Early viral replication dynamics predict clinical course in SIV infected macaques

In macaques receiving identical inocula of SIV, 3 different patterns of viral replication are observed, with stabilization of post-acute plasma viral load levels in different ranges. These different patterns are associated with different clinical courses and outcomes, ranging from rapid disease progression to death from AIDS in less than 6 months to long term non-progression (greater than 3 yrs). To better understand the factors that contribute to determining these different patterns and levels of viral replication in animals receiving identical inocula, we intensively studied (weekly, twice weekly, or daily) virologic and immunologic parameters from the time of inoculation through resolution of primary infection and into the post-acute phase of infection in 28 macaques, including 4 animals inoculated with a pathogenic molecularly cloned virus. Plasma viral load levels in the early post-inoculation period were highly correlated with levels established in post-acute infection (weeks 6-8), suggesting that the initial rate and extent of viral replication of virus upon infection is an important factor in helping to determine the eventual overall level of viral replication in the chronically infected animal ("set point"). The correlation with viral replication rates and levels during the very early period of infection, when specific antiviral immune responses such as effector CTLs are yet not optimally active, points to innate immunity and other host factors as potentially important host determinants contributing to the establishment of the viral replication set point in the post-acute phase of infection, perhaps by modulating the character, quality and consequences of the initial antigenic sensitization of specific antiviral immune responses. Finally, the intensive viral load analysis performed during this study facilitated detailed mathematical modeling of in vivo SIV viral replication dynamics.

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