THE EXTENT OF EARLY VIRAL REPLICATION IS A CRITICAL DETERMINANT OF THE NATURAL-HISTORY OF SIMIAN IMMUNODEFICIENCY VIRUS-INFECTION

Different patterns of viral replication correlate with the natural his tory of disease progression in humans and macaques infected with human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency vir us (SIV), respectively. However, the viral and host factors influencin g these patterns of viral replication in vivo are poorly understood. W e intensively studied viral replication in macaques receiving identica l inocula of SIV. Marked differences in viral replication patterns wer e apparent within the first week following inoculation, a time prior t o the development of measurable specific immune effector responses to viral antigens. Plasma viral RNA levels measured on day 7 postinoculat ion correlated with levels measured in the postacute phase of infectio n. Differences in the susceptibility of host cells from different anim als to in vitro SIV infection correlated with the permissiveness of th e animals for early in vivo viral replication and hence with the posta cute set point level of plasma viremia. These results suggest that hos t factors that exert their effects prior to full development of specif ic immune responses are critical in establishing the in vivo viral rep lication pattern and associated clinical course in subjects infected w ith SIV and, by extension, with HIV-1.