The long-lived viral reservoir is a major obstacle to achieving a cure for HIV. Therapeutic strategies, such as early antiretroviral therapy (ART), may be a prerequisite to achieving long-term control of viral replication upon ART withdrawal.
HIV persistence is established early in acute HIV infection (AHI) with infection in long-lived memory CD4+ T cells. Studies conducted in nonhuman primates have suggested that this could occur as early as 3 days postinfection; however, the timing in humans is uncertain. ART during AHI significantly restricts the HIV reservoirs as compared with later treatment. Early ART, particularly prior to the detection of HIV immunoglobulin M, may also reduce the contribution of the long-lived central memory CD4+ T cells to the total HIV reservoir, a profile observed in individuals who naturally control HIV without ART.
It is clear that early ART has a greater impact in limiting the HIV reservoirs than later treatment. However, latently infected long-lived memory CD4+ T cells persist in most early treated individuals. Therefore, additional interventions will likely be required to eliminate all cells capable of producing replication-competent virus but treatment in AHI may be the critical first step in containing the HIV reservoirs.
aU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring
bHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland
cThe University of North Carolina, Chapel Hill, North Carolina
dVaccine and Gene Therapy Institute Florida, Port St Lucie, Florida, USA
Correspondence to Jintanat Ananworanich, MD, PhD, U.S. Military HIV Research Program, 6720A Rockledge Drive, Suite 400, Bethesda, MD 20817, USA. Tel: +1 301 500 3949; fax: +1 301 500 3666; e-mail: Jananworanich@hivresearch.org