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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TL;DR: In this article, the authors performed a post-hoc analysis of the trial's data to investigate behavioural risk and efficacy every 6 months after vaccination, and found that the vaccine efficacy seemed to peak early and declined quickly.
Abstract: Summary Background The Thai phase 3 HIV vaccine trial RV 144 showed modest efficacy of a vaccine against HIV acquisition. Baseline variables of age, sex, marital status, and risk did not modify vaccine efficacy. We did a post-hoc analysis of the trial's data to investigate behavioural risk and efficacy every 6 months after vaccination. Methods RV 144 was a randomised, multicentre, double-blind, placebo-controlled efficacy trial testing the combination of the HIV vaccines ALVAC-HIV (vCP1521) and AIDSVAX B/E to prevent HIV infection or reduce setpoint viral load. Male and female volunteers aged 18–30 years were recruited from the community. In this post-hoc analysis of the modified intention-to-treat population (16 395 participants), HIV risk behaviour was assessed with a self-administered questionnaire at the time of initial vaccination in the trial and every 6 months thereafter for 3 years. We classified participants' behaviour as low, medium, or high risk. Both the acquisition endpoint and the early viral-load endpoint were examined for interactions with risk status over time and temporal effects after vaccination. Multiple proportional hazards regression models with treatment and time-varying risk covariates were analysed. Findings Risk of acquisition of HIV was low in each risk group, but 9187 (58·2%) participants reported higher-risk behaviour at least once during the study. Participants classified as high or increasing risk at least once during follow-up were compared with those who maintained low-risk or medium-risk behaviour as a time-varying covariate, and the interaction of risk status and acquisition efficacy was significant (p=0·01), with greater benefit in low-risk individuals. Vaccine efficacy seemed to peak early—cumulative vaccine efficacy was estimated to be 60·5% (95% CI 22–80) through the 12 months after initial vaccination—and declined quickly. Vaccination did not seem to affect viral load in either early or late infections. Interpretation Future HIV vaccine trials should recognise potential interactions between challenge intensity and risk heterogeneity in both population and treatment effects. The regimen tested in the RV 144 phase 3 trial might benefit from extended immunisation schedules. Funding US Army Medical Research and Materiel Command and Division of AIDS, National Institute of Allergy and Infectious Disease, National Institutes of Health.
185 citations
TL;DR: The updated British Association for Sexual Health and HIV (BASHH) guidelines for post-exposure prophylaxis (PEPSE) to HIV are presented and consideration is given to the place of PEPSE within the broader context of HIV prevention strategies and sexual health.
Abstract: We present the British Association for Sexual Health and HIV (BASHH) guidelines for post-exposure prophylaxis after sexual exposure (PEPSE) to HIV. This document includes a review of the current data to support the use of PEPSE, considers how to calculate the risks of HIV infection after a potential exposure, and provides recommendations on when PEPSE would and would not be considered. Other areas included are the possible impact on sexual behaviour, cost-effectiveness, and issues relating to service provision. Throughout the document, consideration is given to the place of PEPSE within the broader context of HIV prevention strategies and sexual health.
170 citations
TL;DR: Culturally-tailored programs that address economic disenfranchisement, increase engagement in care, screen for STIs, in conjunction with safer sex prevention interventions, may help to decrease further transmission in this heavily affected community.
Abstract: Background: American Black men who have sex with men (MSM) are disproportionately affected by HIV, but the factors associated with this concentrated epidemic are not fully understood. Methods: Black MSM were enrolled in 6 US cities to evaluate a multi-component prevention intervention, with the current analysis focusing on the correlates of being newly diagnosed with HIV compared to being HIV-uninfected or previously diagnosed with HIV. Results: HPTN 061 enrolled 1553 Black MSM whose median age was 40; 30% self-identified exclusively as gay or homosexual, 29% exclusively as bisexual, and 3% as transgender. About 1/6 th (16.2%) were previously diagnosed with HIV (PD); of 1263 participants without a prior HIV diagnosis 7.6% were newly diagnosed (ND). Compared to PD, ND Black MSM were younger (p,0.001); less likely to be living with a primary partner (p,0.001); more likely to be diagnosed with syphilis (p,0.001), rectal gonorrhea (p=0.011) or chlamydia (p=0.020). Compared to HIV-uninfected Black MSM, ND were more likely to report unprotected receptive anal intercourse (URAI) with a male partner in the last 6 months (p,0.001); and to be diagnosed with syphilis (p,0.001), rectal gonorrhea (p=0.004), and urethral (p=0.025) or rectal chlamydia (p,0.001). They were less likely to report female (p=0.002) or transgender partners (p=0.018). Multivariate logistic regression analyses found that ND Black MSM were significantly more likely than HIV-uninfected peers to be unemployed; have STIs, and engage in URAI. Almost half the men in each group were poor, had depressive symptoms, and expressed internalized homophobia. Conclusions: ND HIV-infected Black MSM were more likely to be unemployed, have bacterial STIs and engage in URAI than other Black MSM. Culturally-tailored programs that address economic disenfranchisement, increase engagement in care, screen for STIs, in conjunction with safer sex prevention interventions, may help to decrease further transmission in this heavily affected community.
