Simian immunodeficiency virus disease course is predicted by the extent ofvirus replication during primary infection

To elucidate the relationship between early viral infection events and immu nodeficiency virus disease progression, quantitative-competitive and branch ed-DNA methods of simian immunodeficiency virus (SIV) RNA quantitation were cross-validated and used to measure viremia following infection of rhesus macaques with the pathogenic STVmac251 virus isolate. Excellent correlation between the methods suggests that both accurately approximate SIV copy num ber. Plasma viremia was evident 4 days postinfection, and rapid viral expan sion led to peak viremia levels of 10(7) to 10(9) SIV RNA copies/ml by days 8 to 17. Limited resolution of primary viremia was accompanied by relative ly short, though variable, times to the development of AIDS (81 to 630 days ). The persistent high-level viremia observed following intravenous inocula tion of SIVmac251 explains the aggressive disease course in this model. Sur vival analyses demonstrated that the disease course is established 8 to 17 days postinfection, when peak viremia is observed. The most significant pre dictor of disease progression was the extent of viral decline following pea k viremia; larger decrements in viremia were associated with both lower ste ady-state viremia (P = 0.0005) and a reduced hazard of AIDS (P = 0.004). Th e data also unexpectedly suggested that following SIVmac251 infection, anim als with the highest peak viremia were better able to control virus replica tion rather than more rapidly developing disease. Analysis of early viral r eplication dynamics should help define host responses that protect from dis ease progression and should provide quantitative measures to assess the ext ent to which protective responses may be induced by prophylactic vaccinatio n.