Elsevier

The Lancet Infectious Diseases

Volume 9, Issue 2, February 2009, Pages 118-129
The Lancet Infectious Diseases

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

https://doi.org/10.1016/S1473-3099(09)70021-0 Get rights and content

Summary

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.

Introduction

Since the beginning of the HIV epidemic, mother-to-child transmission and iatrogenic transmission through contaminated blood products and unsafe injections have decreased because of improved health procedures and treatment options, particularly in high-income countries.1, 2, 3, 4, 5 However, the notion that different patterns of sexual behaviours and/or biological factors such as male circumcision and genital ulcer disease (GUD) can explain worldwide differences in heterosexual epidemic size has been questioned.6, 7, 8, 9 Some believe that sexual transmission has been overestimated, whereas iatrogenic transmission has been underestimated.10, 11, 12 Quantification of the risk of HIV infection after sexual intercourse with an infected partner is needed to better understand the epidemiology of HIV infection worldwide and to enable appropriate public-health decisions to be taken.

Sexual transmission estimates fall broadly into two categories: per-act transmission probabilities,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 which quantify the risk of infection per sexual contact, and per-partner transmission probabilities,13, 24, 25, 26, 27 which measure the cumulative risk of infection over many sex acts during a partnership. In both cases, transmission probabilities depend on the infectiousness of the HIV-infected partner and the susceptibility of the HIV-uninfected partner. Infectiousness and susceptibility depend on behavioural, biological, genetic, and immunological risk factors of the host and the virus.5, 6, 21, 22, 23, 24, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42 Per-act transmission probabilities are methodologically difficult to measure.43 The time of seroconversion of the index case and the transmission to his or her partner, the number of unprotected sex acts, duration of exposure to HIV, and potential HIV cofactors among the index cases and the susceptible partners at the time of transmission are rarely known precisely, especially for time-varying cofactors, such as recurrent sexually transmitted infections (STIs).5, 16, 43, 44, 45

Early narrative or methodological reviews have reported a limited selection of per-act estimates.10, 11, 12, 42, 46, 47, 48 More recently, Powers and colleagues49 published a systematic review of per-act HIV-1 transmission probabilities of 27 studies based on 15 unique study populations. Our systematic review extends this work by including 43 publications based on 25 different study populations. Our objectives were to provide summary estimates of HIV-1 transmission probabilities per heterosexual contact, to do in-depth univariate and multivariate meta-regression analyses to explore the variation across study estimates, and to estimate the influence of key risk factors on infectivity. The review focuses on HIV-1, which is more pathogenic and prevalent than HIV-2.50, 51

Section snippets

Search strategy

The literature search (up to Sept 6, 2008) was done in three stages. First, PubMed, Science Direct, and NLM Gateway online databases were searched to September, 2006, by use of the following search terms: “HIV transmission probability” OR “HIV transmission probabilities” OR “HIV infectivity” OR “HIV infectiousness” NOT “perinatal” NOT “mother to child” NOT “mother-to-child”, and by replacing “HIV” by the terms “LAV”, “HTLV-III” and “HTLV III”. PubMed was searched by titles. Science Direct and

Study selection

Figure 1 shows details of the study selection procedure. Most studies were excluded because they were risk-factor analyses, reported non-sexual or homosexual transmission, per-partner estimates, or did not provide enough information to derive an estimate. 42 studies reporting at least one per-act heterosexual HIV-1 transmission estimate and 13 studies reporting sufficient information to derive an estimate were identified from the PubMed search and in one case by personal communication. 14

Discussion

Our systematic review and meta-analysis of HIV-1 transmission probabilities per heterosexual act updates and extends the findings of a recent similar review.49 We confirmed the earlier observation of substantial heterogeneity in per-act estimates,49 provided sex-specific transmission estimates, and identified additional sources of heterogeneity by exploring interactions between covariates. We also reported the influence of key risk factors on infectivity in terms of relative risk (risk ratios),

Conclusions

Our results indicated higher transmission probabilities for low-income than for high-income country studies. The greater heterogeneity of low-income country estimates is itself interesting and may suggest poorer study quality, greater heterogeneity in risk factors, or greater under-reporting of high-risk behaviour in these studies. More research is needed to better understand these differences, and particularly the low estimates from Rakai.19, 20 Greater heterogeneity may also be caused by

Search strategy and selection criteria

These are described in detail in the Methods section.

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