164 citations
Cites result from "HIV transmission risk through anal ..."
...In order to obtain a sample of HIV-infected and uninfected Black MSM who were at increased risk for HIV acquisition or transmission, whether they were aware of their HIV status or not, enrollment of participants who were HIV-uninfected was capped at 200 participants at each site, and no more than 83 participants per site who refused HIV testing could be enrolled....
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...Although newly diagnosed Black MSM were less likely to report having HIV-infected partners than those were previously diagnosed or who were HIVuninfected, they reported having more unknown status partners than the other participants....
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...Conclusions: ND HIV-infected Black MSM were more likely to be unemployed, have bacterial STIs and engage in URAI than other Black MSM. Culturally-tailored programs that address economic disenfranchisement, increase engagement in care, screen for STIs, in conjunction with safer sex prevention interventions, may help to decrease further transmission in this heavily affected community....
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...Although levels of depressive symptoms and internalized homophobia did not differ between HIV-infected and uninfected Black MSM, they were very common, with 45% of the men in HPTN 061 reporting depressive symptomatology, and 43% noting increased levels of internalized homophobia....
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...These findings are consistent with other studies documenting high rates of HIV transmission in settings where HIV prevalence is high and a substantial number of men are unaware that they or their partners are HIV-infected [23,24]....
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TL;DR: A mathematical model is constructed to examine the impact and cost-effectiveness of different strategies, including earlier initiation of ART and/or PrEP, for HIV-1 prevention for serodiscordant couples.
Abstract: Background: Antiretrovirals have substantial promise for HIV-1 prevention, either as antiretroviral treatment (ART) for HIV-1–infected persons to reduce infectiousness, or as pre-exposure prophylaxis (PrEP) for HIV-1–uninfected persons to reduce the possibility of infection with HIV-1. HIV-1 serodiscordant couples in long-term partnerships (one member is infected and the other is uninfected) are a priority for prevention interventions. Earlier ART and PrEP might both reduce HIV1 transmission in this group, but the merits and synergies of these different approaches have not been analyzed. Methods and Findings: We constructed a mathematical model to examine the impact and cost-effectiveness of different strategies, including earlier initiation of ART and/or PrEP, for HIV-1 prevention for serodiscordant couples. Although the cost of PrEP is high, the cost per infection averted is significantly offset by future savings in lifelong treatment, especially among couples with multiple partners, low condom use, and a high risk of transmission. In some situations, highly effective PrEP could be cost-saving overall. To keep couples alive and without a new infection, providing PrEP to the uninfected partner could be at least as cost-effective as initiating ART earlier in the infected partner, if the annual cost of PrEP is ,40% of the annual cost of ART and PrEP is .70% effective. Conclusions: Strategic use of PrEP and ART could substantially and cost-effectively reduce HIV-1 transmission in HIV-1 serodiscordant couples. New and forthcoming data on the efficacy of PrEP, the cost of delivery of ART and PrEP, and couples behaviours and preferences will be critical for optimizing the use of antiretrovirals for HIV-1 prevention. Please see later in the article for the Editors’ Summary.
153 citations
TL;DR: Disparities in HIV transmission rates may be reduced by improving the HIV care continuum outcomes, but existing racial disparities in HIV prevalence will likely continue to drive higher incidence among black MSM for decades to come.
