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Journal ArticleDOI

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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Citations
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01 Jan 2015
TL;DR: In this article, the authors discuss the prevention of the heterosexual HIV infection among women, considering and relationship between this practice and their reproductive demands, based on a critical analysis of the recent literature on the issue.
Abstract: This article aims to discuss the prevention of the heterosexual HIV infection among women, considering and relationship between this practice and their reproductive demands, based on a critical analysis of the recent literature on the issue. It is assumed the relative exhaustion in the discourse about male condom use in all sexual relations, and the need to recognize that for many women in childbearing age, HIV prevention cannot be dissociated of the contraception practices, although the symbolic and technologically distinction between them. Furthermore, not always the contexts in which the sex occurs allows preventive practices. Women are different, and also their risks, vulnerabilities and needs, and this differences must be identified. The adequacy of preventive strategies to their particularities and situations experienced by each requires an effort of incorporation of available scientific knowledge to the actions taken by the health services, as well as conducting research on specific points relating to heterosexual practices.

1 citations

Dissertation
01 Mar 2017
TL;DR: This study suggests that AUD is linked to HIV risk in two important ways: first, through CLAI with non-stable partners and second, through amplifying the impact of other HIV risk behaviors.
Abstract: Substance Use, Sexual Networks, and HIV risk among men who have sex with men (MSM) and transgender women (TGW) in Peru Angela Kristine Ulrich Chair of the supervisory committee: Ann Duerr Affiliate Professor Epidemiology, Global Health Background: In Peru, the HIV epidemic is concentrated among men who have sex with men (MSM) and transgender women (TGW) in whom HIV incidence rates are as high as 4.2 per 100 person-years with HIV prevalence reported to be as high as 22% in MSM and up to 30% in TGW. This dissertation seeks to add to the knowledge of the structure of sexual networks, namely the level and predictors of sexual concurrency among MSM and TGW in Peru (Aim 1), and the understanding of risk factors for HIV acquisition in MSM and TGW with high levels of substance use in Lima (Aim 2). Methods: Data are from the 2011 Peruvian Biobehavioral Surveillance survey (Aim 1) and the Sabes cohort study conducted in Lima from 2013-2016 (Aim 2). Data were collected with the computer assisted self-interview (CASI) (Aim 1 & 2); HIV testing was performed with Determine 1/2 rapid antibody tests (Aim 1 & 2), pooled nucleic acid amplification test (NAAT), and Western Blot to determine Fiebig Stage at HIV diagnosis. Statistical methods used include Poisson regression and generalized estimating equations (GEE) (Aim 1), and Pearson’s Chi-square, Poisson regression estimated with GEE, and stratified Cox proportional hazards survival analysis with time-varying covariates (Aim 2). Results: Concurrency is a common practice among MSM and TGW in Peru with a 3-month cumulative prevalence of over 23%. There was evidence of negotiated safety—those with a stable partner were less likely to have condomless anal intercourse (CLAI) with a concurrent nonstable partner. In the Sabes cohort, HIV incidence was 11.7 per 100 person-years of follow-up. Those with alcohol use disorders (AUD) were significantly more likely to attend a venue that served alcohol, binge drink, and use marijuana or amyl nitrites. AUD modified the association between the time-varying behavioral factors and HIV; behavioral risk factors (binge drinking, marijuana use, sex with a casual partner, client, or one-time partner) were most strongly associated with HIV acquisition amongst those with dependent drinking patterns. Conclusion: This study suggests that AUD is linked to HIV risk in two important ways: first, through CLAI with non-stable partners and second, through amplifying the impact of other HIV risk behaviors. These studies suggest that harm reduction approaches, such as negotiated safety with concurrent partners, and treatment of AUDs to decrease alcohol intake could decrease the HIV risk associated with these behaviors. Table of

1 citations


Cites background from "HIV transmission risk through anal ..."

  • ...08%), it remains unclear whether sexual concurrency drives the epidemic in MSM and TGW populations or if these other factors are sufficient [17, 40]....

