Constant mean viral copy number per infected cell in tissues regardless of high, low, or undetectable plasma HIV RNA

Academic Article

Abstract

  • Quantitative analysis of the relationship between virus expression and disease outcome has been critical for understanding HIV-1 pathogenesis. Yet the amount of viral RNA contained within an HIV-expressing cell and the relationship between the number of virus-producing cells and plasma virus load has not been established or reflected in models of viral dynamics. We report here a novel strategy for the coordinated analysis of virus expression in lymph node specimens. The results obtained for patients with a broad range of plasma viral loads before and after antiretroviral therapy reveal a constant mean viral (v)RNA copy number (3.6 log10 copies) per infected cell, regardless of plasma virus load or treatment status. In addition, there was a significant but nonlinear direct correlation between the frequency of vRNA+ lymph node cells and plasma vRNA. As predicted from this relationship, residual cells expressing this same mean copy number are detectable (frequency <2/106 cells) in tissues of treated patients who have plasma vRNA levels below the current detectable threshold (<50 copies/ml). These data suggest that fully replication-active cells are responsible for sustaining viremia after initiation of potent antiretroviral therapy and that plasma virus titers correlate, albeit in a nonlinear fashion, with the number of virus-expressing cells in lymphoid tissue.
  • Digital Object Identifier (doi)

    Author List

  • Hockett RD; Kilby JM; Derdeyn CA; Saag MS; Sillers M; Squires K; Chiz S; Nowak MA; Shaw GM; Bucy RP
  • Start Page

  • 1545
  • End Page

  • 1554
  • Volume

  • 189
  • Issue

  • 10