Title
Effect of Antibiotics on Penile Microbiome and HIV Susceptibility Study in Ugandan Men
Testing the Ability of a Microbiome - Focused Intervention to Reduce HIV Susceptibility in Ugandan Men
Phase
N/ALead Sponsor
University of TorontoStudy Type
InterventionalStatus
Unknown statusIndication/Condition
Foreskin HIV SusceptibilityIntervention/Treatment
Oral Tinidazole Topical metronidazole Topical Clindamycin Topical Hydrogen PeroxideStudy Participants
125This 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.
25 HIV-uninfected, uncircumcised men will be immediately circumcised following enrollment. This group will serve as the comparison to the four intervention groups.
25 HIV-uninfected, uncircumcised men will be randomized to receive oral tinidazole 2g once a day for two days.
25 HIV-uninfected, uncircumcised men will be randomized to apply topical 0.75% metronidazole cream to the foreskin twice a day for one week, and then twice a week for three weeks.
25 HIV-uninfected, uncircumcised men will be randomized to apply topical 2% clindamycin cream to the foreskin twice a day for one week, and then twice a week for three weeks.
25 HIV-uninfected, uncircumcised men will be randomized to apply 1% hydrogen peroxide cream to the foreskin twice a day for one week, and then twice a week for three weeks.
Enrollment criteria include: Aged 18 years or older Biological male Uncircumcised HIV seronegative Willing to comply with the requirements of the protocol No current sexually transmitted infection (N. gonorrhoeae or C. trachomatis) No clinically relevant genital symptoms / signs
