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Doxycycline post-exposure prophylaxis (doxy-PEP) is a promising intervention to reduce bacterial sexually transmitted infections (STIs). We evaluated the effect of doxy-PEP on STI incidence and antimicrobial resistance in men who have sex with men and transgender women for up to 12 months of follow-up, inlcuding an open-label extension. DoxyPEP, an open-label trial in Seattle (WA, USA) and San Francisco (CA, USA) among men who have sex with men and transgender women with at least one bacterial STI in the past year, randomly assigned participants by clinic (with computer-generated variable block sizes) 2:1 to doxy-PEP (200 mg doxycycline delayed-release tablets 24–72 h after condomless sex) or standard care. The independent endpoint adjudication committee was masked to group assignment. The primary outcome was presence of one or more bacterial STIs (Neisseria gonorrhoeae, Chlamydia trachomatis, or early syphilis) each quarter. This outcome was assessed in the modified intention-to-treat cohort, which included participants with at least one follow-up quarter (ie, ∼3 months) in their as-randomised assignment. After early termination of the randomised phase for efficacy, all participants still enrolled were offered doxy-PEP in an open-label extension (OLE). We report quarterly incidence of bacterial STIs for the as-randomised and OLE periods. Safety was assessed in all participants with any follow-up data. The trial was registered with ClinicalTrials.gov (NCT03980223) and is completed. From Aug 19, 2020, to May 13, 2022, we enrolled 637 participants; 592 participants completed at least one follow-up quarter in the randomised phase (411 in the doxy-PEP group and 181 in the standard-care group) and 282 in the OLE phase (207 in the doxy-PEP group and 82 in the standard-care group). STIs were present in 129 (12·0%) of 1077 quarters in the doxy-PEP group versus 139 (30·5%) of 455 quarters in the standard-care group during the as-randomised period, showing an absolute difference of 19 percentage points and a relative risk of 0·39 (95% CI 0·31–0·49, p<0·0001). During the OLE, STIs were diagnosed in 51 (13%) of 388 quarters among those continuing doxy-PEP and 25 (17%) of 145 quarters among standard-care participants who initiated doxy-PEP. Throughout all quarters for participants on doxy-PEP, there was one grade 2 laboratory abnormality and five grade 3 adverse events that were possibly or probably related to doxy-PEP. No serious adverse events were attributed by site investigators to doxycycline. Of participants with positive gonorrhoea cultures during the study, eight (27%) of 29 taking doxy-PEP versus five (24%) of 21 not taking doxy-PEP had tetracycline resistance (minimum inhibitory concentration ≥2 μg/mL). Doxy-PEP was effective in reducing bacterial STIs in this population of men who have sex with men and transgender women, including during an open-label extension when doxy-PEP efficacy was known. Doxy-PEP was well tolerated, highly acceptable, and with no new safety signals. US National Institutes of Health.

