Comparison of trends in rates of sexually transmitted infections before vs after initiation of HIV preexposure prophylaxis among men who have sex with men

Importance: There have been concerns that HIV preexposure prophylaxis (PrEP) may be associated with increases in sexually transmitted infections (STIs) because of subsequent reductions in condom use and/or increases in sexual partners. Objective: To determine trends in STI test positivity among high-risk men who have sex with men (MSM) before and after the start of HIV PrEP. Design, setting, and participants: A before-after analysis was conducted using a subcohort of a single-group PrEP implementation study cohort in New South Wales, Australia (Expanded PreEP Implementation in Communities in New South Wales [EPIC-NSW]), from up to 1 year before enrollment if after January 1, 2015, and up to 2 years after enrollment and before December 31, 2018. STI testing data were extracted from a network of 54 sexual health clinics and 6 primary health care clinics Australia-wide, using software to deidentify, encrypt, and anonymously link participants between clinics. A cohort of MSM dispensed PrEP for the first time during the study, with 2 or more STI tests in the prior year and who tested during follow-up, were included from the EPIC-NSW cohort of HIV-negative participants with high-risk sexual behavior. Data analysis was performed from June to December 2019. Exposures: Participants were dispensed coformulated tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) as HIV PrEP. Main outcomes and measures: The main outcome was STI, measured using test positivity, defined as the proportion of participants testing positive for an STI at least once per quarter of follow-up. Outcomes were calculated for Chlamydia trachomatis and Neisseria gonorrhoea by site of infection (anorectal, pharyngeal, urethral, or any) and for syphilis. Results: Of the EPIC-NSW cohort of 9709 MSM, 2404 were included in the before-after analysis. The mean (SD) age of the participants was 36 (10.4) years, and 1192 (50%) were Australia-born. STI positivity was 52% in the year after PrEP (23.3% per quarter; 95% CI, 22.5%-24.2% per quarter) with no significant trend (mean rate ratio [RR] increase of 1.01 per quarter [95% CI, 0.99-1.02]; P = .29), compared with 50% positivity in the year prior to PrEP (20.0% per quarter [95% CI, 19.04%-20.95% per quarter]; RR for overall STI positivity, 1.17 [95% CI, 1.10-1.24]; P < .001), with an increase in quarterly STI positivity (mean RR of 1.08 per quarter, or an 8% increase per quarter [95% CI, 1.05-1.11]; P < .001; RR, 0.93 [95% CI, 0.90-0.96]; P < .001). Findings were similar when stratified by specific STIs and anatomical site. Conclusions and relevance: STI rates were high but stable among high-risk MSM while taking PrEP, compared with a high but increasing trend in STI positivity before commencing PrEP. These findings suggest the importance of considering trends in STIs when describing how PrEP use may be associated with STI incidence

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88–1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. US National Institutes of Health and Operation Warp Spee