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.
Citations
More filters
TL;DR: There is a limited amount of research in South Africa on HIV and non-normative gender identities and sexualities, especially WSW, lesbian, and/or bisexual female-identified populations, transgender populations, and LGB youth.
Abstract: Background:
The HIV epidemic in South Africa is characterized mainly by heterosexual transmission. Recently, the importance of targeting key populations and marginalized groups, including men who have sex with men (MSM) and transgender people, has been added to the national agenda.
26 citations
Cites background from "HIV transmission risk through anal ..."
...The high risk of infection is driven in part by frequently reported engagement in unprotected receptive anal intercourse with cisgender men [14, 57]....
[...]
TL;DR: PEG-PLGA NPs demonstrated to be safe carriers for rectal microbicide drug delivery and able to provide enhanced local PK that could be valuable in preventing rectal HIV transmission.
Abstract: Antiretroviral drug nanocarriers hold great promise for developing anti-human immunodeficiency virus (HIV) rectal microbicides However, challenges remain, namely, concerning which properties are more suited for enhancing colorectal distribution and retention of microbicide compounds In this work, we developed and assessed the in vitro and in vivo performance of poly(lactic- co-glycolic acid) (PLGA)-based nanoparticles (NPs) as carriers for the model drug efavirenz (EFV) We particularly focused on the effect of noncovalent poly(ethylene glycol) coating of PLGA NPs (PEG-PLGA NPs) conferring a mucus-diffusive behavior on the pharmacokinetics (PK) of EFV following rectal administration to mice Drug-loaded PLGA NPs and PEG-PLGA NPs (200-225 nm) were obtained by nanoprecipitation Both types of systems were able to retain native antiretroviral activity of EFV in vitro, while featuring lower cytotoxicity against different epithelial cell lines and HIV target cells Also, PLGA NPs and PEG-PLGA NPs were readily taken up by colorectal cell lines and mildly reduced EFV permeation while increasing membrane retention in Caco-2 and Caco-2/HT29-MTX cell monolayer models When administered intrarectally to CD-1 mice in phosphate-buffered saline (pH 74), EFV-loaded PEG-PLGA NPs consistently provided higher drug levels in colorectal tissues and lavages, as compared to free EFV or drug-loaded PLGA NPs Mean values for the area-under-the-curve between 15 min and 12 h following administration were particularly higher for PEG-PLGA NPs in distal and middle colorectal tissues, with relative bioavailability values of 37 and 29, respectively, as compared to free EFV (22 and 60 over PLGA NPs, respectively) Systemic exposure to EFV was reduced for all treatments NPs were further shown safe after once-daily administration for 14 days, as assessed by histological analysis of colorectal tissues and chemokine/cytokine assay of rectal lavages Overall, PEG-PLGA NPs demonstrated to be safe carriers for rectal microbicide drug delivery and able to provide enhanced local PK that could be valuable in preventing rectal HIV transmission
26 citations
TL;DR: Widening the cascade with a preventive extension, including pre-exposure prophylaxis, the first proven efficacious and only biomedical HIV prevention strategy in MSM, will be instrumental in achieving HIV epidemic control in this group.
Abstract: In Asia Pacific, most countries have expanded HIV treatment guidelines to include all those with HIV infection and adopted antiretroviral treatment for prevention (TFP) as a blanket strategy for HIV control. Although the overall epidemic development associated with this focus is positive, the HIV epidemic in men who have sex with men (MSM) is continuing unperturbed without any signs of decline or reversal. This raises doubt about whether TFP as a blanket HIV prevention policy is the right approach. This paper reviews currently available biomedical HIV prevention strategies, national HIV prevention policies and guidelines from selected countries and published data on the HIV cascade in MSM. No evidence for efficacy of TFP in protecting MSM from HIV infection was found. The rationale for this approach is based on assumptions about biological plausibility and external validity of latency-based efficacy found in heterosexual couples. This is different from the route and timing of HIV transmission in MSM. New HIV infections in MSM principally occur in chains of acutely HIV-infected highly sexually active young men, in whom acquisition and transmission are correlated in space and time. By the time TFP renders its effects, most new HIV infections in MSM will have already occurred. On a global level, less than 6% of all reports regarding the HIV care cascade from 1990 to 2016 included MSM, and only 2.3% concerned MSM in low/middle-income countries. Only one report originated from Asia Pacific. Generally, HIV cascade data in MSM show a sobering picture of TFP in engaging and retaining MSM along the continuum. Widening the cascade with a preventive extension, including pre-exposure prophylaxis, the first proven efficacious and only biomedical HIV prevention strategy in MSM, will be instrumental in achieving HIV epidemic control in this group.