Increased rates of sexually transmitted infections (STIs) are reported among men who have sex with men (MSM) and new interventions are needed. We aimed to assess whether post-exposure prophylaxis (PEP) with doxycycline could reduce the incidence of chlamydia or syphilis (or both) and whether the meningococcal group B vaccine (4CMenB) could reduce the incidence of gonorrhoea in this population. ANRS 174 DOXYVAC is a multicentre, open-label, randomised trial with a 2 × 2 factorial design conducted at ten hospital sites in Paris, France. Eligible participants were MSM aged 18 years or older, HIV negative, had a history of bacterial STIs within the 12 months before enrolment, and who were already included in the ANRS PREVENIR study (a cohort of MSM using pre-exposure prophylaxis with tenofovir and emtricitabine for HIV prevention). Participants were randomly assigned (2:1) to doxycycline PEP (two pills of 100 mg each orally within 72 h after condomless sex, with no more than three doses of 200 mg per week) or no PEP groups and were also randomly assigned (1:1) to the 4CMenB vaccine (GlaxoSmithKline, Paris, France; two intramuscular injections at enrolment and at 2 months) or no vaccine groups, using a computer-generated randomisation list with a permuted fixed block size of four. Follow-up occurred for at least 12 months (with visits every 3 months) up to 24 months. The coprimary outcomes were the risk of a first episode of chlamydia or syphilis (or both) after the enrolment visit at baseline for the doxycycline intervention and the risk of a first episode of gonorrhoea starting at month 3 (ie, 1 month after the second vaccine dose) for the vaccine intervention, analysed in the modified intention-to-treat population (defined as all randomly assigned participants who had at least one follow-up visit). This trial is registered with ClinicalTrials.gov, NCT04597424 (ongoing). Between Jan 19, 2021, and Sept 19, 2022, 556 participants were randomly assigned. 545 (98%) participants were included in the modified intention-to-treat analysis for the doxycycline PEP and no PEP groups and 544 (98%) were included for the 4CMenB vaccine and no vaccine groups. The median follow-up was 14 months (IQR 9–18). The median age was 40 years (34–48) and all 545 participants were male. There was no interaction between the two interventions (p≥0·1) for the primary outcome. The incidence of a first episode of chlamydia or syphilis (or both) was 8·8 per 100 person-years (35 events in 362 participants) in the doxycycline PEP group and 53·2 per 100 person-years (80 events in 183 participants) in the no PEP group (adjusted hazard ratio [aHR] 0·17 [95% CI 0·12–0·26]; p<0·0001). The incidence of a first episode of gonorrhoea, starting from month 3 was 58·3 per 100 person-years (103 events in 274 participants) in the 4CmenB vaccine group and 77·1 per 100 person-years (122 events in 270 participants) in the no vaccine group (aHR 0·78 [95% CI 0·60–1·01]; p=0·061). There were no deaths during the study. One drug-related serious adverse event (fixed-drug eruption) occurred in the doxycycline PEP group. Six (2%) participants in the doxycycline group discontinued doxycycline PEP because of gastrointestinal adverse events. Doxycycline PEP strongly reduced the incidence of chlamydia and syphilis in MSM, but we did not show efficacy of the 4CmenB vaccine for gonorrhoea. Doxycycline PEP should be assessed in other populations, such as heterosexual men and women, and its effect on antimicrobial resistance carefully monitored. ANRS Maladies Infectieuses Emergentes. For the French translation of the abstract see Supplementary Materials section.

In an open-label, randomized study involving men who have sex with men, doxycycline use after high-risk sexual exposure reduced the incidence of sexually transmitted infections (chlamydia, gonorrhea, and syphilis).

WHO estimated that nearly 1 million people become infected every day with any of four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea, syphilis, and trichomoniasis. Despite their high global incidence, STIs remain a neglected area of research. In this Commission, we have prioritised five areas that represent particular challenges in STI treatment and control. Chlamydia remains the most commonly diagnosed bacterial STI in high-income countries despite widespread testing recommendations, sensitive and specific non-invasive testing techniques, and cheap effective therapy. We discuss the challenges for chlamydia control and evidence to support a shift from the current focus on infection-based screening to improved management of diagnosed cases and of chlamydial morbidity, such as pelvic inflammatory disease. The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is globally recognised. We review current and potential future control and treatment strategies, with a focus on novel antimicrobials. Bacterial vaginosis is the most common vaginal disorder in women, but current treatments are associated with frequent recurrence. Recurrence after treatment might relate to evidence that suggests sexual transmission is integral to the pathogenesis of bacterial vaginosis, which has substantial implications for the development of effective management approaches. STIs disproportionately affect low-income and middle-income countries. We review strategies for case management, focusing on point-of-care tests that hold considerable potential for improving STI control. Lastly, STIs in men who have sex with men have increased since the late 1990s. We discuss the contribution of new biomedical HIV prevention strategies and risk compensation. Overall, this Commission aims to enhance the understanding of some of the key challenges facing the field of STIs, and outlines new approaches to improve the clinical management of STIs and public health.

