To clarify the relationship between the number of provirus-bearing peripheral blood mononuclear cells (PBMC) and HIV-1 disease progression during the natural history of infection.
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.
Infected PBMC equivalents were determined by HIV-1 DNA quantitative competitive (QC)-PCR. The results were analysed with respect to HIV-1 disease stage and compared with a mathematical model of long-term HIV-1 disease progression.
PBMC HIV-1 DNA did not correlate with major indices of disease progression, including time 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 harbouring HIV-1 provirus was relatively constant throughout the clinical stages of HIV-1 infection, consistent with simulated data from a mathematical model of long-term HIV-1 infection. We also showed that a biased interpretation of the QC-PCR data may arise when the values are expressed as HIV-1 DNA copies per PBMC or per CD4 cell.
This analysis suggests that levels of provirus-bearing PBMC remain constant 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.