HIV type 1 (HIV-1) proviral reservoirs decay continuously under sustained virologic control in HIV-1-infected children who received early treatment

J Infect Dis. 2014 Nov 15;210(10):1529-38. doi: 10.1093/infdis/jiu297. Epub 2014 May 21.

Abstract

Background: Early initiation of combination antiretroviral therapy (cART) to human immunodeficiency virus type 1 (HIV-1)-infected infants controls HIV-1 replication and reduces mortality.

Methods: Plasma viremia (lower limit of detection, <2 copies/mL), T-cell activation, HIV-1-specific immune responses, and the persistence of cells carrying replication-competent virus were quantified during long-term effective combination antiretroviral therapy (cART) in 4 perinatally HIV-1-infected youth who received treatment early (the ET group) and 4 who received treatment late (the LT group). Decay in peripheral blood mononuclear cell (PBMC) proviral DNA levels was also measured over time in the ET youth.

Results: Plasma viremia was not detected in any ET youth but was detected in all LT youth (median, 8 copies/mL; P = .03). PBMC proviral load was significantly lower in ET youth (median, 7 copies per million PBMCs) than in LT youth (median, 181 copies; P = .03). Replication-competent virus was recovered from all LT youth but only 1 ET youth. Decay in proviral DNA was noted in all 4 ET youth in association with limited T-cell activation and with absent to minimal HIV-1-specific immune responses.

Conclusions: Initiation of early effective cART during infancy significantly limits circulating levels of proviral and replication-competent HIV-1 and promotes continuous decay of viral reservoirs. Continued cART with reduction in HIV-1 reservoirs over time may facilitate HIV-1 eradication strategies.

Keywords: continuous HIV-1 decay; early antiretroviral therapy; prolonged viral suppression; proviral reservoirs; reduced HIV reservoirs.

Publication types

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

MeSH terms

  • Adolescent
  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1 / isolation & purification*
  • Humans
  • Infant
  • Infant, Newborn
  • Leukocytes, Mononuclear / virology
  • Male
  • Proviruses / isolation & purification*
  • Secondary Prevention*
  • Treatment Outcome
  • Viral Load*

Substances

  • Anti-Retroviral Agents