Association between HIV and subpreputial penile wetness in uncircumcised men in South Africa.
ABSTRACT To describe the prevalence and characteristics of subpreputial penile wetness and to investigate the association between current levels of penile wetness and HIV infection.
Male attenders at a sexually transmitted infections clinic in Durban, South Africa were enrolled and treated for their presenting sexually transmitted infection complaint. They were asked to return after 14 days when a structured questionnaire was administered, and the degree of wetness of the glans penis and coronal sulcus was assessed clinically.
Six hundred and fifty men were enrolled, and 488 (75%) returned. Three hundred eighty-six uncircumcised men were included for statistical analysis of whom 215 (56%) were HIV positive. One hundred ninety-six (50.8%) had no penile wetness, and 190 (49.2%) had penile wetness. In the adjusted analysis, penile wetness was associated with younger age, low level of attained education, low income, higher lifetime numbers of sexual partners, and not washing after sex. The prevalence of HIV was greater in those with penile wetness 126 of 190 (66.3%) compared with 90 of 196 (45.9%) with no penile wetness, crude prevalence odds ratio 2.32 (95% confidence interval [CI], 1.54-3.50, P=or<0.001), crude prevalence relative risk 1.44 (95% CI, 1.23-1.63, P=or<0.001), and adjusted for predictors of HIV, confounders and herpes type 2 antibodies, odds ratio 2.38 (95% CI, 1.42-3.97, P=or<0.001), and relative risk 1.46 (95% CI, 1.19-1.68, P=or<0.001).
This is the first study to show an association between subpreputial penile wetness and HIV. Consideration should be given to providing advice about improving penile hygiene in uncircumcised men in areas where HIV is a significant problem. Good penile hygiene should also be promoted at the community level to become a desirable social norm.
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ABSTRACT: Male circumcision provides partial protection against multiple sexually transmitted infections (STIs), including HIV, but the mechanisms are not fully understood. To examine potential vulnerabilities in foreskin epithelial structure, we used Wilcoxon paired tests adjusted using the false discovery rate method to compare inner and outer foreskin samples from 20 healthy, sexually active Peruvian males who have sex with males or transgender females, ages 21-29, at elevated risk of HIV infection. No evidence of epithelial microtrauma was identified, as assessed by keratinocyte activation, fibronectin deposition, or parakeratosis. However, multiple suprabasal tight junction differences were identified: 1) inner foreskin stratum corneum was thinner than outer (p = 0.035); 2) claudin 1 had extended membrane-bound localization throughout inner epidermis stratum spinosum (p = 0.035); 3) membrane-bound claudin 4 was absent from inner foreskin stratum granulosum (p = 0.035); and 4) occludin had increased membrane deposition in inner foreskin stratum granulosum (p = 0.042) versus outer. Together, this suggests subclinical inflammation and paracellular transport modifications to the inner foreskin. A setting of inflammation was further supported by inner foreskin epithelial explant cultures secreting higher levels of GM-CSF (p = 0.029), IP-10 (p = 0.035) and RANTES (p = 0.022) than outer foreskin, and also containing an increased density of CCR5+ and CD4+ CCR5+ cells (p = 0.022). Inner foreskin dermis also secreted more RANTES than outer (p = 0.036), and had increased density of CCR5+ cells (p = 0.022). In conclusion, subclinical changes to the inner foreskin of sexually active males may support an inflammatory state, with availability of target cells for HIV infection and modifications to epidermal barriers, potentially explaining the benefits of circumcision for STI prevention.PLoS ONE 09/2014; 9(9):e108954. · 3.53 Impact Factor
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ABSTRACT: The 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.PLoS Pathogens 10/2014; 10(10):e1004416. · 8.14 Impact Factor
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ABSTRACT: Male circumcision (MC) has been shown to be protective against heterosexual HIV transmission and is being explored in some parts of the world as a means of combating the epidemic. The World Health Organization (WHO) recommends that MC be considered as an important component of HIV prevention in high prevalence settings. We review evidence that demonstrates that the inner foreskin is likely to be the main portal of entry for the HIV virus in males. Whether removal of the inner foreskin accounts for all the protection afforded by circumcision is yet to be established. The proposed mechanisms of protection range from inherent immunohistological factors of foreskin such as difference in thickness of keratin layer and density of target cells for HIV between inner and outer foreskin to physiological mechanisms that follow male circumcision such as drying of secretions underneath foreskin after sexual intercourse, loss of microbiome that attract target cells to the genital mucosa and lack of priming the genital mucosa with less abundant sexual transmitted infections among circumcised men. The aim of this review is to give an updated account on the mechanisms proposed so far on the demonstrated 50-70% protection from HIV transmission through heterosexual intercourse, by male circumcision.The Open AIDS Journal 09/2014; 8:31-44.