Background: Infection of rhesus macaques with SIVmac239 results in persistent high-level viral replication, progressive immunodeficiency, and opportunistic infections or neoplasms typical of simian AIDS with a median survival of 1–2 yrs post-inoculation. We report on a macaque that spontaneously appears to have established sustained effective control of SIVmac239 infection.

Methods: Six (6) SIV-naïve Indian rhesus macaques were inoculated iv with 30 MID₅₀ of SIVmac239. Plasma viremia was monitored by a real time RT PCR assay. SIV-specific cellular immune responses were measured by LPA and IFN-γ ELISpot assays, using inactivated SIV or SIV peptides as stimuli.

Results: All 6 macaques showed peak plasma viral loads in the expected range (mean 73 x 10⁶ copy Eq/ml; range 17–190 x 10⁶) , 2–3 weeks post-inoculation (p.i.). 5 of 6 animals showed post-acute (mean for weeks 10,12,14,16, 20, 24 p.i.) viral load levels in the expected range (mean 21 x 10⁶; range 0.2–110 x 10⁶). After showing a peak of 66 x 10⁶, animal C59Z dramatically downregulated plasma viremia beginning approximately 6 weeks p.i., with an average viral load of 0.04 X 10⁶ from week 10–24, p.i. Over the subsequent nearly 1 year of follow up, C59Z has further controlled plasma viremia to < 20 copy Eq/mL. This virologic control is associated with strong LPA and ELISpot responses to inactivated SIV, and an unusual pattern of reactivity in peptide ELISpot assays, emphasizing determinants in pol.

Conclusions: After inoculation with SIVmac239, a SIV-naive rhesus macaque showed extraordinary, atypical, progressive control of viral replication associated with development of antiviral cellular immune responses of unusual specificity. Contributions to the observed virologic profile of cellular immune responses, humoral immunity, genetic factors, and possible viral changes are being investigated. Along with studies of 2 additional SIVmac239 infected animals we have identified with similar virologic profiles, this analysis may shed light on mechanisms of immune control of pathogenic primate lentivirus infection, with important implications for vaccine development.