The Impact of Genital Ulcers on HIV Transmission Has Been Underestimated—A Critical Review

In the early 1990s, several observational studies determined that genital ulcer disease (GUD), in either the index or the exposed person, facilitates HIV transmission. Several meta-analyses have since presented associated risk ratios (RR) over the baseline per-act transmission probability (PATP) usually in the range of 2–5. Here we review all relevant observational studies and meta-analyses, and show that the estimation of RRs was, in most cases, biased by assuming the presence of GUD at any time during long follow-up periods, while active genital ulcers were present in a small proportion of the time. Only two studies measured the GUD co-factor effect in PATPs focusing on acts in which ulcers were present, and both found much higher RRs (in the range 11–112). We demonstrate that these high RRs can be reconciled with the studies on which currently accepted low RRs were based, if the calculations are restricted to the actual GUD episodes. Our results indicate that the effect of genital ulcers on the PATP of HIV might be much greater than currently accepted. We conclude that the medical community should work on the assumption that HIV risk is very high during active genital ulcers.