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DissertationDOI
06 Dec 2016
TL;DR: The results indicate that, regardless of subtype, the HIV-1 epidemic in Sao Paulo is selfsustained by treatment-naive MSM patients, who transmit the infection before starting treatment.
Abstract: Pimentel, VF. Study of genetic diversity of HIV inter and intra-host in recent infected patients. [Ph.D thesis (Microbiology)]. São Paulo: Instituto de Ciências Biomédicas, Universidade de São Paulo; 2016. The HIV-1 epidemic in Sao Paulo is changing, with a worrying increase in the number of new infections in young men and in the Men who have Sex with Men (MSM). The epidemic is dominated by subtypes B and F1, but there’s been a recent increase in the prevalence of subtype C. The aim of this study was to identify and characterize HIV-1 transmission networks in Sao Paulo, comparing across subtype epidemics, risk factors, and HAART exposure therapy. We gathered epidemiological, clinical and viral sequence data from HIV-1 infected individuals followed in Adolfo Lutz Institute/SP-BR from Jan 2004 through Feb 2015. After quality control, 2,260 sequences of the partial pol gene were subtyped as previously reported as B, C and F1 were included on this study. 2,107 unique background control sequences were selected by blasting our sequences against Los Alamos database and the Portuguese HIV-1 database. The dataset was screened for Drug Resistance Mutations to identify transmitted drug resistance mutations (TDRM). Maximum-Likelihood phylogenetic trees were built in RaxML for each subtype separately. We used Cluster Picker to analyze transmission dynamics according the thresholds: genetic distance (0.06) and bootstrap over 90%. Statistical analyzes were performed to identify possible correlates of clustering. Categorical variables were compared using Chi-square or Fisher’s exact test and quantitative variables were analyzed using Mann-Whitney test (SPSS). 414 (18,3%) of our population were included in clusters (range: 2-12 individuals). The rate of clustering did not differ between subtypes B and F, however more subtype C sequences (40%) significantly clustered together (p<0.001). Furthermore, more clusters were significantly found in the MSM group when compared to heterosexuals for all subtypes, (p<0.001). Also, drug naïve patients were more likely to be in clusters when compared to treated patients in all subtypes (p <0.001). TDRM were more prevalent in clustering than in non-clustering in subtypes B (p <0.001) and F1 (p =0.009), and more related to MSM group. Despite the higher number of clusters, subtype C presented a lower prevalence of TDRM, although without significant difference between cluster and non-cluster. Clustering individuals were also 5 years younger than non-clustering individuals for subtypes B and C (p<0.001 and 0.02, respectively). Our results indicate that, regardless of subtype, the HIV-1 epidemic in Sao Paulo is selfsustained by treatment-naive MSM patients, who transmit the infection before starting treatment. Subtype C presents a higher proportion of patients that cluster together. However, further analyses are necessary to clarify whether this implies a higher transmission rate of this subtype in Sao Paulo.

1 citations

Journal ArticleDOI
TL;DR: In this paper, the authors analyzed samples of MSM, PWID and HRH collected through the National HIV Behavioral Surveillance (NHBS) system in San Francisco to examine HIV risk taking and HIV burden to determine if the label "high-risk" is appropriately applied.
Abstract: HIV in the United States is concentrated in populations such as men who have sex with men (MSM), people who inject drugs (PWID), women of color and people living in poverty These populations are labeled high-risk for HIV infection because of the higher levels of HIV or HIV risk taking behaviors seen in these groups compared to other sub-populations It is also possible that a group may engage in behaviors that are "high-risk" for HIV infection but never become infected since HIV is not present or not present to a great extent in their social or sexual networks We analyzed samples of MSM, PWID and high-risk heterosexuals (HRH) collected through the National HIV Behavioral Surveillance (NHBS) system in San Francisco to examine HIV risk taking and HIV burden to determine if the label "high-risk" is appropriately applied NHBS samples MSM using time location sampling and PWID and HRH using Respondent Driven Sampling We sampled 508 MSM in 2011, 570 PWID in 2012 and 267 HRH in 2013 There were, as expected, differences in demographic characteristics across the three groups HRH had a greater number of high-risk behaviors compared to MSM and PWID but had the lowest HIV prevalence Focusing on risk behavior alone to label populations without considering the background HIV prevalence in communities, the types of risks engaged in and actual HIV infections may obscure which populations truly merit the label "high-risk" for HIV infection

