Doxycycline PEP for Prevention of Sexually Transmitted Infections Among Kenyan Women Using HIV PrEP

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.

• Doxycycline (Drug): 200 mg of doxycycline to be taken orally within 24 hours and up to 72 hours after each condomless sex act

Primary outcomes

• Incidence of N. Gonorrhoeae, C. Trachomatis, or Early Syphilis Infection by Laboratory-based Diagnosis [12 months post enrolment]: Combined incidence of N. gonorrhoeae, C. trachomatis, or early syphilis infection by by laboratory-based diagnosis (e.g., positive N. gonorrhoeae or C. trachomatis based on NAAT or syphilis based on four-fold increase in non-treponemal titers).

Sex: Female, ages: 18 Years to 30 Years, accepts healthy volunteers

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.

Participant flow

Outcome results

• Incidence of N. Gonorrhoeae, C. Trachomatis, or Early Syphilis Infection by Laboratory-based Diagnosis (Primary), Number, Events per 100 person-years: dPEP Intervention Arm 25.1; Standard of Care Arm 29.0

Adverse events

Time frame: 12 months

Other adverse events by term

• Results publication: Kwach B, Kwena Z, Violette LR, Rono B, Odoyo JB, Oware K, Bukusi EA, Baeten JM, Mkandawire-Valhmu L, Stewart J; dPEP Kenya Study Team. Understanding barriers and facilitators to doxycycline post-exposure prophylaxis adherence among young women in western kenya: a qualitative study. BMC Infect Dis. 2025 Jul 1;25(1):855. doi: 10.1186/s12879-025-11209-6. PMID 40597823
• Results publication: Stewart J, Oware K, Donnell D, Violette LR, Odoyo J, Soge OO, Scoville CW, Omollo V, Mogaka FO, Sesay FA, McClelland RS, Spinelli M, Gandhi M, Bukusi EA, Baeten JM; dPEP Kenya Study Team. Doxycycline Prophylaxis to Prevent Sexually Transmitted Infections in Women. N Engl J Med. 2023 Dec 21;389(25):2331-2340. doi: 10.1056/NEJMoa2304007. PMID 38118022
• Results publication: 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. PMID 35710444

• Study Protocol (PDF, 2021-05-04)
• Statistical Analysis Plan (PDF, 2022-10-24)

• Jared Baeten, MD, PhD, Principal investigator, University of Washington

NIH grants: R01AI145971