Foreskin HIV Susceptibility Clinical Trial
Official title:
Testing the Ability of a Microbiome - Focused Intervention to Reduce HIV Susceptibility in Ugandan Men
This pilot study will assess the impact of four antimicrobial products (3 topical, one systemic) on the foreskin microbiome and HIV susceptibility of foreskin-derived CD4+ T cells. Participants will include HIV-uninfected Ugandan men presenting for elective male circumcision to reduce their HIV risk.
RATIONALE: The foreskin is the site of most HIV acquisition in uncircumcised heterosexual
men, and male circumcision (MC) reduces HIV risk by almost 60%. However, cultural and
practical barriers have led to suboptimal uptake. Foreskin inflammation, defined by elevated
levels of pro-inflammatory cytokines in the prepuce, is a key determinant of HIV acquisition
risk in uncircumcised men, and anaerobic bacteria within the foreskin microbiome may be an
important cause of this inflammation.
OBJECTIVES: A pilot in vivo - in vitro clinical study of four potential interventions to
reduce HIV susceptibility in the foreskin by altering the microbiome. The study is a
collaboration between the University of Toronto, IAVI-UVRI, and the Entebbe General Hospital.
We will recruit 125 men presenting for elective MC, along with regular female sexual partners
(if applicable). Participants will be randomized (n=25 per group) to immediate MC, or to one
of four intervention arms: twice-daily application of topical metronidazole 0.75%;
twice-daily application of topical clindamycin 2%; twice daily application of hydrogen
peroxide 1%; or oral tinidazole 2g once a day for two days. Swabs for immune and microbiome
studies will be collected before and after product. After 4 weeks the MC procedure will be
performed; foreskin CD4+ T cell susceptibility to HIV will be quantified using a flow
cytometry-based pseudovirus assay, and tissue immunohistochemistry performed. The primary and
secondary endpoints are outlined below. A secondary study will assess the impact of penile
topical antibiotic application on immunology and the microbiome in the genital tract of
female sexual partners.
OUTCOMES: This in vivo - in vitro clinical trial will define the causal role of the penile
microbiome in HIV susceptibility, and will assess potential strategies to take forward into
HIV efficacy trials in uncircumcised heterosexual men.
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