Penile barrier integrity and a mechanistic search for the effectiveness of medical male circumcision in preventing HIV acquisition

Title

Penile barrier integrity and a mechanistic search for the effectiveness of medical male circumcision in preventing HIV acquisition

Presenter

Cosnet Lerato Rametse

Authors

C.L. Rametse * (1), M.M. Mndini (1), Y. Ganief (1), O. Alinde (1), K. O'Hagan (1), R.L. Redondo (2), H.B. Jaspan (1), T.J. Hope (3), C.M. Gray (1)

Institutions

(1) University of Cape Town, Human Pathology, Cape Town, South Africa, (2) Northwestern University, Department of Medicine, Division of Infectious Disease & Immunology, Chicago, Illinois, United States, (3) Northwestern University, Cell & Molecular Biology, Chicago, United States

BACKGROUND: The biological mechanisms underlying HIV risk reduction following medical circumcision remain ill-defined. We sought to understand two aspects, whether circumcision can improve skin barrier integrity of the penis: in the absence and presence of an asymptomatic sexually transmitted infection (aSTI); the rationale being that changes in skin barrier integrity leads to lower risk of HIV susceptibility.
Objectives: We used hand-held meter devices to measure changes to skin barrier integrity in various sites on the penis of adults assigned male sex at birth. In vivo measurements of transepithelial water loss (TEWL) and skin hydration (proxies for barrier integrity) were taken directly on penile skin before and after MMC and in the absence/presence of an aSTI, the most common being Chlamydia trachomatis (approx. 11%).
METHODS: Vapometers and moisture meters SC, D and EpiD were used to measure TEWL (n=155) and dermal surface hydration (n=170) of the glans, inner foreskin and penile shaft before circumcision. Follow-up measurements were made at 2, 12 and 24 weeks after circumcision in the glans and shaft (n=16). Urines were collected for aSTI screening.
RESULTS: Compared to the shaft (16 g/hr/m² ), there was higher TEWL in the inner foreskin and glans in the absence of an aSTI (Medians of 27.6 and 22.3 g/hr/m²; both q<0,0001 respectively). Furthermore, the inner foreskin (Median 86,46 au) had increased hydration compared to the shaft (Median 54,61 au) q value<0,0001. Follow-up at six months after circumcision showed a significant decrease in TEWL in the glans (q=0.011) from the baseline, matching that of the shaft. Finally, prior to circumcision, the glans of participants with aSTI showed higher hydration compared to STI negative participants (97.4 vs 52.3 au; q= 0.0380).
CONCLUSIONS: Reduced TEWL after MMC in the glans without an aSTI suggests that skin barrier integrity increases after medical circumcision and may partly contribute to lower HIV-1 susceptibility. The higher glans skin moisture content in the presence of an aSTI before circumcision could create an infection-friendly niche and potentially lead to higher HIV-1 susceptibility.

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