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: The history of HIV research in serodiscordant couples, the implications for management of couples, subsequent research on treatment as prevention in other key populations, and challenges in community implementation of these strategies are explored.
Abstract: The scientific breakthrough proving that antiretroviral therapy (ART) can halt heterosexual HIV transmission came in the form of a landmark clinical trial conducted among serodiscordant couples. Study findings immediately informed global recommendations for the use of treatment as prevention in serodiscordant couples. The extent to which these findings are generalizable to other key populations or to groups exposed to HIV through nonsexual transmission routes (i.e., anal intercourse or unsafe injection of drugs) has since driven a large body of research. This review explores the history of HIV research in serodiscordant couples, the implications for management of couples, subsequent research on treatment as prevention in other key populations, and challenges in community implementation of these strategies.
14 citations
TL;DR: In this article, the authors explored factors associated with casual unprotected anal intercourse (UAI) and travelling abroad among men who have sex with men (MSM) that were contracted abroad.
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TL;DR: All young people in northern Ugandan have been similarly affected by HIV infection during war and displacement, and post-conflict programme planners must abandon rudimentary targeting practices based on abductees as a high-profile category and develop evidence-based HIV interventions that are commensurate with young people’s specific needs.
Abstract: Thousands of former child soldiers who were abducted during the prolonged conflict in northern Uganda have returned to their home communities. Programmes that facilitate their successful reintegration continue to face a number of challenges. Although there is increasing knowledge of the dynamics of HIV infection during conflict, far less is known about its prevalence and implications for population health in the post-conflict period. This study investigated the effects of abduction on the prevalence of HIV and HIV-risk behaviours among young people in Gulu District, northern Uganda. An understanding of abduction experiences and HIV-risk behaviours is vital to both the development of effective reintegration programming for former child soldiers and the design of appropriate HIV prevention interventions for all young people. In 2010, we conducted a cross-sectional study of 2 sub-counties in Gulu District. A demographic and behavioural survey was interview-administered to a purposively selected sample of 384 transit camp residents aged 15–29. Biological specimens were collected for HIV rapid testing in the field and confirmatory laboratory testing. Descriptive statistics were used to describe characteristics of abduction. Additionally, a gender-stratified bivariate analysis compared abductees’ and non-abductees’ HIV risk profiles. Of the 384 participants, 107 (28%) were former child soldiers (61% were young men and 39% were young women). The median age of participants was 20 and median age at abduction was 13. HIV prevalence was similar among former abductees and non-abductees (12% vs. 13%; p = 0.824), with no differences observed by gender. With respect to differences in HIV vulnerability, our bivariate analysis identified greater risky sexual behaviours in the past year for former abductees than non-abductees, but there were no differences between the two groups’ survival/livelihood activities and food insufficiency experiences, both overall and by gender. The analysis further revealed that young northern Ugandans in general are in desperate need of education, skills development, and support for victims of sexual violence. This study persuasively demonstrates that all young people in northern Ugandan have been similarly affected by HIV infection during war and displacement. Post-conflict programme planners must therefore abandon rudimentary targeting practices based on abductees as a high-profile category. Instead, they must develop evidence-based HIV interventions that are commensurate with young people’s specific needs. As such programmes will be less stigmatizing, more oriented to self-selection, and more inclusive, they will effectively reach the most vulnerable young people in northern Uganda.
14 citations
Cites background from "HIV transmission risk through anal ..."
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TL;DR: Risk of infection is not zero but is low if the infected partner takes antiretrovirals, and the chance of infection being fatal if the partner takes anti-viral medication is low.
Abstract: Risk is not zero but is low if the infected partner takes antiretrovirals
Antiretroviral treatment inhibits HIV viral replication and reduces plasma viral load. Low plasma viral load is associated with a lower probability of HIV transmission, which opens the possibility of treatment to reduce HIV transmission.1 2 The feasibility, potential effectiveness, and risks of such treatment are unclear, and a key uncertainty is the extent to which successful antiretroviral treatment reduces HIV infectivity. In the linked observational study (doi:10.1136/bmj.c2205), Del Romero and colleagues estimate the risk of heterosexual transmission of HIV-1 from infected people taking combined antiretroviral treatment.3
Only randomised controlled trials comparing transmission in HIV serodiscordant couples, where the infected (index) partner receives or does not receive antiretroviral drugs, can accurately estimate the effect of such treatment on infectivity. The HPTN-052 trial is the only ongoing trial of this type. In this trial, partners infected with HIV are assigned to immediate antiretroviral treatment or deferred treatment when their CD4 count drops below 250 cells/μl. This trial will hopefully provide a good estimate of the effect of antiretroviral treatment in patients with more than 250 CD4 cells/μl, but it will obviously not obtain an estimate in patients with fewer than 250 CD4 cells/μl.
Evidence that …
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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
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