CDC Clinical Guidelines on the Use of Doxycycline Postexposure Prophylaxis for Bacterial Sexually Transmitted Infection Prevention, United States, 2024.

No vaccines and few chemoprophylaxis options exist for the prevention of bacterial sexually transmitted infections (STIs) (specifically syphilis, chlamydia, and gonorrhea). These infections have increased in the United States and disproportionately affect gay, bisexual, and other men who have sex with men (MSM) and transgender women (TGW). In three large randomized controlled trials, 200 mg of doxycycline taken within 72 hours after sex has been shown to reduce syphilis and chlamydia infections by >70% and gonococcal infections by approximately 50%. This report outlines CDC's recommendation for the use of doxycycline postexposure prophylaxis (doxy PEP), a novel, ongoing, patient-managed biomedical STI prevention strategy for a selected population. CDC recommends that MSM and TGW who have had a bacterial STI (specifically syphilis, chlamydia, or gonorrhea) diagnosed in the past 12 months should receive counseling that doxy PEP can be used as postexposure prophylaxis to prevent these infections. Following shared decision-making with their provider, CDC recommends that providers offer persons in this group a prescription for doxy PEP to be self-administered within 72 hours after having oral, vaginal, or anal sex. The recommended dose of doxy PEP is 200 mg and should not exceed a maximum dose of 200 mg every 24 hours.Doxy PEP, when offered, should be implemented in the context of a comprehensive sexual health approach, including risk reduction counseling, STI screening and treatment, recommended vaccination and linkage to HIV PrEP, HIV care, or other services as appropriate. Persons who are prescribed doxy PEP should undergo bacterial STI testing at anatomic sites of exposure at baseline and every 3-6 months thereafter. Ongoing need for doxy PEP should be assessed every 3-6 months as well. HIV screening should be performed for HIV-negative MSM and TGW according to current recommendations.

Perceptions about doxycycline post-exposure prophylaxis (Doxy-PEP) as an STI-prevention strategy among gay and bisexual men (GBM) in the United States: Results from a qualitative study.

OBJECTIVE: To leverage qualitative data to explore gay and bisexual men's (GBM) perceptions about doxycycline post-exposure prophylaxis (Doxy-PEP). Doxy-PEP is a novel biomedical STI-prevention strategy that helps reduce the risk of acquiring bacterial STIs. Little is known about Doxy-PEP's acceptability in the U.S., nor how best to engage those most vulnerable to STIs in taking up this nascent prevention strategy. METHOD: Between July and September of 2023, 24 GBM from across the U.S. completed qualitative interviews about their perceptions regarding Doxy-PEP. Interviews were analyzed using a codebook approach to thematic analysis. RESULTS: Participants were generally interested in using Doxy-PEP, but were concerned about the potential for antibiotic resistance, side-effects, medication interactions to occur, along with stigmatizing discourse around its use. Meanwhile, participants were motivated by the simplicity of Doxy-PEP and the protection it could confer on both an individual and community-level- as well as its potential to reduce STI-related anxiety. Finally, participants desired additional information on Doxy-PEP to address their concerns. CONCLUSIONS: There is a need for clear guidelines and expanded public health messaging on Doxy-PEP in the U.S.

Rabies death in an adolescent tribal girl diagnosed postmortem, in Kerala - the precious life, preventable loss and equity concerns.

