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

AIDS. 2004 May 21;18(8):1117-26. doi: 10.1097/00002030-200405210-00005.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology
  • Chemokine CCL5 / metabolism
  • Chemokines, CC / metabolism
  • Disease Susceptibility / virology
  • Genotype
  • HIV Seronegativity / immunology*
  • HIV-1 / immunology*
  • Heterozygote
  • Homosexuality, Male*
  • Homozygote
  • Humans
  • Immunity, Innate
  • Interferon-gamma / metabolism
  • Male
  • Retrospective Studies
  • Risk-Taking


  • Chemokine CCL5
  • Chemokines, CC
  • Interferon-gamma