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

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          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.

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          Most cited references122

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          Transmission dynamics of HIV infection.

          Simple mathematical models of the transmission dynamics of human immunodeficiency virus help to clarify some of the essential relations between epidemiological factors, such as distributed incubation periods and heterogeneity in sexual activity, and the overall pattern of the AIDS epidemic. They also help to identify what kinds of epidemiological data are needed to make predictions of future trends.
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            Combination antiretroviral strategies for the treatment of pregnant HIV-1-infected women and prevention of perinatal HIV-1 transmission.

            The Women and Infants Transmission Study is a prospective natural history study that has been enrolling HIV-1-infected pregnant women and their infants since 1989. To evaluate the impact of different antiretroviral regimens on perinatal HIV-1 transmission at the population level. Prospective cohort study. Plasma HIV-1 RNA levels were serially measured in 1542 HIV-1-infected women with singleton live births between January 1990 and June 2000. HIV-1 status of the infant. HIV-1 transmission was 20.0% (95% confidence interval [CI], 16.1%-23.9%) for 396 women who not receiving prenatal antiretroviral therapy; 10.4% (95% CI, 8.2%-12.6%) for 710 receiving zidovudine monotherapy; 3.8% (95% CI, 1.1%-6.5%) for 186 receiving dual antiretroviral therapy with no or one highly active drug (Multi-ART); and 1.2% (95% CI, 0-2.5%) for 250 receiving highly active antiretroviral therapy (HAART). Transmission also varied by maternal delivery HIV RNA level: 1.0% for 30,000 copies/mL (p =.0001 for trend). The odds of transmission increased 2.4-fold (95% CI, 1.7-3.5) for every log10 increase in delivery viral load. In multivariate analyses adjusting for maternal viral load, duration of therapy, and other factors, the odds ratio for transmission for women receiving Multi-ART and HAART compared with those receiving ZDV monotherapy was 0.30 (95% CI, 0.09-1.02) and 0.27 (95% CI, 0.08-0.94), respectively. Levels of HIV-1 RNA at delivery and prenatal antiretroviral therapy were independently associated with transmission. The protective effect of therapy increased with the complexity and duration of the regimen. HAART was associated with the lowest rates of transmission.
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              Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial.

              Nonoxynol-9 (rINN, nonoxinol-9) is an over-the-counter spermicide that has in-vitro anti-HIV-1 activity. Results of studies of its effectiveness in prevention of HIV-1 infection in women have been inconclusive. We aimed to assess effectiveness of this vaginal gel. We did a randomised, placebo-controlled, triple-blinded, phase 2/3 trial with COL-1492, a nonoxynol-9 vaginal gel, in 892 female sex workers in four countries: Benin, Côte d'Ivoire, South Africa, and Thailand. 449 women were randomly allocated nonoxynol-9 and 443 placebo. Primary endpoint was incident HIV-1 infection. Secondary endpoints included Neisseria gonorrhoeae and Chlamydia trachomatis infections. Analysis was by intention to treat. 765 women were included in the primary analysis. HIV-1 frequency in nonoxynol-9 users was 59 (16%) of 376 compared with 45 (12%) [corrected] of 389 in placebo users (402.5 vs 435.0 woman-years; hazard ratio adjusted for centre 1.5; 95% CI 1.0-2.2; p=0.047). 239 (32%) women reported use of a mean of more than 3.5 applicators per working day, and in these women, risk of HIV-1 infection in nonoxynol-9 users was almost twice that in placebo users (hazard ratio 1.8; 95% CI 1.0-3.2). 516 (68%) women used the gel less frequently than 3.5 times a day, and in these, risk did not differ between the two treatments. No significant effect of nonoxynol-9 on N gonorrhoeae (1.2; 0.9-1.6) or C trachomatis (1.2; 0.8-1.6) infections was reported. This study did not show a protective effect of COL-1492 on HIV-1 transmission in high-risk women. Multiple use of nonoxynol-9 could cause toxic effects enhancing HIV-1 infection. This drug can no longer be deemed a potential HIV-1-prevention method. Assessment of other microbicides should continue.
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                Author and article information

                Journal
                Int J Epidemiol
                ije
                intjepid
                International Journal of Epidemiology
                Oxford University Press
                0300-5771
                1464-3685
                August 2010
                20 April 2010
                20 April 2010
                : 39
                : 4
                : 1048-1063
                Affiliations
                1Department of Infectious Disease Epidemiology, MRC Centre for Outbreak Analysis and Modelling, Faculty of Medicine, Imperial College London, London, UK, 2Centre for the Mathematical Modelling of Infectious Disease, Infectious Disease Epidemiology Unit, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK, 3Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, UK and 4URESP, Centre de recherche FRSQ du CHA universitaire de Québec, Québec, Canada
                Author notes
                *Corresponding author. MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, St Mary’s Campus, Norfolk Place, Paddington, London W2 1PG, UK. E-mail: r.baggaley@ 123456imperial.ac.uk
                Article
                dyq057
                10.1093/ije/dyq057
                2929353
                20406794
                9316d63a-74d8-4b5b-ac08-f52b41b65d90
                Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2010

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 February 2010
                Categories
                Infectious Disease

                Public health
                hiv,haart,meta-analysis,transmission probability,anal intercourse,review,infectivity
                Public health
                hiv, haart, meta-analysis, transmission probability, anal intercourse, review, infectivity

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