1 citations

Dissertation
08 Feb 2012
TL;DR: The first phylogenetic model of immune escape that allows the codon substitution rates to depend on an arbitrary environmental parameter is developed and evolutionary models are developed and applied to study immune escape and drug resistance, and to predict epitopes.
Abstract: The rapidity with which the human immunodeficiency virus (HIV) adapts to its host environment presents huge challenges for the development of a fully protective vaccine. However, important insights have been gained from studying the characteristic footprints that the immune response and drug treatment leave on the virus. In this thesis, evolutionary models are developed and applied to study immune escape and drug resistance, and to predict epitopes. The first phylogenetic model of immune escape that allows the codon substitution rates to depend on an arbitrary environmental parameter is developed. The model is applied to identify sequence positions in an HIV Gag alignment that correlate with host human leukocyte antigen (HLA) genotypes across the phylogeny and which therefore provide evidence of escape from the cell-mediated immune response. T cell epitopes are then identified by combining this novel evolutionary model with a hidden Markov model that accounts for the sequence length and HLA binding motifs of known epitopes. This phylogenetic hidden Markov model is found to perform well in identifying documented T cell epitopes and can be combined with any other sequenceor structure-based epitope prediction tool to further enhance its performance. The model above is then extended to identify B cell epitopes based on the antibody neutralisation sensitivities of a panel of viruses. In particular, the model is adapted to allow the distribution of amino acids at each site to depend on neutralisation titre. Sites that influence neutralisation sensitivity across the phylogeny are identified by comparing the fit of this model to a null model in which the amino acids evolve independently of titre. The model is applied to a large panel of HIV envelope sequences with ID50 titres measured against the broadly neutralising sera of seven HIV-infected women. The predictions are shown to identify many amino acid positions that are known to be targeted by the antibodies in these and other broadly neutralising sera. Conformational B cell epitopes are successfully identified with a Markov chain Monte Carlo algorithm that searches the tertiary envelope structure for three-dimensional clusters of sites that influence neutralisation sensitivity. After considering HIV adaptation at the host population level, the focus then shifts to viral evolution within a host. The characteristics of transmitted viral variants are examined by analysing the breakthrough sequences from 96 monkeys experimentally infected with the simian immunodeficiency virus (SIV). It is shown that most infections are homogeneous and that the proportion of multiple founders is not significantly different for the animals that received a vaccine i ABSTRACT compared to those that did not, despite the vaccine having a significant protective effect against infection with one of the two challenge stocks. Sieve analyses are also performed to determine whether certain viral variants were selectively blocked from establishing infection by the vaccine-primed immune response. No evidence for such a sieve effect is found at the sequence, epitope or amino acid levels in this study. Finally, the population genetics parameters of HIV escape mutants within a host are estimated from longitudinal sequence data using maximum likelihood. The procedure is an extension of that of Bollback et al. [24], who assumed that mutants evolve according to the Wright-Fisher model. For computational reasons, this discrete model is commonly approximated by a diffusion process which assumes that selection and mutation are weak and is therefore inappropriate for modelling the evolution of HIV escape mutants. Here, the mutant frequency distribution is instead approximated by a Gaussian distribution with the mean and variance specified by a system of recurrence equations obtained with the δ method of statistics. Simulation studies are used to compare its performance to that of the standard diffusion approximation and the less well-known Gaussian diffusion approximation of Norman [275]. For large populations, the δ method is found to provide a much better approximation to the mutant frequency distribution when selection is strong, while all three methods perform comparably when selection is weak. Importantly, maximum likelihood estimates of the selection coefficient are severely attenuated when selection is strong under the two diffusion models, but not when the δ method is used. To demonstrate the utility of the approach, the method is applied to estimate the selection coefficient and effective population size of drug resistant mutants in temporal samples of next-generation HIV protease sequences.compared to those that did not, despite the vaccine having a significant protective effect against infection with one of the two challenge stocks. Sieve analyses are also performed to determine whether certain viral variants were selectively blocked from establishing infection by the vaccine-primed immune response. No evidence for such a sieve effect is found at the sequence, epitope or amino acid levels in this study. Finally, the population genetics parameters of HIV escape mutants within a host are estimated from longitudinal sequence data using maximum likelihood. The procedure is an extension of that of Bollback et al. [24], who assumed that mutants evolve according to the Wright-Fisher model. For computational reasons, this discrete model is commonly approximated by a diffusion process which assumes that selection and mutation are weak and is therefore inappropriate for modelling the evolution of HIV escape mutants. Here, the mutant frequency distribution is instead approximated by a Gaussian distribution with the mean and variance specified by a system of recurrence equations obtained with the δ method of statistics. Simulation studies are used to compare its performance to that of the standard diffusion approximation and the less well-known Gaussian diffusion approximation of Norman [275]. For large populations, the δ method is found to provide a much better approximation to the mutant frequency distribution when selection is strong, while all three methods perform comparably when selection is weak. Importantly, maximum likelihood estimates of the selection coefficient are severely attenuated when selection is strong under the two diffusion models, but not when the δ method is used. To demonstrate the utility of the approach, the method is applied to estimate the selection coefficient and effective population size of drug resistant mutants in temporal samples of next-generation HIV protease sequences.

1 citations

References
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Journal ArticleDOI
04 Sep 2003-BMJ
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

Journal ArticleDOI
19 Apr 2000-JAMA
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

Journal ArticleDOI
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

Journal ArticleDOI
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

Journal ArticleDOI
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

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