Background:  Untreated HIV-1 patients with HLA-B*57 often have low viremia and delayed onset of clinically apparent immunodeficiency. This advantage has been consistently attributed to preferential and effective targeting of HIV Gag epitopes by B*57-restricted cytotoxic T lymphocytes. The objective of this study was to examine the rate of heterosexual HIV-1 transmission in chronically infected patients with HLA-B*57 and without the B*5701-specific haplotype found in Caucasians.

Methods:  HIV-1-discordant (1 partner HIV-1⁺ and the other HIV-1^–) Zambian couples were enrolled continuously into longitudinal studies, starting in 1995. HLA class I genotyping was performed for 438 couples who had at least 12 months of follow-up at the end of 2006. Logistic regression and Cox proportional hazard models were used to test the relationship between carriage of HLA-B*57 by the index (seroprevalent) partners and transmission of HIV-1 to their seronegative partners.

Results:  B*5703 is the dominant B*57 allele in Zambians, primarily on the A*30-Cw*18-B*57 haplotype (showing strong linkage disequilibrium). Compared with index partners without B*57, those with B*57 (n = 57) had lower viral load (–0.30 log₁₀) and delayed viral transmission to their seronegative partners (relative hazard, 0.61, p = 0.04). At the end of the 12-year (1995 to 2006) study, index partners with B*57 were less likely to be transmitters (odds ratio = 0.50, p = 0.05). These relationships were independent of the direction of transmission (male to female or female to male) and could be extended to 42 index partners with the B*57-Cw*18 haplotype (e.g., RH, 0.59, p = 0.05).

Conclusions:  The reduction in HIV-1 viral load associated with HLA-B*57 in HIV-1⁺ individuals can translate to delayed and reduced viral transmission in Zambia, where clade C HIV-1 infection is widespread.