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: Pill-taking patterns may have a substantial impact on the protection provided by PrEP even when the same numbers of pills are taken, and can explain a broad range of efficacies observed in PrEP RCTs.
Abstract: Background Randomized controlled trials (RCTs) suggest that the efficacy of tenofovir-based preexposure prophylaxis (PrEP) strongly depends on the consistency of PrEP use. We explore how the patterns of pill taking and waning of PrEP protection may affect PrEP efficacy for HIV prevention. Methods A 2-arm RCT was simulated by mathematical models assuming that the prescribed daily doses were skipped periodically, randomly, or in large blocks. Risk-driven adherence, in which PrEP was taken when sex was expected, was also investigated. Three temporal PrEP protection profiles were explored: long (5 days), intermediate (3 days), and short (24 hours). Modeling results were compared to the efficacy observed in completed RCTs. Results The expected PrEP efficacy was 60% with periodic, 50% with random, and 34% with block adherence when PrEP had a long protection profile and pills were taken only 50% of the days. Risk-driven pill taking resulted in 29% and 37% daily pills taken and efficacy of 43% and 51%, respectively, for long protection. High PrEP efficacy comparable with that observed in Partners PrEP and Centers for Disease Control and Prevention Botswana trials was simulated under long protection, high overall adherence, and limited block pill taking; the moderate efficacy observed in iPrEx and Bangkok trials was comparable with the 50% adherence scenarios under random pill taking and long protection. Conclusions Pill-taking patterns may have a substantial impact on the protection provided by PrEP even when the same numbers of pills are taken. When PrEP retains protection for longer than a day, pill-taking patterns can explain a broad range of efficacies observed in PrEP RCTs.
33 citations
Cites background from "HIV transmission risk through anal ..."
...Anal intercourse was assumed to be 10 times riskier than vaginal intercourse with respect to HIV transmission.(16) The protective efficacy of male condoms against HIV was fixed at 90%....
[...]
TL;DR: In this paper, the relationship between gender-based discrimination and unprotected receptive anal intercourse (URAI) with stable partners among transgender women in Salvador, Brazil, was investigated through a cross-sectional survey conducted between 2014 and 2016.
Abstract: INTRODUCTION Discrimination related to gender identity may directly influence vulnerability to HIV through increased exposure to unprotected receptive anal intercourse (URAI). Little is known about the relationship between gender-based discrimination (GBD) and URAI with stable partners among transgender women. METHODS This mixed-methods research began with a cross-sectional survey conducted between 2014 and 2016 with transgender women in Salvador, the capital city in one of the poorest regions in Brazil. Respondent-driven sampling was used to recruit the study population. GBD was defined through Latent Class Analysis. Additionally, 19 semi-structured interviews with participants were transcribed and analyzed through thematic content analysis. RESULTS URAI with stable partners was commonly reported (37.3%). GDB was positively associated with URAI among stable partners (OR = 6.47; IC 95%: 1.67-25.02). The analysis of the interviews illustrated how GBD impacted transgender women in diverse ways. Experiences with GBD perpetrated by the family often initiated a trajectory of economic vulnerability that led many to engage in survival sex work. The constant experience with GBD contributed to participants feeling an immense sense of trust with their stable partners, ultimately diminished their desire to use condoms. Further, the high frequency of GBD contributed to poor mental health overall, though some participants said engagement in transgender advocacy efforts provided a vital source of resilience and support. CONCLUSION Our mixed-method study capitalizes upon the strengths of diverse data sets to produce a holistic understanding of GBD and URAI with stable partners. Furthermore, by confirming the association between greater GBD and URAI, we have demonstrated how GBD can impact condom negotiation in diverse relationships.
32 citations
TL;DR: Compared HIV RNA nucleic acid test results to the results of a 4th-generation Ag/Ab assay, the use of more sensitive assays, like NAT, in HIV screening of populations with a high prevalence of acute HIV infection is supported.