BACKGROUND: Rabies is a neglected tropical disease endemic in 150 countries, including India where it is present in all states and union territories except Andaman and Nicobar Islands Lakshadweep. Kerala reports high incidence of animal bites. This article discusses the preventable death of a 17-year-old tribal girl due to rabies in Kerala and the equity concerns it raises. METHODS: The case study was conducted using qualitative methods such as rapid key informant interviews, interactions in tribal assembly meetings, unstructured participant observations, and document verification. Thematic analysis was used, and the results are presented as an ethnographic summary with the use of quotes to substantiate the observations. RESULTS: The girl had gone to a town with her sister for a few days when she developed difficulty in eating, behavioral abnormalities, and injuries on her body. She subsequently died, and a post-mortem revealed Negri bodies in her brain, confirming rabies as the cause of death. The girl had been bitten by a puppy from the forest eight months prior, but she did not receive post-exposure prophylaxis. Multiple dogs are kept in each household in the settlement, and the community takes good care of them since they protect them from wild animals. However, awareness about the need for post-exposure prophylaxis is low, and access to it is difficult for this population. The social problems in the settlement affect their quality of life and their interactions with the outside world. CONCLUSIONS: To prevent such deaths, it is essential to increase awareness and ensure equitable access to life-saving vaccines and immunoglobulin in hard-to-reach tribal areas. The cost-effectiveness of pre-exposure prophylaxis for children in high-risk areas such as this tribal settlement should be evaluated and compared with the WHO-recommended strategies of mass canine vaccination and One Health.

Factors potentially contributing to the decline of the mpox outbreak in the Netherlands, 2022 and 2023.

BackgroundIn 2022 and 2023, a global outbreak of mpox affected mostly gay, bisexual and other men having sex with men (GBMSM). Outbreak control in the Netherlands included isolation, quarantine, post-exposure prophylaxis vaccination and primary preventive vaccination (PPV).AimWe describe the course of the outbreak, the vaccination programme, vaccine effectiveness (VE) of full vaccination against symptomatic disease, and trends in behaviour to generate hypotheses about factors that influenced the outbreak's decline.MethodsIn this observational study, we collected data from public health services on notified cases, number of PPV invitations and PPV doses administered. We calculated PPV uptake and coverage. Trends in behavioural data of GBMSM visiting sexual health centres were analysed for all consultations in 2022. We estimated VE using the screening method.ResultsUntil 31 December 2023, 1,294 mpox cases were reported. The outbreak peaked in early July 2022 and then declined sharply. PPV started on 25 July 2022; in total 29,851 doses were administered, 45.8% received at least one dose, 35.4% were fully vaccinated. The estimated VE was 68.2% (95% CI 4.3-89.5%). We did not observe an evident decrease in high-risk behaviour.DiscussionIt is unlikely that PPV was a driver of the outbreak's decline, as incidence started to decline well before the start of the PPV programme. The possible impact of behavioural change could not be demonstrated with the available indicators, however, the data had limitations, hampering interpretation. We hypothesise that infection-induced immunity in high-risk groups was an important factor explaining the decline.

The first confirmed human case of rabies, Timor-Leste, 2024.

In March 2024, the first ever human case of rabies, following a dog bite, was detected in Timor-Leste. This paper briefly discusses the circumstances of transmission, clinical presentation, palliative care of the case and public health measures taken. Timor-Leste was previously considered rabies-free. Any person who is bitten or scratched by an animal that could potentially transmit rabies virus (especially dogs, bats, monkeys or cats) in Timor-Leste should be assessed for consideration of provision of rabies post-exposure prophylaxis.

One-dose intradermal rabies booster enhances rabies antibody production and avidity maturation.

