PLASMA VIREMIA IN MACAQUES INFECTED WITH SIMIAN IMMUNODEFICIENCY VIRUS - PLASMA VIRAL LOAD EARLY IN INFECTION PREDICTS SURVIVAL

A reliable method for the quantitation of plasma viremia in nonhuman p rimates infected with simian immunodeficiency virus (SIV) and related viruses is described. This method is based on an established quantitat ive-competitive PCR format and includes a truncated control for intern al assay calibration, Optimization of assay conditions has significant ly improved amplification specificity, and interassay variability is c omparable to that of commercially available assays for human immunodef iciency virus (HIV) quantitation, This procedure was used to monitor v iral loads in a group of Macaca mulatta animals that were infected wit h SIVsmE660 for over 2 years. Highly diverse profiles of plasma viremi a were observed among animals, and high viral loads were associated wi th more rapid disease progression, Spearman rank correlation analyses were done for survival versus three parameters of viral load: plasma v iremia, p27 core antigen, and frequency of infected peripheral blood m ononuclear cells. Plasma viremia had the strongest overall correlation and was significantly (P < 0.05 to P < 0.01) associated with survival at 10 of the 13 time points examined, Plasma viremia did not correlat e with survival during the primary viremia phase; however, the strengt h of this correlation increased with time postinfection and, remarkabl y, viremia levels as early as week 6 postinfection were highly predict ive (P < 0.01) of relative survival. These findings are consistent wit h the available clinical data concerning viral load correlates early i n HIV infection, and they provide further support for the view that di sease outcome in lentiviral infection may be largely determined by eve nts that occur shortly after infection.