Decline of simian immunodeficiency virus (SIV)-specific cytotoxic T lymphocytes in the peripheral blood of long-term nonprogressing macaques infectedwith SIVmac32H-J5

The evolution of simian immunodeficiency virus (SIV)-specific cytotoxic T l ymphocyte precursors (CTLps) and their relationship with virus replication were studied in SIV-infected macaques. After primary viremia, 3 of 8 macaqu es lost culturable virus and polymerase chain reaction-detectable provirus in peripheral blood. Although proviral DNA persisted in the spleen and lymp h nodes, virus loads were below or barely above detection levels. Throughou t the study, the 3 macaques remained asymptomatic, with stable CD4(+) cell counts. These findings were associated with the detection of CTLps directed against both structural and regulatory SIV proteins. The response peaked d uring the first 7 months of infection but waned subsequently, CTLps increas ed after rechallenge of 1 macaque, suggesting that limited antigenic stimul ation contributed to their disappearance from circulation. Transient viremi a with increasing CTLp frequencies and antibody titers also suggested at le ast partial susceptibility to reinfection. These findings bear implications for vaccination strategies aimed at inducing protective CTLs against lenti viruses.