The incidence of rabies in Thailand reached its peak in 2018 with 18 human deaths. Preexposure prophylaxis (PrEP) vaccination is thus recommended for high-risk populations. WHO has recently recommended that patients who are exposed to a suspected rabid animal and have already been immunized against rabies should receive a 1-site intradermal (ID) injection of 0.1 mL on days 0 and 3 as postexposure prophylaxis (PEP). In Thailand, village health and livestock volunteers tasked with annual dog vaccination typically receive only a single lifetime PrEP dose and subsequent boosters solely upon confirmed animal bites. However, the adequacy of a single PrEP dose for priming and maintaining immunity in this high-risk group has not been evaluated. Therefore, our study was designed to address two key questions: (1) sufficiency of single-dose PrEP-to determine whether a single ID PrEP dose provides adequate long-term immune protection for high-risk individuals exposed to numerous dogs during their vaccination duties. (2) Booster efficacy for immune maturation-to investigate whether one or two additional ID booster doses effectively stimulate a mature and sustained antibody response in this population. The level and persistence of the rabies antibody were determined by comparing the immunogenicity and booster efficacy among the vaccination groups. Our study demonstrated that rabies antibodies persisted for more than 180 days after cost-effective ID PrEP or the 1st or the 2nd single ID booster dose, and adequate antibody levels were detected in more than 95% of participants by CEE-cELISA and 100% by indirect ELISA. Moreover, the avidity maturation of rabies-specific antibodies occurred after the 1st single ID booster dose. This smaller ID booster regimen was sufficient for producing a sufficient immune response and enhancing the maturation of anti-rabies antibodies. This safe and effective PrEP regimen and a single visit involving a one-dose ID booster are recommended, and at least one one-dose ID booster regimen could be equitably implemented in at-risk people in Thailand and other developing countries. However, an adequate antibody level should be monitored before the booster is administered.

Post-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trial.

BACKGROUND: Post-exposure prophylaxis (PEP) using single-dose rifampicin reduces progression from infection with Mycobacterium leprae to leprosy disease. We compared effectiveness of different administration modalities, using a higher (20 mg/kg) dose of rifampicin-single double-dose rifampicin (SDDR)-PEP. METHODS: We did a cluster randomised study in 16 villages in Madagascar and 48 villages in Comoros. Villages were randomly assigned to four study arms and inhabitants were screened once a year for leprosy, for 4 consecutive years. All permanent residents (no age restriction) were eligible to participate and all identified patients with leprosy were treated with multidrug therapy (SDDR-PEP was provided to asymptomatic contacts aged ≥2 years). Arm 1 was the comparator arm, in which no PEP was provided. In arm 2, SDDR-PEP was provided to household contacts of patients with leprosy, whereas arm 3 extended SDDR-PEP to anyone living within 100 m. In arm 4, SDDR-PEP was offered to household contacts and to anyone living within 100 m and testing positive to anti-phenolic glycolipid-I. The main outcome was the incidence rate ratio (IRR) of leprosy between the comparator arm and each of the intervention arms. We also assessed the individual protective effect of SDDR-PEP and explored spatial associations. This trial is registered with ClinicalTrials.gov, NCT03662022, and is completed. FINDINGS: Between Jan 11, 2019, and Jan 16, 2023, we enrolled 109 436 individuals, of whom 95 762 had evaluable follow-up data. Our primary analysis showed a non-significant reduction in leprosy incidence in arm 2 (IRR 0·95), arm 3 (IRR 0·80), and arm 4 (IRR 0·58). After controlling for baseline prevalence, the reduction in arm 3 became stronger and significant (IRR 0·56, p=0·0030). At an individual level SDDR-PEP was also protective with an IRR of 0·55 (p=0·0050). Risk of leprosy was two to four times higher for those living within 75 m of an index patient at baseline. INTERPRETATION: SDDR-PEP appears to protect against leprosy but less than anticipated. Strong spatial associations were observed within 75 m of index patients. Targeted door-to-door screening around index patients complemented by a blanket SDDR-PEP approach will probably have a substantial effect on transmission. FUNDING: European and Developing Countries Clinical Trials Partnership. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Comparative Effectiveness of Baloxavir Marboxil and Oseltamivir Treatment in Reducing Household Transmission of Influenza: A Post Hoc Analysis of the BLOCKSTONE Trial.

