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

Abstract

Background Women in Africa face disproportionate risk of human immunodeficiency virus (HIV) acquisition, accounting for more than half of new infections in Africa and similarly face a disproportionate burden of sexually transmitted infections (STIs). Very high STI prevalence is being observed globally, especially among people taking pre-exposure prophylaxis (PrEP) for HIV prevention. Doxycycline post-exposure prophylaxis (dPEP) has been proposed as an STI prevention strategy to reduce chlamydia, syphilis, and possibly gonorrhea, and trials are ongoing among cisgender men who have sex with men (MSM) and transgender women who are taking PrEP in high-income settings. We designed and describe here the first open-label trial to determine the effectiveness of dPEP to reduce STI incidence among cisgender women. Methods We are conducting an open-label 1:1 randomized trial of dPEP versus standard of care (STI screening and treatment and risk-reduction counseling without dPEP) among 446 Kenyan women aged ≥ 18 and ≤ 30 years old women taking PrEP. Women are followed for 12 months, with quarterly STI testing, treatment, and adherence counseling. The primary trial outcome will be the combined incidence of Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum, compared between the randomized groups. We will also assess dPEP acceptability, tolerability, safety, impact on sexual behavior, adherence, and occurrence of antimicrobial resistance (AMR) in N. gonorrhoeae and C. trachomatis isolates. Finally, we will estimate cost per incident STI case and complications averted accounting for nonadherence and benefits relative AMR or side effects. Discussion The results of this trial may have immediate implications for the global epidemic of STIs and sexual health. If effective, dPEP could put STI prevention into women’s hands. While dPEP may be able to prevent STIs, it carries important risks that could counter its benefits; global debate about the balance of these potential risks and benefits requires data to inform policy and implementation and our study aims to fill this gap. Trial registration ClinicalTrials.gov NCT04050540.

Position statement of the German STI Society on the prophylactic use of doxycycline to prevent STIs (Doxy‐PEP, Doxy‐PrEP)

“…These study participants either used HIV PrEP concurrently or had a known HIV infection. In contrast to the aforementioned studies, another randomized controlled study that included cisgender women in Kenya did not demonstrate effectiveness of antibiotic STI prevention in relation to Chlamydia trachomatis and Neisseria (N.) gonorrhoeae infections 19,20 …”

“…In contrast to the aforementioned studies, another randomized controlled study that included cisgender women in Kenya did not demonstrate effectiveness of antibiotic STI prevention in relation to Chlamydia trachomatis and Neisseria (N.) gonorrhoeae infections. 19,20 Differentiation from prophylactic treatment after exposure to confirmed syphilis It is important to differentiate antibiotic STI prevention from partner treatment after sexual contact with a person in whom early syphilis has been diagnostically confirmed. This approach is recommended in the current syphilis guidelines in Germany ("In the case of relevant pathogen contact, a prophylactic treatment should be offered analogous to the treatment of early syphilis", translation by the authors).…”

Acceptability and feasibility of leveraging community‐based HIV counselling and testing platforms for same‐day oral PrEP initiation among adolescent girls and young women in Eastern Cape, South Africa

“…Almost 90% of those young women and 59.0% of participants in this study were asymptomatic and would have been missed by WHO's syndromic management approach. It is essential to identify improved STI control strategies that are effective, affordable and put STI prevention into AGYW's hands [ 67 ]. Acceptable and feasible ways to identify and treat sexual partners are also needed to significantly improve reproductive health outcomes and impact of PrEP.…”

Predominance of High-Level Tetracycline-Resistant Neisseria gonorrhoeae in Kenya: Implications for Global Implementation of Doxycycline Postexposure Prophylaxis for Prevention of Sexually Transmitted Infections

“…12 Using archived endocervical swab specimens collected from 2008 and 2012 for STI testing in Kenya, 13,14 we evaluated the prevalence of tetracycline-resistant NG and CTamong cisgender women before launching a study of doxycycline PEP among cisgender women in Kenya. 15…”