HIV transmission risk through anal intercourse: systematic review, meta-analysis and implications for HIV prevention
01 Aug 2010-International Journal of Epidemiology (Oxford University Press)-Vol. 39, Iss: 4, pp 1048-1063
TL;DR: It was 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.
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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University of Colorado Denver1, University of California, San Francisco2, Asociación Civil Impacta Salud y Educación3, Oswaldo Cruz Foundation4, Chiang Mai University5, Federal University of Rio de Janeiro6, University of Cape Town7, Brown University8, University of São Paulo9, National Institutes of Health10
TL;DR: Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects and Detectable blood levels strongly correlated with the prophylactic effect.
Abstract: The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at en rollment, and 100 became infected during follow-up (36 in the FTC–TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P = 0.005). In the FTC–TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC–TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P = 0.57). Conclusions Oral FTC–TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foun dation; ClinicalTrials.gov number, NCT00458393.)
4,247 citations
TL;DR: It is shown that the high probability of transmission per act through receptive anal intercourse has a central role in explaining the disproportionate disease burden in MSM and prevention strategies that lower biological transmission and acquisition risks offer promise.
1,369 citations
TL;DR: The findings suggest that transgender women are a very high burden population for HIV and are in urgent need of prevention, treatment, and care services.
Abstract: Summary Background Previous systematic reviews have identified a high prevalence of HIV infection in transgender women in the USA and in those who sell sex (compared with both female and male sex workers). However, little is known about the burden of HIV infection in transgender women worldwide. We aimed to better assess the relative HIV burden in all transgender women worldwide. Methods We did a systematic review and meta-analysis of studies that assessed HIV infection burdens in transgender women that were published between Jan 1, 2000, and Nov 30, 2011. Meta-analysis was completed with the Mantel-Haenszel method, and random-effects modelling was used to compare HIV burdens in transgender women with that in adults in the countries for which data were available. Findings Data were only available for countries with male-predominant HIV epidemics, which included the USA, six Asia-Pacific countries, five in Latin America, and three in Europe. The pooled HIV prevalence was 19·1% (95% CI 17·4–20·7) in 11 066 transgender women worldwide. In 7197 transgender women sampled in ten low-income and middle-income countries, HIV prevalence was 17·7% (95% CI 15·6–19·8). In 3869 transgender women sampled in five high-income countries, HIV prevalence was 21·6% (95% CI 18·8–24·3). The odds ratio for being infected with HIV in transgender women compared with all adults of reproductive age across the 15 countries was 48·8 (95% CI 21·2–76·3) and did not differ for those in low-income and middle-income countries compared with those in high-income countries. Interpretation Our findings suggest that transgender women are a very high burden population for HIV and are in urgent need of prevention, treatment, and care services. The meta-analysis showed remarkable consistency and severity of the HIV disease burden among transgender women. Funding Center for AIDS Research at Johns Hopkins and the Center for Public Health and Human Rights at the JHU Bloomberg School of Public Health.
1,142 citations
University College London1, University of Copenhagen2, University of St. Gallen3, University of Hamburg4, Hospital Clínico San Carlos5, University of Liverpool6, Universidad Miguel Hernández de Elche7, University of Victoria8, University of Zurich9, Karolinska University Hospital10, University of Bern11, Medical University of Vienna12, University Hospital of Basel13, Praxis14, Helsinki University Central Hospital15, Warwickshire Hospital16
TL;DR: Evaluating the rate of within-couple HIV transmission among serodifferent heterosexual and MSM couples during periods of sex without condoms and when the HIV-positive partner had HIV-1 RNA load less than 200 copies/mL found no phylogenetically linked transmissions.
