Heterosexual Anal Intercourse: A Neglected Risk Factor for <scp>HIV</scp>?

Baggaley, Rebecca F.; Dimitrov, Dobromir; Owen, Branwen Nia; Pickles, Michael; Butler, Ailsa R.; Mâsse, Benoît; Boily, Marie‐Claude

doi:10.1111/aji.12064

Cited by 55 publications

(73 citation statements)

References 68 publications

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“…To assess the contribution of AI to transmission within heterosexual HIV and STI epidemics, information is required on frequency of heterosexual AI, with whom it is practised and whether it is condom protected [7]. Unfortunately, only 22 of 136 articles reported on condom use during AI and fewer still (N=13) reported on 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 frequency of AI, which is vital to understanding AI's contribution to HIV and other STI epidemics.…”

Section: Directions For Future Researchmentioning

confidence: 99%

“…This suggests that women may have an 18-fold higher HIV acquisition risk per UAI act compared to UVI. Even if a small fraction of all sex acts are UAI, AI may substantially contribute to HIV transmission and, at the population level, it may be as important as acute stage HIV (the first months following HIV infection, when infectivity is higher than during the asymptomatic stage) [5][6][7]. Intervention programmes that focus on reducing UAI may be easier to implement than those required to test and treat for recent infection, especially given the difficulties in identifying acute cases [5,7,8].…”

Section: Introductionmentioning

confidence: 99%

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Prevalence and Frequency of Heterosexual Anal Intercourse Among Young People: A Systematic Review and Meta-analysis

et al. 2015

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Abstract:We aim to assess if heterosexual anal intercourse (AI) is commonly practiced and how frequently it is practiced by young people.We searched PubMed for articles published 1975 to July 2014 reporting data on the proportion of young people (mean age <25) practicing heterosexual AI (AI prevalence) and on number of AI acts (AI frequency). Stratified random-effects meta-analysis and meta-regression were used to produce summary estimates and assess the influence of participant and study characteristics on AI prevalence.Eighty-three and thirteen of the 136 included articles reported data on lifetime AI prevalence and monthly AI frequency, respectively. Estimates were heterogenous. Overall summary estimates of lifetime AI prevalence were 22% (95% confidence interval (CI) 20-24%) among sexually active young people, with no statistically significant differences by gender, continent or age. Prevalence increased significantly with confidentiality of interview method and, among males and in Europe, by survey year. Prevalence did not significantly differ by recall period. An estimated 3-24% of all reported sex acts were AI.Reported heterosexual AI is common but variable among young people worldwide. To fully understand its impact on STI spread, more and better quality data on frequency of unprotected AI, and trends over time are required.

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Section: Directions For Future Researchmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prevalence and Frequency of Heterosexual Anal Intercourse Among Young People: A Systematic Review and Meta-analysis

et al. 2015

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“…However, several behavioral studies and clinical trial reports have shown that women also engage in unprotected receptive anal intercourse (RAI), with the highest rates of RAI being found among female sex workers and patients at sexually transmitted infection clinics (1)(2)(3)(4)(5)(6)(7)(8)(9). In addition, a recent metaanalysis demonstrated that the estimated per-act human immunodeficiency (HIV) transmission risk (per 10,000 exposures) for RAI is 138, compared to 11, 8, and 4 for insertive anal intercourse, receptive penile-vaginal intercourse, and insertive penile-vaginal intercourse, respectively (10).…”

mentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Evaluation following Vaginal Application of IQB3002, a Dual-Chamber Microbicide Gel Containing the Nonnucleoside Reverse Transcriptase Inhibitor IQP-0528 in Rhesus Macaques

