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J. Exp. Med.,
Volume 189, Number 10, May 17, 1999 1545-1554
By
From the * Department of Pathology, the 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.
Department of Medicine, the § Department of Surgery, and
the Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham,
Alabama 35233-7331; and the ¶ Institute for Advanced Study, Princeton, New Jersey 08540
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