26 citations
TL;DR: Health programming for men who have sex with men in South Africa has been ignored or absent until fairly recently, despite this population being at high risk for HIV acquisition and transmission.
Abstract: Health programming for men who have sex with men (MSM) in South Africa has been ignored or absent until fairly recently, despite this population being at high risk for HIV acquisition and transmission. Anova Health Institute, with support from the US President's Emergency Plan for AIDS Relief (PEPFAR)/United States Agency for International Development (USAID) and in collaboration with the South African National Department of Health, launched the first state sector MSM-targeted sexual health clinic in 2010. The clinic has been successful in attracting and retaining MSM in care, and lessons learned are described in this article. Components contributing to the creation of MSM-appropriate healthcare services are discussed.
26 citations
Cites background from "HIV transmission risk through anal ..."
...[7] This is due to the friable nature of the rectal mucosa, which does not contain mucous-producing cells like the thicker, selflubricating lining of the vagina....
[...]
TL;DR: HIV prevention interventions should target MSM with early homosexual debut and psychosocial health problems, while HIV/AIDS education among MSM should focus on increasing knowledge of HIV risk, estimated HIV prevalence and antiretroviral therapy, and improving risk perception of HIV acquisition.
Abstract: Men who have sex with men (MSM) are a large high-risk population for HIV infection in recent years in China. A cross-sectional survey was conducted in Hangzhou, China, to determine rates of condomless anal intercourse (CAI), recent HIV testing (in the recent year) and associated factors using respondent-driven sampling. Questionnaires using face-to-face interviews were employed to collect data on sexual risk behaviors and HIV testing. Five hundred eleven MSM were recruited, of which 459 (89.8%) had anal intercourse in the past 6 months. Of these 459 participants, 457 (99.6%) answered whether they had taken an HIV test in the recent year, so only their data were analyzed. Weighted data were analyzed using bivariate and multivariate logistic regression analysis. The CAI rate with male partners in the past 6 months was 43.7% (95% confidence interval [CI], 34.0-51.5%), while the rate of condomless vaginal intercourse (CVI) was 21.6% (95% CI, 15.6-32.3%). The prevalence of recent HIV testing was 56.8% (95% CI, 48.7-66.5%), while the prevalence of HIV and syphilis were 8.8% and 6.5%, respectively. Multivariate analysis indicated that CAI was associated with earlier homosexual debut, suicidal inclinations, childhood sexual abuse, HIV testing in the recent year, and lower estimate of HIV prevalence. Recent HIV testing was associated with homosexual debut age, engaging in CAI with male partners in the past 6 months, having oral sex in the past 6 months, self-perceived higher likelihood of HIV infection, knowing about antiretroviral therapy for HIV/AIDS, receiving AIDS/sexually transmitted infection (STI) interventions in the past year, and syphilis infection. Given high prevalence of HIV and syphilis, high levels of CAI and CVI, and low HIV testing rate, the results indicated high risk of HIV infection and transmission among MSM. HIV prevention interventions should target MSM with early homosexual debut and psychosocial health problems, while HIV/AIDS education among MSM should focus on increasing knowledge of HIV risk, estimated HIV prevalence and antiretroviral therapy, and improving risk perception of HIV acquisition.
26 citations
References
More filters
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
workshop was held in Atlanta, Ga, in April 1997, to examine the reporting
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
on expertise in clinical practice, trials, statistics, epidemiology, social
sciences, and biomedical editing. Deliberations of the workshop were open
to other interested scientists. Funding for this activity was provided by
the Centers for Disease Control and Prevention.EvidenceWe conducted a systematic review of the published literature on the
conduct and reporting of meta-analyses in observational studies using MEDLINE,
Educational Research Information Center (ERIC), PsycLIT, and the Current Index
to Statistics. We also examined reference lists of the 32 studies retrieved
and contacted experts in the field. Participants were assigned to small-group
discussions on the subjects of bias, searching and abstracting, heterogeneity,
study categorization, and statistical methods.Consensus ProcessFrom the material presented at the workshop, the authors developed a
checklist summarizing recommendations for reporting meta-analyses of observational
studies. The checklist and supporting evidence were circulated to all conference
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 ...
2,897 citations
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.
1,948 citations