Pre-exposure prophylaxis with hydroxychloroquine for COVID-19: a double-blind, placebo-controlled randomized clinical trial.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a promising strategy to break COVID-19 transmission. Although hydroxychloroquine was evaluated for treatment and post-exposure prophylaxis, it is not evaluated for COVID-19 PrEP yet. The aim of this study was to evaluate the efficacy and safety of PrEP with hydroxychloroquine against placebo in healthcare workers at high risk of SARS-CoV-2 infection during an epidemic period. METHODS: We conducted a double-blind placebo-controlled randomized clinical trial in three hospitals in Barcelona, Spain. From 350 adult healthcare workers screened, we included 269 participants with no active or past SARS-CoV-2 infection (determined by a negative nasopharyngeal SARS-CoV-2 PCR and a negative serology against SARS-CoV-2). Participants allocated in the intervention arm (PrEP) received 400 mg of hydroxychloroquine daily for the first four consecutive days and subsequently, 400 mg weekly during the study period. Participants in the control group followed the same treatment schedule with placebo tablets. RESULTS: 52.8% (142/269) of participants were in the hydroxychloroquine arm and 47.2% (127/269) in the placebo arm. Given the national epidemic incidence decay, only one participant in each group was diagnosed with COVID-19. The trial was stopped due to futility and our study design was deemed underpowered to evaluate any benefit regarding PrEP efficacy. Both groups showed a similar proportion of participants experiencing at least one adverse event (AE) (p=0.548). No serious AEs were reported. Almost all AEs (96.4%, 106/110) were mild. Only mild gastrointestinal symptoms were significantly higher in the hydroxychloroquine arm compared to the placebo arm (27.4% (39/142) vs 15.7% (20/127), p=0.041). CONCLUSIONS: Although the efficacy of PrEP with hydroxychloroquine for preventing COVID-19 could not be evaluated, our study showed that PrEP with hydroxychloroquine at low doses is safe. TRIAL REGISTRATION: ClinicalTrials.gov NCT04331834 . Registered on April 2, 2020.

Indicator condition-guided HIV testing with an electronic prompt in primary healthcare: a before and after evaluation of an intervention.

OBJECTIVE: Indicator condition (IC)-guided HIV testing is a strategy for the diagnosis of patients with HIV. The aim of this study was to assess the impact on the proportion of HIV tests requested after the introduction of an electronic prompt instructing primary healthcare (PHC) physicians to request an HIV test when diagnosing predefined IC. METHODS: A prospective interventional study was conducted in 2015 in three PHC centres in Barcelona to assess the number of HIV test requests made during the implementation of an electronic prompt. Patients aged 18-65 years without HIV infection and with a new diagnosis of predefined IC were included. The results were compared with preprompt (2013) and postprompt data (2016). RESULTS: During the prompt period, 832 patients presented an IC (median age 41.6 years [IQR 30-54], 48.2% female). HIV tests were requested in 296 individuals (35, 6%) and blood tests made in 238. Four HIV infections were diagnosed (positivity rate 1.7%, 95% CI 0.5% to 4.4%). The number of HIV tests requested based on IC increased from 12.6% in 2013 to 35.6% in 2015 (p<0.001) and fell to 17.9% after removal of the prompt in 2016 (p<0.001). Younger patient age (OR 0.97, 95% CI 0.96 to 0.98), birth outside Spain (OR 1.53, 95% CI 1.06 to 2.21) and younger physician age (OR 0.97, 95% CI 0.96 to 0.99) were independent predictive factors for an HIV test request during the prompt period. The electronic prompt (OR 3.36, 95% CI 2.70 to 4.18) was the factor most closely associated with HIV test requests. It was estimated that 10 (95% CI 3.0 to 26.2) additional new cases would have been diagnosed if an HIV test had been performed in all patients presenting an IC. CONCLUSIONS: A significant increase in HIV test requests was observed during the implementation of the electronic prompt. The results suggest that this strategy could be useful in increasing IC-guided HIV testing in PHC centres.