Periodic presumptive treatment or doxycycline post-exposure prophylaxis for STI control among men who have sex with men in Indonesia (PRYSMA)

The World Health Organisation (WHO) has raised the alarm on the unprecedented increase in the global burden of bacterial sexually transmitted infections (STIs), which cause substantial morbidity and drive HIV transmission, particularly in low- and middle-income countries (LMIC). In Indonesia, the HIV and STI syndemic among men who have sex with men (MSM) and transgender women (TGW) is fuelled by underlying behavioural factors, socio-cultural stigma and structural barriers. Our MRC-funded INTERACT study (MR/V035304/1) found that 31.0% of MSM attending sexual health services in Jakarta and Bali had at least one STI, including chlamydia (21.7%), syphilis (18.0%) or gonorrhoea (13.3%). As in most LMIC, syndromic treatment is the standard-of-care, but this approach misses the majority of STIs because they are asymptomatic. To meet the 2030 WHO global targets for ending AIDS and reducing curable STIs, there is an urgent need for feasible, scalable and low-cost interventions to control STI, while awaiting technological advances. Doxycycline post-exposure prophylaxis (doxyPEP), a patient-controlled intervention, greatly reduced chlamydia and syphilis and variably reduced gonorrhoea, in three randomised trials among MSM in high-income settings. Periodic presumptive treatment (PPT) with azithromycin-cefixime, a provider-delivered intervention, has been recommended by WHO in 2011 to reduce asymptomatic chlamydia and gonorrhoea among MSM; several studies among female sex workers in Africa and Asia have shown good acceptance and reduced chlamydia and gonorrhoea, and variable reductions in syphilis. The potential benefits of implementing either doxyPEP or PPT for STI control among Asian MSM in LMIC are substantial. However, both strategies have yet to be tested in settings where syndromic treatment is standard-of-care, nucleic acid amplification testing for Neisseria gonorrhoeae and Chlamydia trachomatis is not routinely available, doxycycline-resistant NG is prevalent, and access to HIV pre-exposure prophylaxis (PrEP) is limited –as is the case for Indonesia. A big question mark hangs over the potential for AMR development that may arise from the real-world use of doxyPEP or PPT, both in Neisseria gonorrhoeae and medically important commensal bacteria, such as Staphylococcus aureus and Escherichia coli. Compared to doxyPEP, PPT has the potential advantage of reduced selection of antimicrobial-resistant strains due to possibly higher adherence (directly observed administration), a combination drug regimen, and substantially lower total antibiotic exposure. To assess the overall risk-benefit profile of doxyPEP and PPT, there is a strong rationale to conduct a randomized trial among MSM in LMIC. An open-label design comparing doxyPEP or PPT with standard-of-care syndromic treatment allows for optimal evaluation of effectiveness, acceptability, adherence and any changes in sexual practices or HIV risk. Set in MSM-friendly sexual health services in three major Indonesian cities, the PRYSMA trial strives to be an exemplary model for pragmatic, fit-for-purpose trials in underserved populations in LMIC, primarily driven by local research needs and co-created by community and policy stakeholders. To maximize the acceptability of the interventions, trial implementation will be integrated with social science, community-based participatory research and a tailored community engagement strategy. Our existing community advisory group will help build community trust and feedback, and align the research approach with community needs, based on the principle “nothing about us without us”. The project will convene a cross-sectoral stakeholder advisory group to guide policy translation. Ultimately, the proposed project envisions delivering a practice-defining trial with local and global relevance, contributing to meeting the 2030 global targets to ending AIDS and reducing curable STI.