Background Tenofovir and emtricitabine interfere with the SARS CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). Several cohorts reported that people treated by tenofovir disoproxil fumarate and emtricitabine are less likely to develop SARS CoV-2 infection and related severe COVID-19. Methods We conducted a pilot randomized, open-label, controlled, phase 2 trial at two hospitals in France. Eligible patients were consecutive outpatients (aged ≥18 years) with RT-PCR-confirmed SARS-CoV-2 infection and an interval from symptom onset to enrolment of 7 days or less. Patients were randomly assigned in a 1:1 ratio to receive oral tenofovir disoproxil fumarate and emtricitabine (2 pills on day 1 followed by 1 pill per day on days 2–7) or the standard of care. The primary and secondary endpoints were SARS-CoV-2 viral clearance from baseline assessed by cycle threshold (Ct) RT-PCR on nasopharyngeal swab collected at day 4 and day 7, respectively. A higher Ct corresponds to a lower SARS CoV-2 viral burden. Other endpoints were the time to recovery and the number of adverse events. This trial is registered with ClinicalTrials.gov, NCT04685512. Findings From November, 20 th 2020 to March, 19 th 2021, 60 patients were enrolled and randomly assigned to a treatment group (30 to tenofovir disoproxil fumarate and emtricitabine and 30 to standard of care). The median number of days from symptom onset to inclusion was 4 days (IQR 3–5) in both groups. Amongst patients who received tenofovir disoproxil fumarate, the difference from standard of care in the increase in Ct RT-PCR from baseline was 2.3 (95% confidence interval [-0.6 to 5.2], p = 0.13) at day 4 and 2.9 (95% CI [0.1 to 5.2], p = 0.044) at day 7. At day 7, 6/30 in the tenofovir disoproxil fumarate and emtricitabine group and 3/30 in the standard of care group reported no COVID-related symptoms. Adverse events included 11 cases of gastrointestinal side effects (grade ≤ 2), three of which leaded to drug discontinuation. Three patients had COVID-19 related hospitalisation, no participant died. Interpretation In this pilot study of outpatients adult with recent non-severe COVID-19, tenofovir disoproxil fumarate plus emtricitabine appeared to accelerate the natural clearance of nasopharyngeal SARS-CoV-2 viral burden. These findings support the conduct of larger trials of tenofovir-based therapies for the prevention and early treatment of COVID-19. Funding No external funding.
【초록키워드】 COVID-19, SARS CoV-2, therapy, Trial, Open-label, severe COVID-19, SARS-COV-2 infection, hospital, Infection, RT-PCR, adverse events, Randomized, Nasopharyngeal swab, Cohort, cycle threshold, nasopharyngeal, early treatment, Patient, France, RdRP, Time to recovery, RNA polymerase, hospitalisation, Other, funding, phase 2 trial, Outpatient, fumarate, tenofovir, Support, Standard of care, symptom onset, Adverse, Endpoint, 95% CI, 95% confidence interval, secondary endpoint, pilot study, Registered, treatment group, enrolment, viral burden, finding, clearance, Inclusion, event, Randomly, drug discontinuation, SARS-CoV-2 viral, enrolled, collected, develop, died, reported, conducted, median, treated, per day, less, increase in, interfere, assigned, accelerate, receive, 1:1, baseline, COVID-related symptoms, gastrointestinal side effect, in both groups, IQR, 【제목키워드】 Open-label, Randomized, nasopharyngeal, phase 2 trial, Outpatient, tenofovir, emtricitabine, SARS-CoV-2 viral load, Effect,