Abstract: Efforts to identify all persons infected with HIV in the United States are driven by the hope that early diagnosis will lower risk behaviors and decrease HIV transmission. Identification of HIV-infected people earlier in the course of their infection with HIV antigen/antibody (Ag/Ab) combination assays (4th-generation HIV assays) should help achieve this goal. We compared HIV RNA nucleic acid test (NAT) results to the results of a 4th-generation Ag/Ab assay (Architect HIV Ag/Ab Combo [HIV Combo] assay; Abbott Diagnostics) in 2,744 HIV antibody-negative samples. Fourteen people with acute HIV infection (HIV antibody negative/NAT positive) were identified; the HIV Combo assay detected nine of these individuals and was falsely negative in the remaining five. All five persons missed by the HIV Combo assay were in the stage of exponential increase in plasma virus associated with acute HIV infection (3, 7, 20, 35, 48). In contrast, most acutely infected persons detected by the HIV Combo assay demonstrated either a plateauing or decreasing plasma viral load. The HIV Combo assay also classified as positive five other samples which were negative by NAT. Taken together, the HIV Combo assay had a sensitivity of 73.7% and a specificity of 99.8%. Using published data, we estimated secondary transmission events had HIV infection in these five individuals remained undiagnosed. Screening of our population with NAT cost more than screening with the HIV Combo assay but achieved new diagnoses that we predict resulted in health care savings that far exceed screening costs. These findings support the use of more sensitive assays, like NAT, in HIV screening of populations with a high prevalence of acute HIV infection.
32 citations
Cites background from "HIV transmission risk through anal ..."
...025) to conservatively estimate potential secondary transmission events (1)....
[...]
TL;DR: Five annual cohorts of men who have sex with men attending New York City STD clinics who had negative HIV-1 nucleic acid amplification tests (NAATs) on the day of clinic visit have substantial HIV incidence and report risk behaviors that are highly associated with HIV acquisition.
Abstract: We examined five annual cohorts (2007-2011) of men who have sex with men (MSM) attending New York City STD clinics who had negative HIV-1 nucleic acid amplification tests (NAATs) on the day of clinic visit. Annual HIV incidence was calculated using HIV diagnoses within 1 year of negative NAAT, determined by matching with the citywide HIV registry. Predictors (demographic; behavioral; bacterial STD from citywide STD registry match) of all new HIV diagnoses through 2012 were calculated from Cox proportional hazards models. Among 10,487 HIV NAAT-negative MSM, 371 had an HIV diagnosis within 1 year. Annual incidence was 2.4/100 person-years, and highest among non-Hispanic black MSM (4.1/100 person-years) and MSM aged <20 years (5.7/100 person-years). Characteristics associated with all 648 new HIV diagnoses included: black race (aHR 2.2; 95 % CI 1.6-3.1), condomless receptive anal sex (aHR 2.1; 95 % CI 1.5-2.8), condomless insertive anal sex (aHR 1.3; 95 % CI 1.1-1.8), and incident STD diagnosis (aHR 1.6; 95 % CI 1.3-1.9). MSM attending STD clinics have substantial HIV incidence and report risk behaviors that are highly associated with HIV acquisition. Increased uptake of effective interventions, e.g., pre- and post-exposure prophylaxis, is needed.
32 citations
Additional excerpts
...However, we believe that our findings may well apply to other MSM populations, given the high per-act probability of HIV infection with receptive anal intercourse [28]....
[...]
TL;DR: Tenofovir gel is currently poised to move into Phase 2 evaluation and it is possible that a Phase 2B/3 effectiveness study with this product could be initiated in the next 2-3 years.
Abstract: The last few years have seen important progress in demonstrating the efficacy of oral pre-exposure prophylaxis, vaginal microbicides, and treatment as prevention as effective strategies for reducing the risk of acquiring or transmitting HIV infection. There has also been significant progress in the development of rectal microbicides. Preclinical non-human primate studies have demonstrated that antiretroviral microbicides can provide significant protection from rectal challenge with SIV or SHIV. Recent Phase 1 rectal microbicide studies have characterized the safety, acceptability, compartmental pharmacokinetics (PK), and pharmaco-dynamics (PD) of both UC781 and tenofovir gels. The tenofovir gel formulation used in vaginal studies was not well tolerated in the rectum and newer rectal-specific formulations have been developed and evaluated in Phase 1 studies. The PK/PD data generated in these Phase 1 studies may reduce the risk of advancing ineffective candidate rectal microbicides into late stage development. Tenofovir gel is currently poised to move into Phase 2 evaluation and it is possible that a Phase 2B/3 effectiveness study with this product could be initiated in the next 2–3 years.
32 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