes, and in the emergence of a CD4+ CD45RA+ T subset. These results demonstrate that the rationale for IL-2 administration to HIV+ patients may depend not only on its effects on the immune system, but also on the reduction of the number of infected cells, reinforcing the notion that IL-2 can have a favorable impact on the natural history of HIV infection.