Correlates of resistance to HIV-1 infection in homosexual men with high-risk sexual behaviour.

FA Koning, CA Jansen, J Dekker, RA Kaslow, N Dukers, D van Baarle, M Prins, H Schuitemaker

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34 Citations (Scopus)


Objective: To investigate possible correlates of HIV resistance in participants from the Amsterdam Cohort of Homosexual men who have remained HIV seronegative despite high-risk sexual behaviour. Design/methods: We studied in vitro HIV-1 susceptibility and adaptive and innate immunity in 29 high-risk seronegative (HRSN) and 15 HIV-negative pre-seroconversion (pre-SC) homosexual men from the same Amsterdam Cohort Study (ACS) who seroconverted to HIV-1 positive during active follow-up. Host genetics were compared between HRSN and HIV-positive ACS participants. Results: We found lower in vitro susceptibility for a CCR5-using (R5) HIV-1 variant, higher RANTES production levels, but no difference in coreceptor expression in HRSN as compared with pre-SC controls. Reduced R5 in vitro susceptibility of two HRSN tested was restored to normal levels by addition of antibodies against beta-chemokines. A higher proportion of HRSN carried the SDF-1 3'A variant and HLA-A*11, A*31 and Cw*15 alleles. ELIspot analysis with HIV-1 peptide stimulation revealed low frequencies of HIV-1-specific CD8 interferon-gamma producing cytotoxic T cells in both HRSN and pre-SC controls. Conclusions: Low in vitro R5 susceptibility of cells from the HRSN men was due to beta-chemokine mediated inhibition of virus replication. The presence of HIV-1 specific cytotoxic T cells in both HRSN and pre-SC participants may signify exposure to the virus rather than protection from infection. Host genetic characteristics and other factors affecting innate immunity may contribute to differential resistance to HIV-1 infection among exposed seronegative individuals. (C) 2004 Lippincott Williams Wilkins
Original languageEnglish
Pages (from-to)1117 - 1126
Number of pages10
Issue number8
Publication statusPublished - 21 May 2004


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