HIV-Infected Individuals Receiving Effective Antiviral Therapy for Extended Periods of Time Continually Replenish Their Viral Reservoir

Purpose of the Study. Latently infected, resting CD4+ T cells provide a reservoir for HIV, and the persistence of these cells prevents the eradication of HIV even in patients who have received highly active antiretroviral therapy (HAART) for prolonged periods. The purpose of this study was to examine the underlying mechanisms by which HIV persists in CD4+ T cells in individuals treated effectively for up to 9 years. Methods. Eleven HIV-infected subjects were studied. These individuals had received effective therapy for an average of 8 years (range: 7.16–9.1 years). None of the patients had experienced detectable plasma viremia after initial suppression. Peripheral blood cells were obtained sequentially on all individuals and studied for the presence of replication-competent virus. Results. All infected subjects carried replication-competent HIV in their CD4+ T cells despite having received prolonged, effectively suppressive antiviral therapy. Contrary to current thinking, substantial higher levels of HIV proviral DNA were found in circulating activated CD4+ T cells when compared with the resting subset. Sequence analysis revealed evidence for cross infection between the resting and activated T-cell compartments, indicating that ongoing reactivation of latently infected, resting CD4+ T cells may occur in these patients. Conclusions. Continual replenishment of the CD4+ T-cell reservoir occurs despite prolonged periods of plasma aviremia. Reviewer Comments. It is only with the elimination of viral reservoirs that HIV infection can be “cured.” Resting T cells harboring proviral DNA do not live forever. However, the rate of viral replenishment in this cell compartment at least equals the natural decline in their numbers. Eliminating this cell reservoir will be a daunting task.