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

Quantitative analysis of the relationship between virus expression and dise ase outcome has been critical for understanding HIV-1 pathogenesis. Yet the amount of viral RNA contained within an HIV-expressing cell and the relati onship between the number of virus-producing cells and plasma virus load ha s not been established or reflected in models of viral dynamics. We report here a novel strategy for the coordinated analysis of virus expression in l ymph node specimens. The results obtained for patients with a broad range o f plasma viral loads before and after antiretroviral therapy reveal a const ant mean viral (v)RNA copy number (3.6 log(10) copies) per infected cell, r egardless of plasma virus load or treatment status. In addition, there was a significant but nonlinear direct correlation between the frequency of vRN A(+) lymph node cells and plasma vRNA. As predicted From this relationship, residual cells expressing this same mean copy number are detectable (frequ ency <2/10(6) cells) in tissues of treated patients who have plasma vRNA le vels below the current detectable threshold (<50 copies/ml). These data sug gest that fully replication-active cells are responsible for sustaining vir emia after initiation of potent antiretroviral therapy and that plasma viru s titers con-elate, albeit in a nonlinear fashion, with the number of virus -expressing cells in lymphoid tissue.