P09-17. Evolution of HLA-B*5703 HIV-1 escape mutations and their impact on HIV-1 replicative capacity

Abstract

Results HLA-B*5703-restricted CTL responses select for escape mutations in three Gag p24 epitopes, in a predictable order, and we show here that the accumulation of these mutations sequentially reduces viral replicative capacity in vitro. Despite this, in vivo data demonstrate that ultimately there is an increase in viral load concomitant with evasion of all three HLA-B*5703-restricted CTL responses. In HLA-B*5703-mismatched recipients, the previously described early benefit of transmitted HLA-B*5703-associated escape mutations is abrogated by the increase in viral load coincident with reversion. Conclusion These data demonstrate that, while costly escape from CTL responses can progressively attenuate the virus, high viral loads develop in the absence of adequate, continued CTL responses. These data underline the need for a CTL vaccine against multiple conserved epitopes. from AIDS Vaccine 2009 Paris, France. 19–22 October 2009