Mayara Secco Torres da Silva1, Ronaldo Ismério Moreira1, Iuri Costa Leite1, Marcelo Cunha1, Thiago Silva Torres1, Carolina Coutinho1, Brenda Hoagland1, Marcos Benedetti1, Alessandro Farias2, Hamid Vega-Ramírez3, Kelika Konda4, Carlos F. Caceres4, Cristina Pimenta1, Valdiléa Gonçalves Veloso1, Beatriz Grinsztejn1

1 Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. 2 Centro Estadual Especializado em Diagnóstico, Assistência e Pesquisa (CEDAP) – Secretaria Estadual de Saúde – Salvador, Bahia, Brazil. 3 Instituto Nacional de Psiquiatria Ramon de la Fuente Muñiz, Mexico City, Mexico. 4 Universidad Peruana Cayetano Heredia, Lima, Peru.

 BACKGROUND

• Doxycycline post-exposure prophylaxis (doxy-PEP) is an effective strategy for STI prevention, with absent data from Latin America1.
• ImPrEP study evaluated same-day oral PrEP delivery for men who have sex with men (MSM) and transgender women (TGW) in Brazil, Mexico, and Peru. STI burden was high (31·7 cases per 100 person-years), with nearly one-third of participants accounting for all diagnoses2,3.
• While doxy-PEP efficacy is established, its optimal prescribing approach in real-world settings remains uncertain. In this analysis, we modeled and compared the potential impact, efficiency, and antibiotic consumption of alternative doxy-PEP prescribing approaches using ImPrEP data.

METHODS

1. ImPrEP participants were enrolled between 2018 and 2021, following the elegibility criteria: HIV-negative MSM and TGW aged older than 18 years, under high HIV vulnerability. For this analysis, we included only those with two or more STI assessments.
   1. Using observed STI diagnoses, (syphilis, chlamydia and gonorrhea), we modeled doxy-PEP use and averted STI diagnoses under three counterfactual prescribing strategies: (S1) initiation at baseline regardless of STI test;
   1. (S2) initiation after any positive STI test during follow-up;
   1. (S3) initiation after any positive STI test at baseline.
   1. Averted diagnoses were estimated by multiplying observed incidence by doxycycline efficacy from clinical trials.
   1. Strategy efficiency was assessed through the number needed to treat (NNT), defined as person-years of doxy-PEP use divided by diagnoses averted.
   1. Antibiotic consumption was expressed as monthly Defined Daily Doses (mDDD) per WHO standards, accounting for doxy-PEP use, estimated assuming an uptake of 75% and median use of 4 doses/person/month, and averted STI treatments

 RESULTS

• Of 7,529 participants included (95.4%: MSM; 70.9% non-white; median age: 29 years), 100% would receive doxy-PEP under S1, compared to 39.9% under S2 and 23% under S3. Among 3,795 observed incident STIs, S1 was projected to avert 77.6% of diagnoses versus 39.2% with S2 and 25.7% with S3. NNT was consistently higher in S1 than in S2 or S3 across all pathogens (Table).
• Estimated antibiotic consumption corresponded to a net increase of 22,185 mDDD in S1 compared to 8,721 mDDD in S2 and 5,053 mDDD in S3.

 CONCLUSIONS

1. In a population with high STI vulnerability, universal doxy-PEP under S1 could substantially reduce STI incidence but is associated with higher NNT and greater antibiotic consumption compared to S2 and S3.
2. Our results suggest that diagnosis-triggered strategies may offer a more efficient and rational approach to doxy-PEP use.
3. From a public health perspective, targeted initiation strategies may optimize impact while minimizing unnecessary antibiotic use, supporting more sustainable implementation of doxy-PEP in resource-constrained settings and antimicrobial resistance–sensitive contexts.