The replicative capacity of rhesus macaque peripheral blood mononuclear cells for simian immunodeficiency virus in vitro is predictive of the rate ofprogression to AIDS in vivo

Survival of rhesus macaques (Macaca mulatta) experimentally infected with s imian immunodeficiency virus (SIV) varies significantly from animal to anim al. Some animals die within 2 months while others survive for more than 5 y ears, even when identical inocula are used. This diversity in survival crea tes a significant problem in the design of therapeutic and vaccine trials u sing the SIV-macaque model because the use of small numbers of animals may provide results that are misleading. Identifying an in vitro assay that cou ld determine the survival of monkeys prior to infection would prove extreme ly useful for stratifying experimental groups. Analysis of the survival of a cohort of 59 control animals obtained from over a decade of vaccine and t herapeutic trials has demonstrated that the ability of peripheral blood mon onuclear cells (PBMC) from a naive animal to produce virus in vitro was hig hly predictive of disease progression in vivo following experimental inocul ation. Animals classified in vitro as high producers of virus progressed to disease significantly more rapidly than animals classified as either low ( P = 0.002) or intermediate (P = 0.013) producers of virus. The hierarchy of high and low virus production was maintained in purified CD4(+) T cell cul tures, indicating that th is phenotype is an intrinsic property of the CD4( +) T cell itself. These findings should significantly aid in the design of vaccine and therapeutic trials using the SIV-macaque model. Furthermore, si nce these studies suggest that the rate of virus replication is controlled by innate characteristics of the individual, they provide new insight into the pathogenesis of AIDS.