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Resistance to HIV infection in a small group of Kenyan sex workers is associated with CD8+-lymphocyte responses to HIV cytotoxic T-lymphocyte (CTL) epitopes. Eleven prostitutes meeting criteria for HIV resistance seroconverted between 1996 and 1999. The occurrence and specificity of preexisting HIV-1 epitope-specific responses were examined using the IFN-gamma enzyme-linked immunospot assay, and any epitopes recognized were cloned and sequenced from the infecting viral isolate. Immunologic and behavioral variables were compared between late seroconverters and persistently uninfected sex worker controls. HIV-1 CTL epitope responses were present in four of six cases, 5-18 months before seroconversion, and their presence was confirmed by bulk CTL culture. A possible viral escape mutation was found in one of six epitopes. The key epidemiologic correlate of late seroconversion was a reduction in sex work over the preceding year. In persistently uninfected controls, 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 despite preceding HIV-specific CD8+ responses. Seroconversion generally occurs in the absence of detectable CTL escape mutations and may relate to the waning of HIV-specific CD8+ responses due to reduced antigenic exposure.

Original publication

DOI

10.1172/JCI10714

Type

Journal article

Journal

J Clin Invest

Publication Date

02/2001

Volume

107

Pages

341 - 349

Keywords

Adult, Amino Acid Sequence, CD8-Positive T-Lymphocytes, Cohort Studies, Enzyme-Linked Immunosorbent Assay, Epitopes, Female, HIV Antigens, HIV Infections, HIV Seronegativity, HIV Seropositivity, HIV-1, Humans, Interferon-gamma, Kenya, Lymphocyte Count, Risk-Taking, Sex Work, Sexual Behavior, Time Factors