BACKGROUND: The transmission of influenza virus in households, especially by children, is a major route of infection. Prior studies suggest that timely antiviral treatment of ill cases may reduce infection in household contacts. The aim of the study was to compare the effects of oseltamivir (OTV) and baloxavir marboxil (BXM) treatment of index cases on the secondary attack rate (SAR) of influenza within household. METHODS: A post hoc analysis was done in BLOCKSTONE trial-a placebo-controlled, double-blinded post-exposure prophylaxis of BXM. Data were derived from the laboratory-confirmed index cases' household contacts who received placebo in the trial and also from household members who did not participate in the trial but completed illness questionnaires. To assess the SAR of household members, multivariate analyses adjusted for factors including age, vaccination status, and household size were performed and compared between contacts of index cases treated with BXM or OTV. RESULTS: In total, 185 index cases (116 treated with BXM and 69 treated with OTV) and 410 household contacts (201 from trial, 209 by questionnaire) were included. The Poisson regression modeling showed that the SAR in household contacts of index cases treated with BXM and OTV was 10.8% and 18.5%, respectively; the adjusted relative reduction in SAR was 41.8% (95% confidence interval: 1.0%-65.7%, p = 0.0456) greater with BXM than OTV. Similar reductions were found in contacts from the trial and those included by questionnaire. CONCLUSION: BXM treatment of index cases appeared to result in a greater reduction in secondary household transmission than OTV treatment.

The impact of socio-environmental factors on doxycycline post-exposure prophylaxis awareness in the US: a cross-sectional study.

Background We investigated awareness and use of doxycycline post-exposure prophylaxis (doxyPEP) in the US. DoxyPEP has preventative benefits for bacterial STIs among people assigned male at birth. We considered how individual, interpersonal and social determinants of health, such as state-level LGBTQ equality, impact doxyPEP awareness. Methods We conducted an online snapshot cross-sectional survey in June 2023. Survey questions included demographics, sexual and substance use behaviours, and socio-environmental factors, and provided a short explanation of doxyPEP, with questions regarding prior awareness and use. Results Among a racially diverse sample of 196 participants (median age 33 years), 94% identified as cisgender men, 26% were aware of doxyPEP, whereas only 14 (7%) had ever used it. Factors significantly associated with awareness included being college educated (OR 2.50, 95% CI 1.09-5.74), a past year bacterial STI (OR 4.20, 95% CI 1.97-8.89), having discussed HIV pre-exposure prophylaxis with a health care provider (OR 3.88, 95% CI 1.99-7.57) and having taken HIV pre-exposure prophylaxis (OR 2.29, 95% CI 1.11-4.70). Socio-environmental factors associated with doxyPEP awareness included living in a large urban city (OR 2.14, 95% CI 1.12-4.10) and living in a state with higher levels of LGBTQ policy equality (OR 2.18, 95% CI 1.07-4.44). Conclusions Considering the disproportionate impact of bacterial STIs on men who have sex with men, especially those living in lower LGBTQ equality regions, such as the Southern US, our study emphasises how socio-environmental factors may limit awareness and uptake of novel biomedical approaches that have the potential to prevent morbidity and enhance sexual health.

Characteristics and rates of infection by HIV in people receiving non-occupational post-exposure prophylaxis (nPEP) against HIV.

INTRODUCTION/OBJECTIVES: The use of non-occupational post-exposure prophylaxis (nPEP) emerges as a strategic intervention to reduce HIV infection risk following sexual encounters in our setting. Notwithstanding, there is a scarcity of contemporary data regarding adherence to this treatment, its effectiveness and tolerance. Our study aims to delve into these factors among individuals who have resorted to nPEP after high-risk sexual encounters. METHODS: We conducted a retrospective observational study of cases administered nPEP for HIV from 1 January 2018 to 31 December 2021 at a tertiary hospital in Madrid. The study included all adults over 18 years who sought care at the emergency department of the Fundación Jiménez Díaz Hospital following a risky sexual encounter and were subsequently recommended HIV nPEP treatment. RESULTS: 878 individuals received nPEP for HIV and underwent initial serological tests. Of these, 621 had comprehensive follow-ups. The prescribed regimen for all was raltegravir (RAL) 1200 mg combined with tenofovir/emtricitabine (TDF/FTC) 245/200 mg daily for 28 days. The study revealed a 1.1% rate (n=10) of previously undetected infection and a 0.16% (n=1) failure rate of nPEP. Regarding regimen tolerability, 5.6% (n=35) experienced symptoms linked to the treatment, yet none necessitated discontinuation of the regimen. On the contrary, six per cent (n=53) reported symptoms consistent with an STI during one of the medical visits; specifically, 4.4% had urethritis, and 1.6% had proctitis. CONCLUSION: nPEP with RAL/TDF/FTC demonstrates high efficacy and safety, contingent on proper adherence. There is an observed increase in STI prevalence in this cohort, with nearly half of the participants not engaging in appropriate follow-up after initiating nPEP.

