Changes in HIV reservoirs during long-term antiretroviral therapy.

Abstract

To review current knowledge about the impact of long-term combination antiretroviral therapy (cART) on HIV reservoirs. The number of HIV-infected cells that persist during long-term antiretroviral therapy is associated with the stage of HIV infection at the time of treatment initiation. Initiation of cART reduces the number of infected cells over the first 4 years of therapy, but thereafter there is no further decline despite long-term effective cART. The remarkable stability of infected cell numbers is likely due to a balance among homeostatic or antigen-driven proliferation of infected memory T-cells subsets, clonal expansion of a subset of infected cells as a consequence of specific retroviral integration sites, and death of other infected cells. At present, there is no effective means of accelerating the decay of infected cells in individuals initiated on cART during chronic HIV infection. Given the stability and difficulty in eliminating HIV-infected cells, early initiation of cART in treatment-naïve HIV-infected patients is currently the most effective way to limit the size and diversity of HIV reservoirs.