Effect of Antibiotics on Penile Microbiome and HIV Susceptibility Study in Ugandan Men

University of Toronto

Status: Unknown

Conditions: Foreskin HIV Susceptibility

Treatments: Drug: Topical Clindamycin; Drug: Oral Tinidazole; Drug: Topical Hydrogen Peroxide; Drug: Topical metronidazole

Study type: Interventional

Funder types: Other

Identifiers

NCT03412071

Penile microbiome antibiotics

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 125 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Enrollment criteria include:

1. Aged 18 years or older
2. Biological male
3. Uncircumcised
4. HIV seronegative
5. Willing to comply with the requirements of the protocol
6. No current sexually transmitted infection (N. gonorrhoeae or C. trachomatis)
7. No clinically relevant genital symptoms / signs

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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125 participants in 5 patient groups

Control group

No Intervention group

Description:

25 HIV-uninfected, uncircumcised men will be immediately circumcised following enrollment. This group will serve as the comparison to the four intervention groups.

Oral tinidazole group

Active Comparator group

Description:

25 HIV-uninfected, uncircumcised men will be randomized to receive oral tinidazole 2g once a day for two days.

Treatment:

Drug: Oral Tinidazole

Topical metronidazole (0.75%) group

Active Comparator group

Description:

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.

Treatment:

Drug: Topical metronidazole

Topical clindamycin (2%) group

Active Comparator group

Description:

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.

Treatment:

Drug: Topical Clindamycin

Topical hydrogen peroxide (1%) group

Active Comparator group

Description:

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.

Treatment:

Drug: Topical Hydrogen Peroxide