Heterosexual risk of HIV-1 infection per sexual act: systematic review and meta-analysis of observational studies.

We did a systematic review and meta-analysis of observational studies of the risk of HIV-1 transmission per heterosexual contact. 43 publications comprising 25 different study populations were identified. Pooled female-to-male (0.04% per act [95% CI 0.01-0.14]) and male-to-female (0.08% per act [95% CI 0.06-0.11]) transmission estimates in high-income countries indicated a low risk of infection in the absence of antiretrovirals. Low-income country female-to-male (0.38% per act [95% CI 0.13-1.10]) and male-to-female (0.30% per act [95% CI 0.14-0.63]) estimates in the absence of commercial sex exposure (CSE) were higher. In meta-regression analysis, the infectivity across estimates in the absence of CSE was significantly associated with sex, setting, the interaction between setting and sex, and antenatal HIV prevalence. The pooled receptive anal intercourse estimate was much higher (1.7% per act [95% CI 0.3-8.9]). Estimates for the early and late phases of HIV infection were 9.2 (95% CI 4.5-18.8) and 7.3 (95% CI 4.5-11.9) times larger, respectively, than for the asymptomatic phase. After adjusting for CSE, presence or history of genital ulcers in either couple member increased per-act infectivity 5.3 (95% CI 1.4-19.5) times versus no sexually transmitted infection. Study estimates among non-circumcised men were at least twice those among circumcised men. Low-income country estimates were more heterogeneous than high-income country estimates, which indicates poorer study quality, greater heterogeneity of risk factors, or under-reporting of high-risk behaviour. Efforts are needed to better understand these differences and to quantify infectivity in low-income countries.