Clinical trial NCT04050540: Doxycycline PEP for Prevention of Sexually Transmitted Infections Among Kenyan Women Using HIV PrEP
Official title: PrEP and dPEP: Doxycycline Post-exposure Prophylaxis for Prevention of Sexually Transmitted Infections Among Kenyan Women Using HIV Pre-exposure Prophylaxis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
HIV/AIDS
Neisseria Gonorrheae Infection
Chlamydia Trachomatis Infection
Syphilis Infection
Keywords: Sexually Transmitted Infections
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Kenya Medical Research Institute
name: Kenya National AIDS & STI Control Programme
name: University of California, San Francisco
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2019-08-08
Enrollment: 449
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a randomized clinical trial of doxycycline post-exposure prophylaxis (dPEP) to reduce bacterial STIs among Kenyan women taking pre-exposure prophylaxis (PrEP). The overarching goal is to assess the effectiveness of dPEP on incidence of STIs while also balancing acceptability, cost, and impact on tetracycline resistance to inform public health policy. Participants will be randomized to receive dPEP and standard of care or the standard of care only. Questionnaires, focus group discussions, SMS, and in-depth interviews will be used to study acceptability and changes sexual behavior due to dPEP.

Detailed description: This study is an open-label 1:1 randomized clinical trial of doxycyline PEP to reduce bacterial STIs - Neisseria gonorrhoeae, Chlamydia trachomatis, and T. pallidum (syphilis) - among Kenyan women taking PrEP. Participants will be counseled about the preliminary effectiveness data from IPERGAY, and the potential for resistance in STIs or other bacteria.

The primary study objectives are to 1) evaluate the effectiveness of doxycycline PEP (dPEP) to reduce STI infections in HIV-uninfected Kenyan women taking HIV PrEP; 2) assess the safety, tolerability, and acceptability of dPEP; 3)assess adherence to dPEP; 4) investigate the impact of dPEP on tetracycline resistance in N. gonorrhoeae and C. trachomatis; 5) measure the cost of dPEP and estimate the cost per case averted, budget impact, and affordability

Subjects will be randomized 1:1 to dPEP versus standard of care; randomization will be done in variable-sized blocks and using opaque envelopes opened at randomization. Participants assigned to dPEP will be instructed to take doxycycline 200 mg (two 100mg capsules) orally within 24 hours and up to 72 hours after each condomless sex act (consistent with IPERGAY) as frequently as daily if indicated but not more than once daily.

At Months 0,3,6 and 9, women randomized to dPEP will receive doxycycline, sufficient for up to daily use for 3 months (i.e., 180 capsules). Unused capsules will be counted at each quarterly follow-up visit and additional doxycycline will be provided. Participants will also be offered single- or multi-dose pill carriers for ease of dosing dPEP following exposures. All participants will receive quarterly visits for standard of care prevention services and collection of clinical and behavioral data, for a total of 12 months of follow-up.

Eligibility criteria: Inclusion Criteria:

* Willing and able to give written informed consent
* Age ≥18 years and ≤30 years old
* Female sex at birth
* HIV-seronegative at the time of last test within the past month and a current prescription for PrEP according to the national guidelines of Kenya (define PrEP eligibility as: partner of HIV-infected person not on ART or on ART for \<6 months, \>1 partner of unknown status, transactional sex, recent STI, recurrent HIV PEP use, inconsistent condom use, or injection drug use).

Exclusion Criteria:

* Pregnant
* Breastfeeding a child
* Allergy to tetracycline class
* Current medications which may impact doxycycline metabolism or that are contraindicated with doxycycline, as per the prescribing information. These include systemic retinoids, barbiturates, carbamazepine, phenytoin, and warfarin.
* Recent use of prolonged (more than 14 day course) antibiotics in the month prior to enrollment
* Active, clinically significant medical or psychiatric conditions that would interfere with study participation, at the discretion of the site investigator or designee.

Primary outcomes:
measure: Incidence of N. Gonorrhoeae, C. Trachomatis, or Early Syphilis Infection by Laboratory-based Diagnosis
timeFrame: 12 months post enrolment
Secondary outcomes:
Other outcomes:
Locations:
city: Kisumu
country: Kenya
facility: Kenya Medical Research Institute
Study officials:
affiliation: University of Washington
name: Jared Baeten, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stewart J, Bukusi E, Sesay FA, Oware K, Donnell D, Soge OO, Celum C, Odoyo J, Kwena ZA, Scoville CW, Violette LR, Morrison S, Simoni J, McClelland RS, Barnabas R, Gandhi M, Baeten JM. Doxycycline post-exposure prophylaxis for prevention of sexually transmitted infections among Kenyan women using HIV pre-exposure prophylaxis: study protocol for an open-label randomized trial. Trials. 2022 Jun 16;23(1):495. doi: 10.1186/s13063-022-06458-8.