Background: Some individuals remain HIV-seronegative despite high-risk exposure to the virus.

Methods: We studied 29 homosexual men from the Amsterdam Cohort with high-risk sexual behavior for possible correlates of HIV-1 resistance. As controls we used pre-seroconversion (pre-SC) samples from HIV negative homosexual men who seroconverted for HIV-1 antibodies during active follow-up in the same cohort study.

Results:  For the high-risk seronegative individuals (HRS) as a group we found lower in vitro susceptibility for a CCR5-using (R5) HIV-1 variant, higher RANTES production levels, but no difference in coreceptor expression as compared to pre-SC controls. In vitro R5 susceptibility was restored to normal levels by addition of antibodies against β-chemokines. We found a higher frequency of the SDF-1 3’A allele and higher frequencies of HLA type 1 A11, A31, and Cw15 alleles in the HRS. One HRS individual was homozygous for the Δ32 CCR5 allele. Low frequencies of HIV-specific IFN-γ producing cells were detected in both HRS and pre-SC controls.

Conclusions:  Low in vitro susceptibility of the HRS PBMC was due to β-chemokine mediated inhibition of virus replication. The presence of HIV-specific CTL in both HRS and pre-SC samples indicates that cellular immunity not necessarily reflects protection from infection, but rather exposure to the virus. The mechanism of protection associated with SDF-1 3’A and HLA type remains to be studied. We conclude that different host factors may influence resistance to HIV-1 infection, including innate immunity and host genetic make-up.

Keywords: Resistance to HIV-1 infection; b-chemokine production; CTL