The target sample size was not met. Our findings are compatible with both benefit and harm of pre-exposure prophylaxis with TDF/FTC and HCQ, alone or in combination, compared with placebo.
EPICOS is a double-blind, placebo-controlled randomized trial conducted in Spain, Bolivia, and Venezuela. Healthcare workers with negative SARS-CoV-2 IgM/IgG test were randomly assigned to: daily TDF/FTC plus HCQ for 12 weeks, TDF/FTC plus HCQ placebo, HCQ plus TDF/FTC placebo and TDF/FTC placebo plus HCQ placebo. Randomization was performed in groups of four. Primary outcome was laboratory-confirmed, symptomatic COVID-19. We also studied any (symptomatic or asymptomatic) COVID-19. We compared group-specific 14-week risks via differences and ratios with 95% confidence intervals (CI).
Of 1002 individuals screened, 926 (92.4%) were eligible and there were 14 cases of symptomatic COVID-19: 220 were assigned to the TDF/FTC plus HCQ group (3 cases), 231 to the TDF/FTC placebo plus HCQ group (3 cases), 233 to the TDF/FTC plus HCQ placebo group (3 cases), and 223 to the double placebo group (5 cases). Compared with the double placebo group, 14-week risk ratios (95% CI) of symptomatic COVID-19 were 0.39 (0.00, 1.98) for TDF+HCQ, 0.34 (0.00, 2.06) for TDF, and 0.49 (0.00, 2.29) for HCQ. Corresponding risk ratios of any COVID-19 were 0.51 (0.21, 1.00) for TDF+HCQ, 0.81 (0.44, 1.49) for TDF, and 0.73 (0.41, 1.38) for HCQ. Adverse events were generally mild.
To assess the effect of hydroxychloroquine (HCQ) and Tenofovir disoproxil fumarate/Emtricitabine (TDF/FTC) as pre-exposure prophylaxis on COVID-19 risk.
Polo R, García-Albéniz X, Terán C, Morales M, Rial-Crestelo D, Garcinuño MA, García Del Toro M, Hita C, Gómez-Sirvent JL, Buzón L, Díaz de Santiago A, Pérez Arellano JL, Sanz J, Bachiller P, Martínez Alfaro E, Díaz-Brito V, Masiá M, Hernández-Torres A, Guerra J, Santos J, Arazo P, Muñoz L, Arribas JR, Martínez de Salazar P, Moreno S, Hernán MA, Del Amo J, , , Del Amo J, Rosa Polo, Moreno S, Berenguer J, Martínez E, Hernán M, Martínez de Salazar P, García de Albéniz X, , , , . (2022). Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo controlled randomized trial in healthcare workers. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases