How does the timing of antiretroviral therapy initiation in acute infection affect HIV reservoirs?

Curr Opin HIV AIDS. 2015 Jan;10(1):18-28. doi: 10.1097/COH.0000000000000122.

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Disease
  • Anti-Retroviral Agents / administration & dosage*
  • Anti-Retroviral Agents / pharmacology
  • Disease Reservoirs / virology
  • Drug Administration Schedule
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1*
  • Humans
  • Viral Load / drug effects

Substances

  • Anti-Retroviral Agents