140 citations
References
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TL;DR: A new quantity is developed, I 2, which the authors believe gives a better measure of the consistency between trials in a meta-analysis, which is susceptible to the number of trials included in the meta- analysis.
Abstract: Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice?
Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis.
Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4
Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted?
A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …
45,105 citations
TL;DR: A checklist contains specifications for reporting of meta-analyses of observational studies in epidemiology, including background, search strategy, methods, results, discussion, and conclusion should improve the usefulness ofMeta-an analyses for authors, reviewers, editors, readers, and decision makers.
Abstract: ObjectiveBecause of the pressure for timely, informed decisions in public health
and clinical practice and the explosion of information in the scientific literature,
research results must be synthesized. Meta-analyses are increasingly used
to address this problem, and they often evaluate observational studies. A
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of meta-analyses of observational studies and to make recommendations to aid
authors, reviewers, editors, and readers.ParticipantsTwenty-seven participants were selected by a steering committee, based
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to other interested scientists. Funding for this activity was provided by
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attendees and additional experts. All suggestions for revisions were addressed.ConclusionsThe proposed checklist contains specifications for reporting of meta-analyses
of observational studies in epidemiology, including background, search strategy,
methods, results, discussion, and conclusion. Use of the checklist should
improve the usefulness of meta-analyses for authors, reviewers, editors, readers,
and decision makers. An evaluation plan is suggested and research areas are
explored.
17,663 citations
TL;DR: The problem of making a combined estimate has been discussed previously by Cochran and Yates and Cochran (1937) for agricultural experiments, and by Bliss (1952) for bioassays in different laboratories as discussed by the authors.
Abstract: When we are trying to make the best estimate of some quantity A that is available from the research conducted to date, the problem of combining results from different experiments is encountered. The problem is often troublesome, particularly if the individual estimates were made by different workers using different procedures. This paper discusses one of the simpler aspects of the problem, in which there is sufficient uniformity of experimental methods so that the ith experiment provides an estimate xi of u, and an estimate si of the standard error of xi . The experiments may be, for example, determinations of a physical or astronomical constant by different scientists, or bioassays carried out in different laboratories, or agricultural field experiments laid out in different parts of a region. The quantity xi may be a simple mean of the observations, as in a physical determination, or the difference between the means of two treatments, as in a comparative experiment, or a median lethal dose, or a regression coefficient. The problem of making a combined estimate has been discussed previously by Cochran (1937) and Yates and Cochran (1938) for agricultural experiments, and by Bliss (1952) for bioassays in different laboratories. The last two papers give recommendations for the practical worker. My purposes in treating the subject again are to discuss it in more general terms, to take account of some recent theoretical research, and, I hope, to bring the practical recommendations to the attention of some biologists who are not acquainted with the previous papers. The basic issue with which this paper deals is as follows. The simplest method of combining estimates made in a number of different experiments is to take the arithmetic mean of the estimates. If, however, the experiments vary in size, or appear to be of different precision, the investigator may wonder whether some kind of weighted meani would be more precise. This paper gives recommendations about the kinds of weighted mean that are appropriate, the situations in which they
4,335 citations
TL;DR: The viral load is the chief predictor of the risk of heterosexual transmission of HIV-1, and transmission is rare among persons with levels of less than 1500 copies of HIV -1 RNA per milliliter.
Abstract: Background and Methods We examined the influence of viral load in relation to other risk factors for the heterosexual transmission of human immunodeficiency virus type 1 (HIV-1). In a community-based study of 15,127 persons in a rural district of Uganda, we identified 415 couples in which one partner was HIV-1–positive and one was initially HIV-1–negative and followed them prospectively for up to 30 months. The incidence of HIV-1 infection per 100 person-years among the initially seronegative partners was examined in relation to behavioral and biologic variables. Results The male partner was HIV-1–positive in 228 couples, and the female partner was HIV-1–positive in 187 couples. Ninety of the 415 initially HIV-1–negative partners seroconverted (incidence, 11.8 per 100 person-years). The rate of male-to-female transmission was not significantly different from the rate of female-to-male transmission (12.0 per 100 person-years vs. 11.6 per 100 person-years). The incidence of seroconversion was highest among ...
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TL;DR: A theoretical strategy of universal voluntary HIV testing and immediate treatment with ART, combined with present prevention approaches, could have a major effect on severe generalised HIV/AIDS epidemics.
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