15th International AIDS Conference Bangkok, Thailand - July 11-16, 2004

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. TuOrA1141)

Zhu T, Zioni R, Zhu H, Xu Y, Lee J, Nelson P, Andrus T, Llewellyn N, Nickle D, Chang Y, Mullins J, Corey L, McElrath J
University of Washington, Seattle, United States

BACKGROUND: In the past 6 years, we have conducted a study to identify HIV-1 infection in exposed-seronegatives (ES) persons who reported repeated unprotected sexual activities with multiple HIV-1-infected partners.

METHODS: HIV-1 sequences were PCR-amplified from ES and their long-term sexual partners, and were analyzed with programs including PAUP* and MEGA.

RESULTS: HIV-1 sequences were identified in 12 out of 94 ES individuals. Of these 12 infected ES, 2 have remained seronegative and healthy with persistent HIV-1 DNA at levels (mean, 0.05 copies/million cells) below the detection limit of routine assays. The other 10 HIV-1-infected ES seroconverted later. We analyzed HIV-1 env sequences in 5 of the 10 late seroconverters (LSC) and one ES whose HIV-1 infected, long-term sexual partners were identified, and found that none of the exposed individuals were infected or superinfected by the long-term sexual partners. HIV-1 env genetic distances between the breakthrough virus in LSC and their partner virus were significantly higher than those of distances between each pair of HIV-1 sequences randomly chosen from GenBank (P< 0.001). A higher rate of non-synonymous mutations (dN) (P< 0.05), but not synonymous mutations (dS) (P = 0.48), was found between 4 LSC who had HIV-1-specific CD8+ responses (CTL) before seroconversion and their long-term partners, as comp ared to random HIV-1 pairs. In contrast, the dS but not dN was higher in the LSC who had no detectable CTL pre-seroconversion. Significant difference in dN but not dS was found between LSC and partners HIV-1 sequences corresponding to multiple CTL epitopes detected pre-seroconversion.

CONCLUSIONS: Breakthrough HIV-1 strains in ES/LSC are distinct from those of their long-term sexual partners, indicating that repeated virus exposures might protect HIV-1 similar to that of the partners, but allow divergent viral strains to infect. Pre-infection CTL might provide partial protection against HIV-1 infection and serve as one of the selective forces on breakthrough HIV-1 in LSC.

040711
TuOrA1141

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