LEVELS OF HIV-INFECTED PERIPHERAL-BLOOD CELLS REMAIN STABLE THROUGHOUT THE NATURAL-HISTORY OF HIV-1 INFECTION

Objective: To clarify the relationship between the number of provirus- bearing peripheral blood mononuclear cells (PBMC) and HIV-1 disease pr ogression during the natural history of infection. Design: Twenty-four HIV-1-infected subjects with known seroconversion dates and long-term follow-up were retrospectively identified using the Swiss HIV Cohort Database. PBMC specimens from this cohort were retrieved from storage for analysis. Methods: Infected PBMC equivalents were determined by HI V-1 DNA quantitative competitive (QC)-PCR. The results were analysed w ith respect to HIV-1 disease stage and compared with a mathematical mo del of long-term HIV-1 disease progression. Results: PBMC HIV-1 DNA di d not correlate with major indices of disease progression, including t ime following primary infection, time before reaching a CD4 cell count less than 200 x 10(6)/l, and time before death. The number of PBMC ha rbouring HIV-1 provirus was relatively constant throughout the clinica l stages of HIV-1 infection, consistent with simulated data from a mat hematical model of long-term HIV-1 infection. We also showed that a bi ased interpretation of the QC-PCR data may arise when the values are e xpressed as HIV-1 DNA copies per PBMC or per CD4 cell. Conclusions: Th is analysis suggests that levels of provirus-bearing PBMC remain const ant during the natural course of HIV-1 infection, whereas plasma virus load typically increases logarithmically during the same period. The hypothesis that plasma virus levels are directly related to the number of infected cells may deserve reconsideration. (C) 1998 Lippincott Wi lliams & Wilkins.