CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

1282 The Actual Need for DoxyPEP Might Not Be as Large as Expected

1283 Topical Doxycycline Inserts Show High Efficacy Against Vaginal Chlamydia Acquisition in Macaques David A. Garber 1 , M. Melissa Peet 2 , Hongwei Jia 1 , J. Harrison Priode 1 , James Mitchell 1 , Chuong Dinh 1 , Eric Edwards 1 , Richard Haaland 1 , Vivek Agrahari 2 , Meredith R. Clark 2 , S. Ajay Vishwanathan 1 , Janet McNicholl 1 , Gustavo F. Doncel 2 , Walid Heneine 1 , for the CDC Division of HIV Prevention CLIA Laboratory 1 Centers for Disease Control and Prevention, Atlanta, GA, USA, 2 Conrad-Eastern Virginia Medical School, Norfolk, VA, USA Background: Bacterial STIs are on the rise globally. Fast-dissolving dual-compartment (vaginal/rectal) inserts containing doxycycline (DOX) provide an alternate approach to STI prevention that can maximize local DOX concentrations while minimizing systemic distribution. Here, we performed preclinical studies to evaluate the pharmacokinetics (PK) and protective efficacy following vaginal administration of CONRAD-developed inserts containing DOX against vaginal C. trachomatis (CT) infection in pigtail macaques. Methods: Inserts were manufactured using a simple, easy-to-scale direct compression process containing 10 or 50mg DOX. DOX PK was determined via HPLC-tandem mass spectrometry analysis of vaginal swabs and plasma samples collected from macaques following vaginal administration of a 50mg or 10mg DOX insert. A physiologically-relevant challenge dose of 10 4 inclusion forming units (IFU) was identified for CT (serovar E) following a vaginal dose titration (10 6 -500 IFU). For efficacy studies, macaques were administered either a single vaginal insert containing DOX (50mg or 10mg), or no insert (Controls), at 4 hours (h) following vaginal challenge with 10 4 IFU CT. Animals were followed weekly, for 9 weeks, to monitor CT infection by testing vaginal swabs for the presence of CT rRNA via the Aptima Combo 2 target amplification assay. Macaques were considered to have an established CT infection if they exhibited Aptima positivity for 4 or more weeks following CT challenge. Results: Among macaques administered 10mg DOX inserts, DOX concentrations in vaginal secretions were high at 24h (279μg/ml) and persisted for at least 7 days at levels above DOX’s MIC 90 for CT (0.064μg/ml), whereas DOX was undetectable in plasma. All CT-challenged macaques that received inserts containing 50mg (N=4) or 10mg (N=4) DOX were protected, whereas 83% (5/6) controls became infected (P=0.048, each DOX group vs Controls). Conclusions: Vaginal delivery of DOX by inserts containing 10mg or 50mg DOX protected macaques against CT infection when administered 4h after CT challenge. Data provide the first evidence of a novel topical DOX modality for CT prevention. PK data demonstrated lack of systemic DOX distribution and highlight the role of sustained vaginal DOX in protection against CT. Findings inform the clinical development of DOX inserts for on-demand CT prevention and support DOX coformulation into tenofovir alafenamide and elvitegravir containing inserts, which are currently in clinical development for HIV prevention. 1284 Antimicrobial Consumption Among Users of Doxycycline Postexposure Prophylaxis in Milan, Italy Angelo Roberto Raccagni 1 , Sara Diotallevi 2 , Riccardo Lolatto 2 , Elena Bruzzesi 1 , Flavia Badalucco Ciotta 1 , Giacomo Ponta 1 , Flavia Passini 1 , Caterina Candela 1 , Camilla Muccini 2 , Antonella Castagna 2 , Silvia Nozza 1 1 San Raffaele Vita-Salute University, Milan, Italy, 2 IRCCS San Raffaele Scientific Institute, Milan, Italy Background: Aim is to evaluate the changes in antimicrobial consumption of ceftriaxone, benzylpenicillin and doxycycline for the treatment of bacterial sexually transmitted infections (bSTIs), after the prescription of doxycycline post-exposure prophylaxis (DoxyPEP) among men who have sex with men (MSM). Methods: Retrospective study of MSM in care for HIV or HIV pre-exposure prophylaxis (PrEP) at the Infectious Diseases Unit of San Raffaele Hospital, Milan, Italy, who received DoxyPEP counselling and prescription from August 2022 (first DoxyPEP prescription, baseline) to July 2024 (data lock). DoxyPEP was offered to people with ≥1 STI or reporting condomless sex with ≥1 partner. DoxyPEP with doxycycline 200mg within 72h of potential exposure was suggested for intensive sexual activity (>5 partners). All individuals with ≥1 follow-up visit after baseline and ≥1 before were included. DoxyPEP use was self-reported during routine visits. Individuals were tested for bSTIs (syphilis, Tp; chlamydia, Ct; gonorrhea, Ng) every 3-6 months according to local practice. Adjusted %change (and 95% confidence interval, CI) in incidence rate (IR) of STIs before and after DoxyPEP prescription were estimated using a pre-post within-person analysis by Poisson mixed-effects model. Use of DoxyPEP and ceftriaxone, benzylpenicillin, doxycycline for bSTIs treatment was quantified as

