Virologic and immunologic determinants of heterosexual transmission of human immunodeficiency virus type 1 in Africa

More than 80% of the world's HIV-infected adults live in sub-Saharan Africa , where heterosexual transmission is the predominant mode of spread. The vi rologic and immunologic correlates of female-to-male (FTM) and male-to-fema le (MTF) transmission are not well understood. A total of 1022 heterosexual couples with discordant HIV-1 serology results (one partner HIV infected, the other HIV uninfected) were enrolled in a prospective study in Lusaka, Z ambia and monitored at 3-month intervals. A nested case-control design was used to compare 109 transmitters and 208 nontransmitting controls with resp ect to plasma HIV-1 RNA (viral load, VL), virus isolation, and CD4(+) cell levels. Median plasma VL was significantly higher in transmitters than nont ransmitters (123,507 vs. 51,310 copies/ml, p < 0.001). In stratified multiv ariate Cox regression analyses, the risk ratio (RR) for FTM transmission wa s 7.6 (95% CI: 2.3, 25.5) for VL <greater than or equal to> 100,000 copies/ ml and 4.1 (95% CI: 1.2, 14.1) for VL between 10,000 and 100,000 copies/ml compared with the reference group of,10,000 copies/ml. Corresponding RRs fo r MTF transmission were 2.1 and 1.2, respectively, with 95% CI both boundin g 1. Only 3 of 41 (7%) female transmitters had VL, 10, 000 copies/ml compar ed with 32 of 93 (34%) of female nontransmitters (p, 0.001). The transmissi on rate within couples was 7.7/100 person-years and did not differ from FTM (61/862 person-years) and MTF (81/978 person-years) transmission. We concl ude that the association between increasing plasma viral load was strong fo r female to male transmission, but was only weakly predictive of male to fe male transmission in Zambian heterosexual couples. FTM and MTF transmission rates were similar. These data suggest gender-specific differences in the biology of heterosexual transmission.