Levels of HIV-infected peripheral blood cells remain stable throughout the natural history of HIV-1 infection. Swiss HIV Cohort Study.
OBJECTIVE
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.


METHODS
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 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.


RESULTS
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.


CONCLUSIONS
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.
Cone
R W
RW
Department of Internal Medicine, University Hospital, Zurich, Switzerland.
Gowland
P
P
Opravil
M
M
Grob
P
P
Ledergerber
B
B
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008432:Mathematical Computing; D008875:Middle Aged; D008954:Models, Biological; D012189:Retrospective Studies
D004279:DNA, Viral