Abstract: Importance A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex. Objective To evaluate the rate of within-couple HIV transmission (heterosexual and men who have sex with men [MSM]) during periods of sex without condoms and when the HIV-positive partner had HIV-1 RNA load less than 200 copies/mL. Design, Setting, and Participants The prospective, observational PARTNER (Partners of People on ART—A New Evaluation of the Risks) study was conducted at 75 clinical sites in 14 European countries and enrolled 1166 HIV serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex (September 2010 to May 2014). Eligibility criteria for inclusion of couple-years of follow-up were condomless sex and HIV-1 RNA load less than 200 copies/mL. Anonymized phylogenetic analysis compared couples’ HIV-1 polymerase and envelope sequences if an HIV-negative partner became infected to determine phylogenetically linked transmissions. Exposures Condomless sexual activity with an HIV-positive partner taking virally suppressive ART. Main Outcomes and Measures Risk of within-couple HIV transmission to the HIV-negative partner Results Among 1166 enrolled couples, 888 (mean age, 42 years [IQR, 35-48]; 548 heterosexual [61.7%] and 340 MSM [38.3%]) provided 1238 eligible couple-years of follow-up (median follow-up, 1.3 years [IQR, 0.8-2.0]). At baseline, couples reported condomless sex for a median of 2 years (IQR, 0.5-6.3). Condomless sex with other partners was reported by 108 HIV-negative MSM (33%) and 21 heterosexuals (4%). During follow-up, couples reported condomless sex a median of 37 times per year (IQR, 15-71), with MSM couples reporting approximately 22 000 condomless sex acts and heterosexuals approximately 36 000. Although 11 HIV-negative partners became HIV-positive (10 MSM; 1 heterosexual; 8 reported condomless sex with other partners), no phylogenetically linked transmissions occurred over eligible couple-years of follow-up, giving a rate of within-couple HIV transmission of zero, with an upper 95% confidence limit of 0.30/100 couple-years of follow-up. The upper 95% confidence limit for condomless anal sex was 0.71 per 100 couple-years of follow-up. Conclusions and Relevance Among serodifferent heterosexual and MSM couples in which the HIV-positive partner was using suppressive ART and who reported condomless sex, during median follow-up of 1.3 years per couple, there were no documented cases of within-couple HIV transmission (upper 95% confidence limit, 0.30/100 couple-years of follow-up). Additional longer-term follow-up is necessary to provide more precise estimates of risk.
1,039 citations
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TL;DR: The role of immune activation in the pathogenesis of non-AIDS clinical events (major causes of morbidity and mortality in people on antiretroviral therapy) is receiving increased recognition and breakthroughs in the prevention of HIV important to public health include male medical circumcision.
687 citations
References
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TL;DR: Infectivity for HIV through heterosexual transmission is low, and STDs may be the most important cofactor for transmission, and significant behavior change over time in serodiscordant couples was observed.
Abstract: 82 HIV-infected women and their male partners and 360 HIV-infected men and their female partners participated in a prospective study begun in 1985 to examine risk factors and rates of heterosexual transmission. Couples were recruited from health facilities in Northern California. The prospective phase of the study began in 1990 with physical examinations and interviews at 6-month interviews of serodiscordant couples who remained together. Couples were excluded if the non-index partner used injection drugs. Over 90% of participants were monogamous in the year preceding entry into the study. Median age was 33 for women and 35 for men. 66% of women and 68% of men were White and 18% of both sexes were Latino. 20% of index cases were injection drug users and 14% were infected through contaminated blood. 68 (19%) of the 360 female partners of male index cases and 2 (2.4%) of the 82 male partners of female index cases became infected. History of sexually transmitted diseases was the factor most strongly associated with transmission. The 3 other independent significant risk factors were anal sex having a partner infected through injected drug use and postcoital bleeding. The positive predictive value of risk factors was limited. Male-to-female transmission was approximately 8 times more efficient than female-to-male transmission. Male to female per-contact infectivity was estimated at 0.0009. No seroconversion was observed in the prospective study. Over time serodiscordant couples remaining in the study were more likely to use condoms or be abstinent and were less likely to practice anal intercourse.
360 citations
TL;DR: Estimates of the heterosexual infectivity of HIV-1 were very heterogeneous, ranging from zero transmissions after more than 100 penile-vaginal contacts in some serodiscordant couples to one transmission for every 3.1 episodes of heterosexual anal intercourse.