45 years of tetracycline post exposure prophylaxis for STIs and the risk of tetracycline resistance: a systematic review and meta-analysis.

There is considerable interest in the use of doxycycline post exposure prophylaxis (PEP) to reduce the incidence of bacterial sexually transmitted infections (STIs). An important concern is that this could select for tetracycline resistance in these STIs and other species. We searched PubMed and Google Scholar, (1948-2023) for randomized controlled trials comparing tetracycline PEP with non-tetracycline controls. The primary outcome was antimicrobial resistance (AMR) to tetracyclines in all bacterial species with available data. Our search yielded 140 studies, of which three met the inclusion criteria. Tetracycline PEP was associated with an increasedprevalence of tetracycline resistance in Neisseria gonorrhoeae, but this effect was not statistically significant (Pooled OR 2.3, 95% CI 0.9-3.4). PEP had a marked effect on the N. gonorrhoeae tetracycline MIC distribution in the one study where this was assessed. Prophylactic efficacy was 100% at low MICs and 0% at high MICs. In the one study where this was assessed, PEP resulted in a significant increase in tetracycline resistance in commensal Neisseria species compared to the control group (OR 2.9, 95% CI 1.5-5.5) but no significant effect on the prevalence of tetracycline resistance in Staphylococcus aureus. The available evidence suggests that PEP with tetracyclines could be associated with selecting tetracycline resistance in N. gonorrhoeae and commensal Neisseria species.

Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China.

Objective: This study aimed to compare the current Essen rabies post-exposure immunization schedule (0-3-7-14-28) in China and the simple 4-dose schedule (0-3-7-14) newly recommended by the World Health Organization in terms of their safety, efficacy, and protection. Methods: Mice were vaccinated according to different immunization schedules, and blood was collected for detection of rabies virus neutralizing antibodies (RVNAs) on days 14, 21, 28, 35, and 120 after the first immunization. Additionally, different groups of mice were injected with lethal doses of the CVS-11 virus on day 0, subjected to different rabies immunization schedules, and assessed for morbidity and death status. In a clinical trial, 185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule, and blood was collected for RVNAs detection on days 28 and 42 after the first immunization. Results: A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day ( P < 0.05). The groups 0-3-7-14, 0-3-7-21, and 0-3-7-28 showed no statistically significant difference ( P > 0.05) in RVNAs levels at any time point. The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%, whereas that in the immunization groups was 40%. In the clinical trial, the RVNAs positive conversion rates on days 28 (14 days after 4 doses) and 42 (14 days after 5 doses) were both 100%, and no significant difference in RVNAs levels was observed ( P > 0.05). Conclusion: The simple 4-dose schedule can produce sufficient RVNAs levels, with no significant effect of a delayed fourth vaccine dose (14-28 d) on the immunization potential.

[Perception of risk of HIV infection and knowledge about the use of antiretrovirals in prevention]. / Percepción de riesgo de infección por HIV y conocimiento sobre uso de antirretrovirales en prevención.

