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Risk of HIV acquisition among circumcised and uncircumcised young men with penile human papillomavirus infection.

ABSTRACT: There are very few data from men on the risk of HIV acquisition associated with penile human papillomavirus (HPV) infection and no data on the potential modifying effect of male circumcision. Therefore, this study evaluated whether HPV is independently associated with risk of HIV.A cohort study of HPV natural history nested within a randomized control trial of male circumcision to reduce HIV incidence in Kisumu, Kenya.Prospective data from 2519 men were analyzed using 6-month discrete-time Cox models to determine if HIV acquisition was higher among circumcised or uncircumcised men with HPV compared to HPV-uninfected men.Risk of HIV acquisition was nonsignificantly increased among men with any HPV [adjusted hazard ratio (aHR) 1.72; 95% confidence interval (CI) 0.94-3.15] and high-risk HPV (aHR 1.92; 95% CI 0.96-3.87) compared to HPV-uninfected men, and estimates did not differ by circumcision status. Risk of HIV increased 27% with each additional HPV genotype infection (aHR 1.27; 95% CI 1.09-1.48). Men with persistent (aHR 3.27; 95% CI 1.59-6.72) or recently cleared (aHR 3.05; 95% CI 1.34-6.97) HPV had a higher risk of HIV acquisition than HPV-uninfected men.Consistent with the findings in women, HPV infection, clearance, and persistence were associated with an increased risk of HIV acquisition in men. Given the high prevalence of HPV in populations at risk of HIV, consideration of HPV in future HIV-prevention studies and investigation into mechanisms through which HPV might facilitate HIV acquisition are needed.

SUBMITTER: Rositch AF

PROVIDER: S-EPMC4074250 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Risk of HIV acquisition among circumcised and uncircumcised young men with penile human papillomavirus infection.

Rositch Anne F AF Mao Lu L Hudgens Michael G MG Moses Stephen S Agot Kawango K Backes Danielle M DM Nyagaya Edith E Snijders Peter J F PJ Meijer Chris J L M CJ Bailey Robert C RC Smith Jennifer S JS

AIDS (London, England) 20140301 5

<h4>Objectives</h4>There are very few data from men on the risk of HIV acquisition associated with penile human papillomavirus (HPV) infection and no data on the potential modifying effect of male circumcision. Therefore, this study evaluated whether HPV is independently associated with risk of HIV.<h4>Design</h4>A cohort study of HPV natural history nested within a randomized control trial of male circumcision to reduce HIV incidence in Kisumu, Kenya.<h4>Methods</h4>Prospective data from 2519 m ...[more]

PMID: 24149088

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Project description:BackgroundPenile coital injuries are one of the suggested mechanisms behind the increased risk of HIV among uncircumcised men. We evaluated the prevalence and correlates of self-reported penile coital injuries in a longitudinal community-based cohort of young (18-24 years old), newly circumcised and uncircumcised men in Western Kenya.MethodsSelf-reported penile coital injuries were assessed at baseline, 6, 12, 18 and 24 months of follow-up, and were defined as scratches, cuts or abrasions during sex, penile soreness during sex, and skin of the penis bleeding during sex. Associations between penile coital injuries, circumcision, sexual satisfaction, and other covariates were estimated with mixed effect models.ResultsBetween November 2008 and April 2010 3,186 participants were enrolled (1,588 into circumcision group and 1,598 as age-matched controls). Among 2,106 (66%) participants sexually active at baseline, 53% reported any penile injury, including 44% scratches, cuts or abrasions; 32% penile pain/soreness; and 22% penile bleeding. In multivariable modeling, risk was lower for circumcised men than uncircumcised men for scratches, cuts and abrasions (aOR = 0.39; 95% CI 0.34-0.44); penile pain/soreness (aOR = 0.58; 95% CI 0.51-0.65), penile bleeding (aOR = 0.53; 95% CI 0.46-0.62), and any penile coital injuries (aOR = 0.47; 95%CI 0.42-0.53). Other significant risk factors included increasing age, history of STIs and genital sores, and multiple sex partners, while condom use was protective. Coital injuries were significantly associated with lower levels of sexual satisfaction in longitudinal analyses (scratches, cuts or abrasions: aOR = 0.87, 95% CI: 0.76-0.98; penile pain/soreness: aOR = 0.82, 95% CI: 0.72-0.93; and penile bleeding: aOR = 0.65, 95% CI: 0.55-0.76).ConclusionsSelf-reported penile coital injuries were common and decreased significantly following circumcision. Improving sexual experience through the removal of a potential source of sexual discomfort may resonate with many men targeted for circumcision services. The role of penile coital injuries in sexual satisfaction, HIV, HSV-2, and as a motivator for seeking circumcision services should be explored further.

