HIV transmission risk through anal intercourse: systematic review, meta-analysis and implications for HIV prevention

Abstract

Background: The human immunodeficiency virus (HIV) infectiousness of anal intercourse (AI) has not been systematically reviewed, despite its role driving HIV epidemics among men who have sex with men (MSM) and its potential contribution to heterosexual spread. We assessed the per-act and per-partner HIV transmission risk from AI exposure for heterosexuals and MSM and its implications for HIV prevention.

Methods: Systematic review and meta-analysis of the literature on HIV-1 infectiousness through AI was conducted. PubMed was searched to September 2008. A binomial model explored the individual risk of HIV infection with and without highly active antiretroviral therapy (HAART).

Results: A total of 62,643 titles were searched; four publications reporting per-act and 12 reporting per-partner transmission estimates were included. Overall, random effects model summary estimates were 1.4% [95% confidence interval (CI) 0.2-2.5)] and 40.4% (95% CI 6.0-74.9) for per-act and per-partner unprotected receptive AI (URAI), respectively. There was no significant difference between per-act risks of URAI for heterosexuals and MSM. Per-partner unprotected insertive AI (UIAI) and combined URAI-UIAI risk were 21.7% (95% CI 0.2-43.3) and 39.9% (95% CI 22.5-57.4), respectively, with no available per-act estimates. Per-partner combined URAI-UIAI summary estimates, which adjusted for additional exposures other than AI with a 'main' partner [7.9% (95% CI 1.2-14.5)], were lower than crude (unadjusted) estimates [48.1% (95% CI 35.3-60.8)]. Our modelling demonstrated that it would require unreasonably low numbers of AI HIV exposures per partnership to reconcile the summary per-act and per-partner estimates, suggesting considerable variability in AI infectiousness between and within partnerships over time. AI may substantially increase HIV transmission risk even if the infected partner is receiving HAART; however, predictions are highly sensitive to infectiousness assumptions based on viral load.

Conclusions: Unprotected AI is a high-risk practice for HIV transmission, probably with substantial variation in infectiousness. The significant heterogeneity between infectiousness estimates means that pooled AI HIV transmission probabilities should be used with caution. Recent reported rises in AI among heterosexuals suggest a greater understanding of the role AI plays in heterosexual sex lives may be increasingly important for HIV prevention.

Figure 1

Forest plot of studies estimating HIV transmission probabilities for AI expressing risk as (a) per-act and (b) per-partner. For crude estimates (unfilled boxes), the size of box represents relative study sample size. Adjusted estimate (filled Rhombus), Crude estimate based on x number of seroconverting partners among n couples with an infected index partner (open square), Summary estimate (filled squre)

Figure 2

Relation between per-partner HIV transmission risk (cumulative probability of HIV transmission) and the number of sexual acts with an HIV infected partner, using our summary per-act URAI estimate of 1.4% (95% CI 0.2–2.5). The intersection between the modelled per-partner HIV transmission risk (y-axis) and our meta-analytic per-partner combined URAI–UIAI summary estimates (plotted as horizontal lines) predicts the required average number of acts per partnership (x-axis), under our model assumptions (see ‘Methods’ section). Adjusted estimates control for exposures due to multiple partners and crude estimates do not. (a) All acts assumed to be URAI; (b) 50% acts URAI, 50% acts UIAI, assuming that per-act UIAI has the same HIV transmission probability as penile–vaginal intercourse (summary estimate of per-act penile–vaginal intercourse, male-to-female transmission for developing countries: 0.3%; (c) as for (b) but UIAI HIV transmission probability is 0.6%. Competing risk from UIAI increases the total number of unprotected acts necessary for transmission per partnership only by relatively modest amounts, especially when the increase in transmission probability of UIAI compared with VI is large, because UIAI infectiousness becomes closer to that of URAI.

Figure 3

Relation between per-partner HIV risk (cumulative probability of HIV transmission) and the number of all sexual acts (whether penile–vaginal or penile–anal) that uninfected MSM or heterosexual women are exposed to with HIV-infected men, exploring the impact of different frequencies of URAI within the partnership (if in a monogamous HIV discordant relationship) or among all sexual HIV exposures that an uninfected individual encounters. Frequency of sexual acts involving URAI: 0–20% represent ranges for women in heterosexual partnerships, with the remainder of sexual exposures assumed to be penile–vaginal; 50% represents MSM partnerships where each partner practises URAI and UIAI equally often; 100% represents MSM where the seronegative partner is always receptive. Scenario (a) represents the impact of URAI on per-partner HIV risk assuming a constant per-act probability for URAI (1.4%, Table 1) and for penile–vaginal intercourse (summary estimate of per-act penile–vaginal intercourse, male-to-female transmission for developing countries: 0.3%; we assume, in the absence of per-act HIV estimates for UIAI identified by our review, that HIV transmission probability is the same as for female-to-male penile–vaginal intercourse). Scenario (b) uses Function 1 to investigate impact of HAART, predicting per-partner HIV risk within a discordant couple where the index male has successful viral suppression due to HAART. Scenario (c) investigates the same, by using Function 2 (note change of y-axis scale). Scenarios (d) and (e) use Function 2 (separating graphs for women and MSM for clarity), additionally including viral rebound as a result of treatment failure for a proportion of the duration of exposure. The derived relationship between URAI infectiousness and plasma viral load calculated in Function 2 is illustrated in Supplementary Figure S3 (available as Supplementary data at IJE online).