INTRODUCTION: Combined prevention (CP) is considered the key strategy against the HIV epidemic. The objective of the study was to evaluate the perception of risk of HIV infection and the knowledge about the use of antiretrovirals (ARV) for prevention, among patients who attend a Sexually Transmitted Infections (STI) clinic. METHODS: A survey on personal data and perception of risk of HIV infection, knowledge about post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP), was administered to patients at the time of applying doses of penicillin for the treatment of syphilis, or when taking a blood sample for STI diagnosis, between May and December, 2022. RESULTS: 100 persons were surveyed: 43 were under 25 years of age, 67 reported male sex-gender and 33 females. Thirty of 91 (33%) perceived they had had some risk of infection in their lives, 19 of them in the last year; 77/96 (80%) stated that they had no knowledge about PEP, and 82/100, about PrEP. Only 22 out of 100 responded that antiretrovirals could provide benefit in preventing HIV; 26 (60%) of the 43 patients <25 years of age, and 18 of the 57 ≥ 25 years (31.6%) responded they have had two or more sexual partners in the last year. No statistically significant differences were observed related to gender and age group. DISCUSSION: The low perception of infection risk and knowledge about the use of antiretrovirals in HIV prevention, show the existing difficulties for the implementation of combined prevention (PEP-PrEP) in this population.

Introducción: La prevención combinada (PC) se considera la estrategia clave frente a la epidemia de HIV. El objetivo del estudio fue evaluar la percepción de riesgo de infección por HIV y el conocimiento sobre uso de antirretrovirales (ARV) para prevención, entre pacientes que concurren a un consultorio de Infecciones de Transmisión Sexual (ITS). Métodos: Una encuesta sobre datos personales y percepción de riesgo de infección por HIV, conocimiento sobre profilaxis posterior a la exposición (PEP) y previa a la exposición (PrEP), fue administrada a pacientes al momento de aplicar dosis de penicilina para tratamiento de sífilis, o de extraer muestra de sangre para diagnóstico de ITS, entre mayo y diciembre, 2022. Resultados: De 100 personas encuestadas, 43 eran menores de 25 años, 67 reportaron sexo-género masculino y 33 femenino. Treinta de 91, (33%), percibían haber tenido en su vida algún riesgo de infección, 19 de ellas en el último año; 77/96 (80%) manifestaron no tener conocimiento sobre PEP, y 82/100, sobre PrEP. Solo 22% respondió que los antirretrovirales podrían brindar beneficio para prevenir el HIV; 26 (60%) de los 43 menores de 25 años, y 18 de los 57 ≥ 25 años (31.6%) respondieron haber tenido dos o más parejas sexuales el último año. No se observaron diferencias estadísticamente significativas, relacionadas con género y grupo etario. Discusión: La baja percepción de riesgo de infección y del conocimiento sobre uso de antirretrovirales para prevención de HIV, evidencian las dificultades existentes en la implementación de prevención combinada (PEPPrEP) en esta población.

A behavioral economics approach to enhancing HIV preexposure and postexposure prophylaxis implementation.

PURPOSE OF REVIEW: The 'PrEP cliff' phenomenon poses a critical challenge in global HIV PrEP implementation, marked by significant dropouts across the entire PrEP care continuum. This article reviews new strategies to address 'PrEP cliff'. RECENT FINDINGS: Canadian clinicians have developed a service delivery model that offers presumptive PEP to patients in need and transits eligible PEP users to PrEP. Early findings are promising. This service model not only establishes a safety net for those who were not protected by PrEP, but it also leverages the immediate salience and perceived benefits of PEP as a natural nudge towards PrEP use. Aligning with Behavioral Economics, specifically the Salience Theory, this strategy holds potential in tackling PrEP implementation challenges. SUMMARY: A natural pathway between PEP and PrEP has been widely observed. The Canadian service model exemplifies an innovative strategy that leverages this organic pathway and enhances the utility of both PEP and PrEP services. We offer theoretical insights into the reasons behind these PEP-PrEP transitions and evolve the Canadian model into a cohesive framework for implementation.

[Bad luck or a common reality? Multiple exposures a nurse to potentially infectious material: a case report]. / Pech czy powszechna rzeczywistosc? Liczne ekspozycje pielegniarki na material potencjalnie zakazny: opis przypadku.

