PLoS Pathogens (Jan 2013)

Prospective antiretroviral treatment of asymptomatic, HIV-1 infected controllers.

  • Hiroyu Hatano,
  • Steven A Yukl,
  • April L Ferre,
  • Erin H Graf,
  • Ma Somsouk,
  • Elizabeth Sinclair,
  • Mohamed Abdel-Mohsen,
  • Teri Liegler,
  • Kara Harvill,
  • Rebecca Hoh,
  • Sarah Palmer,
  • Peter Bacchetti,
  • Peter W Hunt,
  • Jeffrey N Martin,
  • Joseph M McCune,
  • Russell P Tracy,
  • Michael P Busch,
  • Una O'Doherty,
  • Barbara L Shacklett,
  • Joseph K Wong,
  • Steven G Deeks

DOI
https://doi.org/10.1371/journal.ppat.1003691
Journal volume & issue
Vol. 9, no. 10
p. e1003691

Abstract

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The study of HIV-infected "controllers" who are able to maintain low levels of plasma HIV RNA in the absence of antiretroviral therapy (ART) may provide insights for HIV cure and vaccine strategies. Despite maintaining very low levels of plasma viremia, controllers have elevated immune activation and accelerated atherosclerosis. However, the degree to which low-level replication contributes to these phenomena is not known. Sixteen asymptomatic controllers were prospectively treated with ART for 24 weeks. Controllers had a statistically significant decrease in ultrasensitive plasma and rectal HIV RNA levels with ART. Markers of T cell activation/dysfunction in blood and gut mucosa also decreased substantially with ART. Similar reductions were observed in the subset of "elite" controllers with pre-ART plasma HIV RNA levels below conventional assays (<40 copies/mL). These data confirm that HIV replication persists in controllers and contributes to a chronic inflammatory state. ART should be considered for these individuals (ClinicalTrials.gov NCT01025427).