Roberto Rossotti 1 , Daniele Calzavara 2 , Enrico Caruso 2 , Anna De Bona 3 , Davide Moschese 4 , Camilla Muccini 5 , Daniele Tesoro 3 , Pietro Vinti 2 , Massimo Cernuschi 5 , Alessandro Tavelli 6 , Antonella d'Arminio Monforte 6 , Giuseppe Lapadula 7 1 ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy, 2 Milano Check Point, Milan, Italy, 3 ASST Santi Paolo e Carlo, Milan, Italy, 4 Luigi Sacco University Hospital, Milan, Italy, 5 IRCCS San Raffaele Scientific Institute, Milan, Italy, 6 Icona Foundation, Milan, Italy, 7 University of Milano–Bicocca, Milan, Italy Background: DoxyPEP proved to be effective in preventing bacterial sexually transmitted infections (STIs) and the Centers for Diseases Control and Prevention (CDC) recommended it in men who have sex with men (MSM) and transgender women (TGW) who have had at least one infection in the previous 12 months. However, the risk of antibiotic overuse and the potential spread of antimicrobial resistance led many scientific societies to issue more cautious and restrictive position statements. Aim of this study is to evaluate if CDC recommendations would be appropriate in a cohort of PrEP users assessing factors that describe individuals who might benefit most from doxyPEP. Methods: Milano Checkpoint is a community-based, peer-led service that provides medical assistance to one of the largest PrEP cohorts in Italy. Individuals who had at least one STI from July 2022 to June 2023 were selected. Demographic and behavioral features were collected. The diagnoses of syphilis, Chlamydia, and gonorrhea in the following 12 months were evaluated: potential antibiotic overuse was defined if no STIs were recorded during the follow up. Descriptive statistics were used to depict study population. Adjusted Poisson regression was used to describe variables associated to appropriate doxyPEP prescribing conditions (i.e., no antibiotic overuse). Results: The analysis included 251 individuals who had at least one STI in the previous year (90 Chlamydia, 83 gonorrhea, 26 syphilis, 52 had two or more infections). The majority was represented by men (97.6%), born in Italy (78.9%), white (85.6%), with a university degree (66.5%) (Table 1). During the follow up 129 STIs were registered (55 Chlamydia, 43 gonorrhea, 31 syphilis); 28 individuals (11.2%) had two or more infections. If doxyPEP had been taken, 85 (95%CI 70-98) infections would have been avoided. Nevertheless, 162 individuals (64.5%) had no further infections and would have had antibiotic overuse if they had taken doxyPEP. Adjusted Poisson regression found that the number of condomless intercourses was the only variable associated to an appropriate doxyPEP prescription (IRR 1.16 per 10 contacts, 95%CI 1.06-1.28, p=0.002). Conclusions: Our data suggest that CDC recommendations for doxyPEP prescription could be exceedingly broad leading to a considerable antibiotic overuse. Adding the evaluation of further behavioral variables could refine the selection of individuals who might benefit most from doxyPEP.

Poster Abstracts

CROI 2025 425