title: Constant mean viral copy number per infected cell in tissues regardless of high, low, or undetectable plasma HIV RNA.
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 <2/10(6) 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.
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D001706:Biopsy; D002452:Cell Count; D015658:HIV Infections / Q000097:blood*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D008198:Lymph Nodes / Q000187:drug effects / Q000821:virology*; D009000:Monocytes; D012367:RNA, Viral / Q000032:analysis / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019562:Viral Load; D014766:Viremia / Q000235:genetics; D014779:Virus Replication / Q000235:genetics