7th Conference - Abstract 569

CCR5 Heterozygosity Is Associated with Preserved HIV-Specific Cellular Immune Responses in Recent Seroconverters

E. CONNICK*¹, R. SCHLICHTEMEIER¹, M. PURNER¹, K. SCHNEIDER¹, S. MAWHINNEY¹, T. CAMPBELL¹, D. KURITZKES¹, J. DOUGLAS², F. JUDSON², and R. SCHOOLEY¹. ¹Univ. of Colorado Hlth. Sci. Ctr., Denver; and ²Denver Hlth. and Hospitals, CO

HIV-specific cytotoxic T lymphocyte (CTL) activity was assayed in 15 prospectively identified untreated HIV seroconverters within the first 6 months of seroconversion. ⁵¹Cr release assays for env-, gag-, pol-, or nef-specific CTL activity using 14 day antigen-stimulated PBMC cultures revealed that all subjects responded to at least two HIV proteins whereas no activity was detected in 5 HIV-seronegative individuals. There was no correlation between the plasma virus set point, defined as the HIV plasma copy number at 6 months, and CTL recognition of any particular HIV antigen. Subjects with lower virus set points tended to respond to fewer antigens than others (Spearman's correlation=.537; p=0.054). The frequency of gag-specific precursor CTL (pCTL) was inversely correlated with the plasma virus set point (Spearman's correlation=-.772; p=0.0052). Two subjects achieved and maintained a plasma HIV RNA copy number <400 during the first year. These subjects had the highest gag-specific pCTL frequencies, and were the only CCR5 heterozygotes in the sample. Serial lymphoproliferation assays for envelope, p24, and p66 antigens were performed in 3 of the 15 subjects including one of the CCR5 heterozygotes within the first year of seroconversion. Two of the three subjects had HIV-specific lymphocyte proliferative responses including the CCR5 heterozygote, although responses in both subjects waned over time.
Conclusion: These data contradict the hypothesis that a broad HIV-specific CTL response is distinctive of individuals with low plasma virus set points. The concordance between CCR5 heterozygosity and vigorous gag-specific pCTL responses suggests that preservation of HIV-specific CTL responses may be the consequence of restricted HIV replication rather than the cause of low virus set points in untreated individuals.

Key Words: CCR5, CTL, seroconverter