Abstract: Summary Studies of cumulative HIV incidence suggest that cofactors such as genital ulcer disease, HIV disease stage, and male circumcision influence HIV transmission; however, the heterosexual infectivity of HIV-1 is commonly cited as a fixed value (approximately 0·001, or one transmission per 1000 contacts). We sought to estimate transmission cofactor effects on the heterosexual infectivity of HIV-1 and to quantify the extent to which study methods have affected infectivity estimates. We undertook a systematic search (up to April 27, 2008) of PubMed, Web of Science, and relevant bibliographies to identify articles estimating the heterosexual infectivity of HIV-1. We used meta-regression and stratified random-effects meta-analysis to assess differences in infectivity associated with cofactors and study methods. Infectivity estimates were very heterogeneous, ranging from zero transmissions after more than 100 penile-vaginal contacts in some serodiscordant couples to one transmission for every 3·1 episodes of heterosexual anal intercourse. Estimates were only weakly associated with study methods. Infectivity differences, expressed as number of transmissions per 1000 contacts, were 8·1 (95 % CI 0·4–15·8) when comparing uncircumcised to circumcised susceptible men, 6·0 (3·3–8·8) comparing susceptible individuals with and without genital ulcer disease, 1·9 (0·9–2·8) comparing late-stage to mid-stage index cases, and 2·5 (0·2–4·9) comparing early-stage to mid-stage index cases. A single value for the heterosexual infectivity of HIV-1 fails to reflect the variation associated with important cofactors. The commonly cited value of 0·001 was estimated among stable couples with low prevalences of high-risk cofactors, and represents a lower bound. Cofactor effects are important to include in epidemic models, policy considerations, and prevention messages.
347 citations
TL;DR: Neither condom use, total number of sexual partners since 1978, nor lifetime number of sexually transmitted diseases was associated with infection.
Abstract: Ninety-seven female sexual partners of 93 men infected with human Immunodeficiency virus were studied. All of the women had sexual contact within the year before their partner had been diagnosed as having acquired Immunodeficiency syndrome or was found to have a positive reaction on the human immunodeficiency virus serologic test. Fifty-seven percent were the partners of bisexual men. Overall, 23% of the women were infected (95% confidence interval, 15% to 32%). The total number of exposures to the index case (sexual contacts with ejaculation) and the specific practice of anal intercourse, also with the infected partner, were associated with transmission. Neither condom use, total number of sexual partners since 1978, nor lifetime number of sexually transmitted diseases was associated with infection. ( JAMA 1987;258:788-790)
338 citations
TL;DR: This interpretation of the role of the primary infection is not conclusive, but its implications for prevention and for vaccine trials are so markedly different from those of other interpretations that it is considered to be an important hypothesis for further testing.
Abstract: A review of the data on infectivity per contact for transmission of the HIV suggests that the infectivity may be on the order of 0.1-0.3 per anal intercourse in the period of the initial infection, 10(-4) to 10(-3) in the long asymptomatic period, and 10(-3) to 10(-2) in the period leading into AIDS. The pattern of high contagiousness during the primary infection followed by a large drop in infectiousness may explain the pattern of epidemic spread seen in male homosexual cohorts in the early years of the epidemic. Simulations of cohorts of homosexual males, using that range of parameter values, indicate the following: (a) The initial fast rise and then more or less rapid flattening of the incidence curve of seropositives is primarily due to rapid initial spread, yielding a group of infecteds all of whom pass into the low infectivity asymptomatic period at close to the same time. All this occurs only if the basic reproduction number for the primary infection is > 1. (b) The behavioral changes that have been reported all started after the incidence of new infections began to fall, too late to have a major effect on the initial rise. The behavioral changes had a major effect in slowing down the subsequent rise in the number of seropositives. (c) High activity groups play an important role in the early rapid rise of the epidemic. However, it is not likely that the rapid decrease in rate of growth of seropositives is solely due to saturation of these very high activity groups. Although the evidence for this interpretation of the role of the primary infection is not conclusive, its implications for prevention and for vaccine trials are so markedly different from those of other interpretations that we consider it to be an important hypothesis for further testing.
335 citations
TL;DR: The analyses suggest that the risk of HIV transmission in heterosexual partnerships in the presence of effective treatment is low but non-zero and that the transmission risk in male homosexual partnerships is high over repeated exposures.
334 citations