Background: Heterosexual transmission of HIV-1 predominates in sub-Saharan Africa.

Objective: To identify immunogenetic determinants of viral transmission in a cohort of native Africans.

Methods: Cohabiting, HIV-1-discordant Zambian couples were enrolled for a longitudinal study between 1995–2002. Documented transmission of genetically similar virus from the seropositive (index) to the seronegative (recipient) partner established intra-couple linked HIV-1 transmission; detection of dissimilar viruses in index and recipient partners established unlinked transmission. Using appropriate regression models, we estimated the relative hazards (RHs) or odds (ROs) of HIV-1 seroconversion and transmission as functions of fully resolved HLA class II DRB1 and DQB1 genotypes. Analyses were adjusted for index partner age, gender, and virus load (HIV-1 RNA copies/ml of plasma).

Results: We analyzed 124-linked and 16-unlinked transmissions along with 152 non-transmission couples. Index partners bearing DRB1*1301 (RH = 0.54, p = 0.05) and the haplotype DRB1*1301 DQB1*0501 (RH = 0.47, p = 0.08) showed delayed viral transmission. Recipient partners with either DRB1*0301-DQB1*0201 (RH = 1.60, p = 0.009) or DRB1*1503-DQB1*0602 (RH = 1.67, p = 0.03) showed accelerated seroconversion. Adjustment for non-genetic host factors produced little change in these relationships. In similarly adjusted logistic regression analyses, all persistently seronegative (n = 152) differed from all seropositive (n = 432) partners with regard to DRB1*1302-DQB1*0604 (RO = 3.3, p = 0.003) and DRB1*1503-DQB1*0602 (RO = 0.53, p = 0.02).

Conclusions: HLA class II profiles in both partners of HIV-1-discordant Zambian couples may have played a modest role in heterosexual HIV-1 transmission. Optimal characterization of host genetic determinants of HIV infection would take account of genotypic variation in both partners.