Project description:BACKGROUND:To date, the microbiota of the human penis has been studied mostly in connection with circumcision, HIV risk and female partner bacterial vaginosis (BV). These studies have shown that male circumcision reduces penile anaerobic bacteria, that greater abundance of penile anaerobic bacteria is correlated with increased cytokine levels and greater risk of HIV infection, and that the penile microbiota is an important harbour for BV-associated bacteria. While circumcision has been shown to significantly reduce the risk of acquiring human papillomavirus (HPV) infection, the relationship of the penile microbiota with HPV is still unknown. In this study, we examined the penile microbiota of HPV-infected men as well as the impact of HIV status. RESULTS:The penile skin microbiota of 238 men from Cape Town (South Africa) were profiled using Illumina sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene. Corynebacterium and Prevotella were found to be the most abundant genera. Six distinct community state types (CSTs) were identified. CST-1, dominated by Corynebacterium, corresponded to less infections with high-risk HPV (HR-HPV) relative to CSTs 2-6. Men in CST-5 had greater relative abundances of Prevotella, Clostridiales, and Porphyromonas and a lower relative abundance of Corynebacterium. Moreover, they were significantly more likely to have HPV or HR-HPV infections than men in CST-1. Using a machine learning approach, we identified greater relative abundances of the anaerobic BV-associated bacteria (Prevotella, Peptinophilus, and Dialister) and lower relative abundance of Corynebacterium in HR-HPV-infected men compared to HR-HPV-uninfected men. No association was observed between HIV and CST, although the penile microbiota of HIV-infected men had greater relative abundances of Staphylococcus compared to HIV-uninfected men. CONCLUSIONS:We found significant differences in the penile microbiota composition of men with and without HPV and HIV infections. HIV and HR-HPV infections were strongly associated with greater relative abundances of Staphylococcus and BV-associated bacterial taxa (notably Prevotella, Peptinophilus and Dialister), respectively. It is possible that these taxa could increase susceptibility to HIV and HR-HPV acquisition, in addition to creating conditions in which infections persist. Further longitudinal studies are required to establish causal relationships and to determine the extent of the effect.

Project description:Although male circumcision reduces the heterosexual HIV transmission risk, its effect may be attenuated if circumcised men increase sexual risk behaviours (SRB) due to perceived low risk. In Uganda information about the protective effects of circumcision has been publicly disseminated since 2007. If increased awareness of the protection increases SRB among circumcised men, it is likely that differences in prevalence of SRB among circumcised versus uncircumcised men will change over time. This study aimed at comparing SRBs and HIV sero-status of circumcised and uncircumcised men before and after the launch of the safe male circumcision programme.Data from the 2004 and 2011 Uganda AIDS Indicator Surveys (UAIS) were used. The analyses were based on generalized linear models, obtaining prevalence ratios (PR) as measures of association between circumcision status and multiple sexual partners, transactional sex, sex with non-marital partners, condom use at last non-marital sex, and HIV infection. In addition we conducted multivariate analyses adjusted for sociodemographic characteristics, and the multivariate models for HIV status were also adjusted for SRB.Twenty six percent of men were circumcised in 2004 and 28% in 2011. Prevalence of SRB was higher among circumcised men in both surveys. In the unadjusted analysis, circumcision was associated with having multiple sexual partners and non-marital partners. Condom use was not associated with circumcision in 2004, but in 2011 circumcised men were less likely to report condom use with the last non-marital partner. The associations between the other sexual risk behaviours and circumcision status were stable across the two surveys." In both surveys, circumcised men were less likely to be HIV positive (Adj PR 0.55; CI: 0.41-0.73 in 2004 and Adj PR 0.64; CI: 0.49-0.83 in 2011).There was higher prevalence of SRBs among circumcised men in both surveys, but the only significant change from 2004 to 2011 was a lower prevalence of condom use among the circumcised. Nevertheless, HIV prevalence was lower among circumcised men. Targeted messages for circumcised men and their sexual partners to continue using condoms even after circumcision should be enhanced to avoid risk compensation.

Project description:BackgroundThe foreskin is the site of most HIV acquisition in uncircumcised heterosexual men. Although HIV-exposed, seronegative (HESN) uncircumcised men demonstrate HIV-neutralizing IgA and increased antimicrobial peptides (AMPs) in the foreskin prepuce, no prospective studies have examined the mucosal immune correlates of HIV acquisition.MethodsTo assess the association of foreskin immune parameters with HIV acquisition, antimicrobial peptides and IgA with the capacity to neutralize a primary clade C HIV strain were quantified by blinded investigators, using sub-preputial swabs collected longitudinally during a randomized trial of male circumcision for HIV prevention in Rakai, Uganda.ResultsParticipants were 99 men who acquired HIV (cases) and 109 randomly selected controls who remained HIV seronegative. At enrollment, 44.4% of cases vs. 69.7% of controls demonstrated IgA neutralization (adjusted OR = 0.31; 95% CI, 0.16-0.61). IgA neutralization was detected in 38.7% of cases and 70.7% of controls at the last seronegative case visit prior to HIV acquisition and the comparable control visit (adjusted OR 0.21; 95% CI, 0.11-0.39). Levels of the α-defensins and secretory leukocyte protease inhibitor (SLPI) were over ten-fold higher in the foreskin prepuce of cases who acquired HIV, both at enrollment (mean 4.43 vs. 3.03 and 5.98 vs. 4.61 log(n) pg/mL, P = 0.005 and 0.009, respectively), and at the last seronegative visit (mean 4.81 vs. 3.15 and 6.46 vs. 5.20 log(n) pg/mL, P = 0.0002 and 0.013).ConclusionsThis prospective, blinded analysis is the first to assess the immune correlates of HIV acquisition in the foreskin. HIV-neutralizing IgA, previously associated with the HESN phenotype, was a biomarker of HIV protection, but other HESN associations correlated with increased HIV acquisition. This emphasizes the importance of prospective epidemiological studies or in vitro tissue studies to define the impact of mucosal parameters on HIV risk.

Dataset Information

Risk of HIV acquisition among circumcised and uncircumcised young men with penile human papillomavirus infection.

Publications

Risk of HIV acquisition among circumcised and uncircumcised young men with penile human papillomavirus infection.

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