Late seroconversion in HIV-resistant Nairobi prostitutes despite pre-existing HIV-specific CD8(+) responses

Resistance to HIV infection in a small group of Kenyan sex workers is assoc iated with CD8(+)-lymphocyte responses to HIV cyto toxic T-lymphocyte (CTL) epitopes, Eleven prostitutes meeting criteria for HIV resistance seroconve rted between 1996 and 1999. The occurrence and specificity of preexisting H IV-1 epitope-specific responses were examined using the IFN-gamma enzyme-li nked immunospot assay, and any epitopes recognized were cloned and sequence d from the infecting viral isolate. Immunologic and behavioral variables me re compared between late seroconverters and persistently uninfected sex wor ker controls. HIV-1 CTL epitope responses were present in four of six cases , 5-18 months before seroconversion, and their presence was confirmed by bu lk CTL culture. A possible viral escape mutation was found in one of six ep itopes. The key epidemiologic correlate of late seroconversion was a reduct ion in sex work over the preceding year. In persistently uninfected control s, a break from sex work was associated with a loss of HIV-specific CD8(+) responses. Late seroconversion may occur in HIV-1-resistant sex workers des pite preceding HIV-specific CD8(+) responses. Seroconversion generally occu rs in the absence of detectable CTL escape mutations and may relate to the waning of HIV-specific CD8(+) responses due to reduced antigenic exposure.