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Effect of Tenofovir Disoproxil Fumarate and Emtricitabine on nasopharyngeal SARS-CoV-2 viral load burden amongst outpatients with COVID-19: A pilot, randomized, open-label phase 2 trial

Parienti et al., eClinicalMedicine, doi:10.1016/j.eclinm.2021.100993, AR0-CORONA, NCT04685512, Aug 2021
https://c19early.org/parienti.html
Hospitalization -100% Improvement Relative Risk Recovery 11% Viral clearance, day 4 37% Viral clearance, day 7 25% Tenofovir  AR0-CORONA  EARLY TREATMENT  DB RCT Is early treatment with Tenofovir + emtricitabine beneficial for COVID-19? Double-blind RCT 60 patients in France (November 2020 - March 2021) Improved recovery (p=0.47) and viral clearance (p=0.1), not sig. c19early.org Parienti et al., eClinicalMedicine, Aug 2021 FavorsTenofovir Favorscontrol 0 0.5 1 1.5 2+
RCT 60 outpatients with mild/moderate COVID-19 showing no significant clinical benefit with tenofovir disoproxil fumarate plus emtricitabine. The primary endpoint of viral load reduction at day 4 was not met (p=0.13), though a secondary endpoint showed viral load reduction at day 7 (p=0.044). There was no significant difference in symptom recovery time between groups.
risk of hospitalization, 100% higher, RR 2.00, p = 1.00, treatment 2 of 30 (6.7%), control 1 of 30 (3.3%).
risk of no recovery, 11.1% lower, RR 0.89, p = 0.47, treatment 24 of 30 (80.0%), control 27 of 30 (90.0%), NNT 10, day 7.
risk of no viral clearance, 37.1% lower, RR 0.63, p = 0.10, treatment mean 7.0 (±6.2) n=30, control mean 4.4 (±5.9) n=30, relative Ct reduction, day 4.
risk of no viral clearance, 25.0% lower, RR 0.75, p = 0.06, treatment mean 11.6 (±5.9) n=30, control mean 8.7 (±5.6) n=30, relative Ct reduction, day 7.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Parienti et al., 31 Aug 2021, Double Blind Randomized Controlled Trial, France, peer-reviewed, median age 42.0, 15 authors, study period 20 November, 2020 - 19 March, 2021, this trial uses multiple treatments in the treatment arm (combined with emtricitabine) - results of individual treatments may vary, trial NCT04685512 (history) (AR0-CORONA). Contact: parienti-jj@chu-caen.fr.
Effect of Tenofovir Disoproxil Fumarate and Emtricitabine on nasopharyngeal SARS-CoV-2 viral load burden amongst outpatients with COVID-19: A pilot, randomized, open-label phase 2 trial
Jean-Jacques Parienti, Thierry Prazuck, Laure Peyro-Saint-Paul, Anna Fournier, Cécile Valentin, Sylvie Brucato, Renaud Verdon, Aymeric Sève, Mathilda Colin, Fabien Lesne, Jérome Guinard, Meriadeg Ar Gouilh, Julia Dina, Astrid Vabret, Laurent Hocqueloux
eClinicalMedicine, doi:10.1016/j.eclinm.2021.100993
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 2À7) 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 3À5) 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.
Supplementary materials Supplementary material associated with this article can be found in the online version at doi:10.1016/j.eclinm.2021.100993.
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