HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 MESSENGER-RNA EXPRESSION IN PERIPHERAL-BLOOD CELLS PREDICTS DISEASE PROGRESSION INDEPENDENTLY OF THE NUMBERS OF CD4+ LYMPHOCYTES

To address the significance of human immunodeficiency virus (HIV) repl ication in peripheral blood mononuclear cells (PBMCs), we have used re verse transcriptase-initiated PCR to measure HIV-1 mRNA expression in PBMC specimens collected from a cohort of HIV-infected individuals dur ing a long-term prospective study. We found dramatic differences in HI V mRNA expression among individuals with very similar clinical and lab oratory indices, and this variation strongly correlated with the futur e course of the disease. No evidence of viral replication was detected in PBMCs from asymptomatic individuals who, thereafter, had normal le vels of CD4+ cells for at least 5 years. Irrespective of whether the C D4+ cell numbers were normal at the time of sampling, abundant express ion of HIV-1 mRNA in PBMCs predicted accelerated disease progression w ithin the next 2 years. Thus, independently of what may be the rate of HIV replication in other viral reservoirs, such as lymphatic tissue, the amount of HIV mRNA in PBMCs appears to reflect the subsequent deve lopment of HIV disease. We have also used the reverse transcriptase-in itiated PCR assay to demonstrate a transient response to 3'-azido-3'-d eoxythymidine treatment. Determination of HIV-1 mRNA expression in the PBMCs of infected individuals could, therefore, have significant clin ical utility as a prognostic indicator and as a means to guiding and m onitoring antiviral therapies.