Expedited partner therapy (EPT), the practice of treating the sex partners of persons with sexually transmitted infections without their medical evaluation, increases partner treatment and decreases gonorrhea and chlamydia reinfection rates. We conducted a stepped-wedge, community-level randomized trial to determine whether a public health intervention promoting EPT could increase its use and decrease chlamydia test positivity and gonorrhea incidence in women. The trial randomly assigned local health jurisdictions (LHJs) in Washington State, US, into four study waves. Waves instituted the intervention in randomly assigned order at intervals of 6-8 mo. Of the state's 25 LHJs, 24 were eligible and 23 participated. Heterosexual individuals with gonorrhea or chlamydial infection were eligible for the intervention. The study made free patient-delivered partner therapy (PDPT) available to clinicians, and provided public health partner services based on clinician referral. The main study outcomes were chlamydia test positivity among women ages 14-25 y in 219 sentinel clinics, and incidence of reported gonorrhea in women, both measured at the community level. Receipt of PDPT from clinicians was evaluated among randomly selected patients. 23 and 22 LHJs provided data on gonorrhea and chlamydia outcomes, respectively. The intervention increased the percentage of persons receiving PDPT from clinicians (from 18% to 34%, p < 0.001) and the percentage receiving partner services (from 25% to 45%, p < 0.001). Chlamydia test positivity and gonorrhea incidence in women decreased over the study period, from 8.2% to 6.5% and from 59.6 to 26.4 per 100,000, respectively. After adjusting for temporal trends, the intervention was associated with an approximately 10% reduction in both chlamydia positivity and gonorrhea incidence, though the confidence bounds on these outcomes both crossed one (chlamydia positivity prevalence ratio = 0.89, 95% CI 0.77-1.04, p = 0.15; gonorrhea incidence rate ratio = 0.91, 95% CI .71-1.16, p = 0.45). Study findings were potentially limited by inadequate statistical power, by the institution of some aspects of the study intervention outside of the research randomization sequence, and by the fact that LHJs did not constitute truly isolated sexual networks. A public health intervention promoting the use of free PDPT substantially increased its use and may have resulted in decreased chlamydial and gonococcal infections at the population level. ClinicalTrials.gov NCT01665690.

WHO recommends that men who have sex with men (MSM) receive gonorrhoea and chlamydia testing, but many evidence-based preventive services are unaffordable. The pay-it-forward strategy offers an individual a gift (eg, a test for sexually transmitted diseases) and then asks whether they would like to give a gift (eg, a future test) to another person. This study examined the effectiveness of a pay-it-forward programme to increase gonorrhoea and chlamydia testing among MSM in China. We did a randomised controlled superiority trial at three HIV testing sites run by MSM community-based organisations in Guangzhou and Beijing, China. We included MSM aged 16 years or older who were seeking HIV testing and met indications for gonorrhoea and chlamydia testing. Restricted randomisation was done using computer-generated permuted blocks. 30 groups were randomised into three arms (1:1:1): a pay-it-forward arm in which men were offered free gonorrhoea and chlamydia testing and then asked whether they would like to donate for testing of prospective participants, a pay-what-you-want arm in which men were offered free testing and given the option to pay any desired amount for the test, and a standard-of-care arm in which testing was offered at ¥150 (US$22). There was no masking to arm assignment. The primary outcome was gonorrhoea and chlamydia test uptake ascertained by administrative records. We used generalised estimating equations to estimate intervention effects with one-sided 95% CIs and a prespecified superiority margin of 20%. The trial is registered with ClinicalTrials.gov, NCT03741725. Between Dec 8, 2018, and Jan 19, 2019, 301 men were recruited and included in the analysis. 101 were randomly assigned to the pay-it-forward group, 100 to the pay-what-you-want group, and 100 to the standard-of-care group. Test uptake for gonorrhoea and chlamydia was 56% (57 of 101 participants) in the pay-it-forward arm, 46% (46 of 100 participants) in the pay-what-you-want arm, and 18% (18 of 100 participants) in the standard-of-care arm. The estimated difference in test uptake between the pay-it-forward and standard-of-care group was 38·4% (95% CI lower bound 28·4%). Among men in the pay-it-forward arm, 54 of 57 (95%) chose to donate to support testing for others. The pay-it-forward strategy can increase gonorrhoea and chlamydia testing uptake among Chinese MSM and could be a useful tool for scaling up preventive services that carry a mandatory fee. US National Institute of Health; Special Programme for Research and Training in Tropical Diseases, sponsored by UNICEF, UNDP, World Bank, and WHO; the National Key Research and Development Program of China; Doris Duke Charitable Foundation; and Social Entrepreneurship to Spur Health.