Pereira¹,

Mesquita

Ham

et al. 2016

Antimicrob Agents Chemother

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fWe evaluated the in vivo pharmacokinetics and used a complementary ex vivo coculture assay to determine the pharmacodynamics of IQB3002 gel containing 1% IQP-0528, a nonnucleoside reverse transcriptase inhibitor (NNRTI), in rhesus macaques (RM). The gel (1.5 ml) was applied vaginally to 6 simian-human immunodeficiency (SHIV)-positive female RM. Blood, vaginal fluids, and rectal fluids were collected at 0, 1, 2, and 4 h. RM were euthanized at 4 h, and vaginal, cervical, rectal, and regional lymph node tissues were harvested. Anti-human immunodeficiency virus (HIV) activity was evaluated ex vivo by coculturing fresh or frozen vaginal tissues with activated human peripheral blood mononuclear cells (PBMCs) and measuring the p24 levels for 10 days after an HIV-1 Ba-L challenge. The median levels of IQP-0528, determined using liquid chromatography-tandem mass spectroscopy (LC-MS/MS) methods, were between 10 4 and 10 5 ng/g in vaginal and cervical tissue, between 10 3 and 10 4 ng/g in rectal tissues, and between 10 5 and 10 7 ng/ml in vaginal fluids over the 4-h period. The vaginal tissues protected the cocultured PBMCs from HIV-1 infection ex vivo, with a viral inhibition range of 81 to 100% in fresh and frozen tissues that were proximal, medial, and distal relative to the cervix. No viral inhibition was detected in untreated baseline tissues. Collectively, the median drug levels observed were 5 to 7 logs higher than the in vitro 50% effective concentration (EC 50 ) range (0.21 ng/ml to 1.29 ng/ml), suggesting that 1.5 ml of the gel delivers IQP-0528 throughout the RM vaginal compartment at levels that are highly inhibitory to HIV-1. Importantly, antiviral activity was observed in both fresh and frozen vaginal tissues, broadening the scope of the ex vivo coculture model for future NNRTI efficacy studies. HIV-1 microbicide clinical trials have primarily been focused on vaginal gels as a topical preexposure prophylaxis (PrEP) modality to prevent virus acquisition through vaginal intercourse in at-risk women. However, several behavioral studies and clinical trial reports have shown that women also engage in unprotected receptive anal intercourse (RAI), with the highest rates of RAI being found among female sex workers and patients at sexually transmitted infection clinics (1-9). In addition, a recent metaanalysis demonstrated that the estimated per-act human immunodeficiency (HIV) transmission risk (per 10,000 exposures) for RAI is 138, compared to 11, 8, and 4 for insertive anal intercourse, receptive penile-vaginal intercourse, and insertive penile-vaginal intercourse, respectively (10). The risk of HIV acquisition via unprotected RAI may be further exacerbated through the improper use of vaginal microbicide gels or high osmolality personal lubricants in the rectal compartment, which have been shown to cause cellular inflammation and epithelial damage (11-19). These studies collectively highlight a need for a microbicide formulation that is specifically designed for safe application in both the vaginal and rectal comp...

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“…Maintenance of each component is essential in protecting the body from luminal contents. The rectal mucosa is considered a susceptible site for human immunodeficiency virus (HIV) transmission, with characteristics that make this site particularly vulnerable including increased numbers of HIV target cells compared to those in other parts of the gastrointestinal tract and similar to those found in the vaginal tract, with the highest numbers of target cells at the distal rectum (4)(5)(6). Defects in rectal epithelial barrier integrity and function are a concern for increased risk of transmission (4,7), with growing concern that breaches in the epithelium may facilitate pathogen translocation (8) or stimulate an immune environment which facilitates transmission (7).…”

mentioning

confidence: 99%

In Vivo Rectal Mucosal Barrier Function Imaging in a Large-Animal Model by Using Confocal Endomicroscopy: Implications for Injury Assessment and Use in HIV Prevention Studies

Vargas

Vincent

Zhu

et al. 2016

Antimicrob Agents Chemother

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Injury occurring on the surface of the rectal mucosal lining that causes defects in barrier function may result in increased risk for transmission of infection by HIV and other pathogens. Such injury could occur from microbicidal or other topical agents, mechanical trauma during consensual or nonconsensual intercourse, or inflammatory conditions. Tools for evaluation of rectal mucosal barrier function for assessing the mucosa under these conditions are lacking, particularly those that can provide in vivo structural and functional barrier integrity assessment and are adaptable to longitudinal imaging. We investigated confocal endomicroscopy (CE) as a means for in vivo imaging of the rectal epithelial barrier in the ovine model following spatially confined injury to the surface at a controlled site using a topical application of the microbicide test agent benzalkonium chloride. Topical and intravenous (i.v.) fluorescent probes were used with CE to provide subcellular resolution imaging of the mucosal surface and assessment of barrier function loss. A 3-point CE grading system based on cellular structure integrity and leakage of dye through the mucosa showed significant differences in score between untreated (1.19 ؎ 0.53) and treated (2.55 ؎ 0.75) tissue (P < 0.0001). Histological grading confirmed findings of barrier compromise. The results indicate that CE is an effective means for detecting epithelial injury and barrier loss following localized trauma in a large-animal model. CE is promising for real-time rectal mucosal evaluation after injury or trauma or topical application of emerging biomedical prevention strategies designed to combat HIV.

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Heterosexual Anal Intercourse: A Neglected Risk Factor for HIV?

Cited by 55 publications

References 68 publications

Prevalence and Frequency of Heterosexual Anal Intercourse Among Young People: A Systematic Review and Meta-analysis

Prevalence and Frequency of Heterosexual Anal Intercourse Among Young People: A Systematic Review and Meta-analysis

Pharmacokinetic and Pharmacodynamic Evaluation following Vaginal Application of IQB3002, a Dual-Chamber Microbicide Gel Containing the Nonnucleoside Reverse Transcriptase Inhibitor IQP-0528 in Rhesus Macaques

In Vivo Rectal Mucosal Barrier Function Imaging in a Large-Animal Model by Using Confocal Endomicroscopy: Implications for Injury Assessment and Use in HIV Prevention Studies

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