Presented is the case of a nurse who had 4 occupational exposures to potentially infectious material between December 2020 and June 2022. In 2 of the cases, the source patient was unknown, so pharmacological HIV post-exposure prophylaxis was implemented (in 1 of these cases, the nurse developed weakness and increased dyspeptic symptoms, necessitating a change in the antiretroviral medications used). During the interview collection, the nurse reported that multiple exposures to potentially infectious material are common in her work environment, but most of these are not reported. This is supported by the results of several studies devoted to the problem of non-reporting of occupational exposures by health care workers. However, there is significant discrepancy in the results of these studies, which may be due to different methods. The authors of this article believe that after 10 years since the entry into force of the regulation of the Minister of Health standardizing procedures for dealing with injuries caused by sharp instruments used in the provision of health care services, a serious problem remains of non-reporting of cases by employees (resulting in a lack of post-exposure prophylaxis). The authors call for the introduction of a nationwide reporting system. There is also a need to increase the importance of prophylaxis of stabbings and to improve the quality of training of medical personnel in post-exposure prophylaxis procedures. Med Pr Work Health Saf. 2024;75(2):173-179.

Utilization of post-exposure prophylaxis potentially contributed to the changes of risk behaviors among men who have sex with men in China.

Background: The HIV infection status among men who have sex with men (MSM) in China is a cause for concern. Post-exposure prophylaxis (PEP) serves as a highly effective biomedical preventive measure against HIV infection. Substantial evidence has established an association between PEP utilization and risk behaviors among MSM, but whether the utilization of PEP has an impact on risk behaviors remains unknown. This study sought to elucidate the impact of PEP usage on risk behaviors among MSM and provide recommendations for developing targeted HIV prevention programs. Methods: A cohort study was conducted in Qingdao, China, from April 2021 to January 2022. Participants were enlisted by volunteers from community-based organizations through a snowball sampling method. Face-to-face interviews were conducted to collect sociodemographic and behavioral information of participants. The study encompassed a retrospective investigation, baseline survey, and follow-up survey, representing periods before, during, and after PEP usage, respectively. Generalized estimating equations, fitting a Poisson regression model, were applied to scrutinize changes in risk behaviors of MSM during and after PEP usage, in comparison to before PEP usage. Results: A total of 341 MSM were recruited in the cohort study, with 179 individuals completing the follow-up survey. In comparison to before PEP usage, there was a significant increase in the proportion of Rush Popper usage (17.6% vs. 23.8% vs. 29.6%) and commercial sexual partners (10.9% vs. 17.6% vs. 21.8%) among MSM during and after PEP usage. Before PEP usage, 88.7% of MSM reported having ≥3 temporary sexual partners in the last 6 months. This proportion exhibited no significant change during PEP usage (91.8%), but it significantly increased to 97.8% after PEP usage (P < 0.05). Notably, there was a significant decrease in group sex during and after PEP usage compared to before PEP usage (30.8% vs. 21.4% vs. 21.2%). Conclusion: The utilization of PEP may impact risk behaviors among MSM, potentially leading to increased Rush Popper usage, temporary sexual partners, and commercial sexual partners after PEP usage, accompanied by a decrease in group sex. Further research is imperative to elucidate the impact of PEP utilization on MSM and develop targeted HIV prevention programs.

Doxycycline as Postsexual Exposure Prophylaxis: Use, Acceptability, and Associated Sexual Health Behaviors Among a Multi-Site Sample of Clinical Trial Participants.

