Abstract
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.
Highlights
It is widely accepted that genital ulcer disease (GUD) caused by various sexually transmitted infections (STI) facilitates sexual transmission of human immunodeficiency viruses (HIV)
The meta-analysis of per-act transmission probability (PATP) published by Boily et al, 2009 [16] is a comprehensive and influential review of HIV-1 PATPs, and associated co-factors
A meta-analysis published by Looker et al, 2017 [19] reviewed many studies measuring or estimating the effects of Herpes simplex virus type 2 (HSV-2) infection on HIV transmission, but did not focus on PATPs
Summary
It is widely accepted that genital ulcer disease (GUD) caused by various sexually transmitted infections (STI) facilitates sexual transmission of human immunodeficiency viruses (HIV). It may cause bleeding, and it causes local inflammation and an upregulation of CCR5 expression in T cells, favouring local HIV replication, and increasing the odds of transmission from the index partner. STIs and GUDs appear to be more important determinants of HIV transmission in Africa when HIV epidemics are not yet mature, fueled by high-risk groups [4–6]. With the current UNAIDS 95-95-95 targets (95% diagnosed among all people living with HIV, 95% on antiretroviral therapy (ART) among diagnosed, and 95% virally suppressed), it is expected that the epidemic will again become concentrated in disadvantaged and high-risk groups
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