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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01 Jan 2017
TL;DR: This work charts a multicomponent prevention strategy with HIV positive gay men across four domains: improving HIV diagnosis and care continuum participation; enhancing risk reduction through counseling and treatment of comorbidities; engaging partner-related strategies; and mobilizing communities and structural interventions.
Abstract: HIV positive gay men have always been powerful advocates for HIV prevention and care. Renewed efforts to strengthen prevention with this group may benefit from the touchstone concepts of combination prevention and sexual health promotion. These concepts suggest that comprehensive HIV prevention should holistically promote the physical and mental health of HIV positive gay men, and must additionally extend to wider relationship, community, and policy contexts. We therefore chart a multicomponent prevention strategy with HIV positive gay men across four domains: improving HIV diagnosis and care continuum participation; enhancing risk reduction through counseling and treatment of comorbidities; engaging partner-related strategies; and mobilizing communities and structural interventions. Like a table with four legs, efforts to address prevention with HIV positive gay men will be unsteady without one or more of these components. Substantial gaps in the research evidence base for such an approach remain, and must be addressed.
1 citations
TL;DR: In this paper, the authors summarized the localized effects of HIV and dietary toxin aflatoxin B1 (AFB1), a common pollutant in high HIV burden regions, and evidence for pollutant-viral interactions.
Abstract: HIV transmission risk is dependent on the infectivity of the HIV+ partner and personal susceptibility risk factors of the HIV− partner. The mucosal barrier, as the internal gatekeeper between environment and self, concentrates and modulates the internalization of ingested pathogens and pollutants. In this review, we summarize the localized effects of HIV and dietary toxin aflatoxin B1 (AFB1), a common pollutant in high HIV burden regions, e.g., at the mucosal barrier, and evidence for pollutant-viral interactions. We compiled literature on HIV and AFB1 geographic occurrences, mechanisms of action, related co-exposures, personal risk factors, and HIV key determinants of health. AFB1 exposure and HIV sexual transmission hotspots geographically co-localize in many low-income countries. AFB1 distributes to sexual mucosal tissues generating inflammation, microbiome changes and a reduction of mucosal barrier integrity, effects that are risk factors for increasing HIV susceptibility. AFB1 exposure has a positive correlation to HIV viral load, a risk factor for increasing the infectivity of the HIV+ partner. The AFB1 exposure and metabolism generates inflammation that recruits HIV susceptible cells and generates chemokine/cytokine activation in tissues exposed to HIV. Although circumstantial, the available evidence makes a compelling case for studies of AFB1 exposure as a risk factor for HIV transmission, and a modifiable new component for combination HIV prevention efforts.
1 citations
TL;DR: In this article , the authors used two rheologically distinct suppositories in the vagina and rectum to evaluate the perception of the formulation properties of the suppositories and found significant differences and large Cohen's d effect sizes between vaginal and rectal experiences.
Abstract: Dual compartment suppositories are being developed to prevent HIV and other sexually transmitted infections. Such products, for use in the rectum, the vagina, or both, could have a significant public health impact by decreasing global incidence of these diseases. In this study, 16 women each used two rheologically distinct suppositories in their vagina and rectum. User Sensory Perception and Experience (USPE) scales assessed sensory experiences during sexual activity to understand whether, and how, women perceive formulation properties in the vagina and rectum. Qualitative data from individual in-depth interviews captured women's descriptions and comparisons of the experiences. Significant differences and large Cohen's d effect sizes between vaginal and rectal experiences of suppository-A were found for three scales: Application (APP): Product Awareness, SEX: Initial Penetration; and SEX: Effortful. Qualitative data provided user experience details that credibly align with these score differences. Near significant differences and large effect sizes were found for two additional scales: SEX: Perceived Wetness with suppository-A and SEX: Messiness with suppository-B. In addition, other scale scores showed medium-to-large effect sizes that correspond to hypothesized sensations associated with biophysical properties of the suppositories. Statistical significance combined with large effect sizes and qualitative data accurately represent the hypothesized perceptibility of suppository properties and identifies performance characteristics relevant to acceptability and adherence; together these data provide discernment of factors that can guide the development of dual compartment products. The Clinical Trial Registration number: NCT02744261.
1 citations
TL;DR: In this article , the authors optimized and tested tenofovir (TFV) and analog-based iso-osmolar (HOsm) rectal douches for efficacy against rectal simian/human immunodeficiency virus (SHIV) infection of macaques.
Abstract: In spite of the rollout of oral pre-exposure prophylaxis (PrEP), the rate of new HIV infections remains a major health crisis. In the United States, new infections occur predominantly in men having sex with men (MSM) in rural settings where access to PrEP can be limited. As an alternative congruent with MSM sexual behavior, we have optimized and tested tenofovir (TFV) and analog-based iso-osmolar and hypo-osmolar (HOsm) rectal douches for efficacy against rectal simian/human immunodeficiency virus (SHIV) infection of macaques. Single TFV HOsm high-dose douches achieved peak plasma TFV levels similar to daily oral PrEP, while other formulations yielded lower concentrations. Rectal tissue TFV-diphosphate (TFV-DP) concentrations at the portal of virus entry, however, were markedly higher after HOsm douching than daily oral PrEP. Repeated douches led to significantly higher plasma TFV and higher TFV-DP concentrations in rectal tissue at 24 hours compared with single douches, without detectable mucosal or systemic toxicity. Using stringent repeated intrarectal SHIV exposures, single HOsm high-dose douches delivered greater protection from virus acquisition for more than 24 hours compared with oral PrEP. Our results demonstrate a rapid delivery of protective TFV doses to the rectal portal of virus entry as a potential low-cost and safe PrEP alternative.
TL;DR: In this paper , the authors developed a methodology to identify small foci of transduced cells following rectal challenge of rhesus macaques with a non-replicative luciferase reporter virus.
Abstract: The study described herein is a continuation of our work in which we developed a methodology to identify small foci of transduced cells following rectal challenge of rhesus macaques with a non-replicative luciferase reporter virus. In the current study, the wild-type virus was added to the inoculation mix and twelve rhesus macaques were necropsied 2-4 days after the rectal challenge to study the changes in infected cell phenotype as the infection progressed. Relying on luciferase reporter we noted that both anus and rectum tissues are susceptible to the virus as early as 48h after the challenge. Small regions of the tissue containing luciferase-positive foci were further analyzed microscopically and were found to also contain cells infected by wild-type virus. Phenotypic analysis of the Env and Gag positive cells in these tissues revealed the virus can infect diverse cell populations, including but not limited to Th17 T cells, non Th17 T cells, immature dendritic cells, and myeloid-like cells. The proportions of the infected cell types, however, did not vary much during the first four days of infection when anus and rectum tissues were examined together. Nonetheless, when the same data was analyzed on a tissue-specific basis, we found significant changes in infected cell phenotypes over the course of infection. For anal tissue, a statistically significant increase in infection was observed for Th17 T cells and myeloid-like cells, while in the rectum, the non-Th17 T cells showed the biggest temporal increase, also of statistical significance. IMPORTANCE Men who have sex with men are at the highest risk of acquiring HIV via receptive anal intercourse. Understanding what sites are permissive to the virus, and what the early cellular targets are is critical for development of effective prevention strategies to control HIV acquisition amid receptive anal intercourse. Our work sheds light on the early HIV/SIV transmission events at the rectal mucosa by identifying the infected cells and highlights the distinct roles that different tissues play in virus acquisition and control.
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
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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 ...
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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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