Doxycycline postexposure prophylaxis (doxy-PEP) reduces sexually transmitted infections (STIs) in men who have sex with men (MSM) and transgender women (TGW). In a clinical trial of doxy-PEP, we sought to assess acceptability, impact, and meaning of doxy-PEP use among MSM/TGW. We conducted semistructured, in-depth 1:1 interviews with MSM and TGW enrolled in the intervention arm of the Doxy-PEP study. We queried motivations for and meaning of use, attitudes, beliefs, adherence, effect on sexual behaviors, and partner, community, and structural factors related to use. We coded interview transcripts into content areas, followed by thematic analysis. We interviewed 44 participants (median age 38), 2% were TGW, 17% Black, 61% White, 30% Hispanic, and 45% persons with HIV. We identified three overarching themes. First, participants found doxy-PEP acceptable, and believed it was effective based on their history of STIs, easy to adhere to, and acceptable to sex partners. Second, doxy-PEP benefited their quality of life and mental health, offering "peace of mind" by reducing their anxiety about acquisition or unwitting transmission of STIs. Participants reported feeling more "in control" of preventing STIs, and positive about supporting their personal, partner, and community health. Third, impact on sexual behavior was variable, with most reporting no change or a brief initial change. Participants in a multi-site clinical trial of doxycycline for STI prevention perceived it to be efficacious, and that it provided quality-of-life benefits, including reduced anxiety and sense of control over sexual health. Doxy-PEP had limited impact on sexual behavior. Clinicaltrials.gov: NCT03980223.

Mitoquinone mesylate as post-exposure prophylaxis against SARS-CoV-2 infection in humans: an exploratory single center pragmatic open label non-randomized pilot clinical trial with matched controls.

BACKGROUND: An ongoing important need exists to rapidly develop novel therapeutics for COVID-19 that will retain antiviral efficacy in the setting of rapidly evolving SARS-CoV-2 variants and potential future development of resistance of SARS-COV-2 to remdesivir and protease inhibitors. To date, there is no FDA-approved treatment for post-exposure prophylaxis against SAR-CoV-2. We have shown that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has antiviral activity against SARS-CoV-2 in vitro and in SARS-CoV-2 infected K18-hACE2 mice. METHODS: In this exploratory, pragmatic open label clinical trial (ClinicalTrials.gov identifier NCT05381454), we studied whether Mito-MES is an effective post-exposure prophylaxis treatment in people who had high-grade unmasked exposures to SARS-CoV-2 within 5 days prior to study entry. Participants were enrolled in real-world setting in Los Angeles, United States between May 1 and December 1, 2022 and were assigned to either mito-MES 20 mg daily for 14 days (n = 40) or no mito-MES (controls) (n = 40). The primary endpoint was development of SARS-CoV-2 infection based on 4 COVID-19 diagnostic tests [rapid antigen tests (RATs) or PCR] performed during the study period (14 days post exposure). FINDINGS: Out of 40 (23 females; 57.5%) study participants who took Mito-MES, 12 (30%) developed SARS-CoV-2 infection compared to 30 of the 40 controls (75%) (difference -45.0%, 95% confidence intervals (CI): -64.5%, -25.5%). Out of 40 (19 females; 47.5%) study participants in the control group, 30 (75.0%) had at least one positive COVID-19 diagnostic test and 23 (57.5%) were symptomatic. With regards to key secondary outcomes, among symptomatic SARS-CoV-2 infections, the median duration of viral symptoms was lower in the Mito-MES group (median 3.0, 95% CI 2.75, 3.25) compared to the control group (median 5.0, 95% CI 4.0, 7.0). None of the study participants was hospitalized or required oxygen therapy. Mito-MES was well tolerated and no serious side effect was reported in any study participant. INTERPRETATION: This work describes antiviral activity of mito-MES in humans. Mito-MES was well tolerated in our study population and attenuated transmission of SARS-CoV-2 infection. Given established safety of Mito-MES in humans, our results suggest that randomized control clinical trials of Mito-MES as post-exposure prophylaxis against SARS-CoV-2 infection are warranted. FUNDING: This work was supported in part by National Institutes of Health grant R01AG059501 (TK), National Institutes of Health grant R01AG059502 04S1 (TK), NIH/National Center for Advancing Translational Sciences (NCATS) UCLA CTSI Grant Number UL1TR001881 and California HIV/AIDS Research Program grant OS17-LA-002 (TK).