Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: A double-blind placebo controlled randomized trial in healthcare workers

Xabier Garcia de Albeniz Martinez; Rosa Polo; X García-Albéniz; C Terán; M Morales; D Rial-Crestelo; M A Garcinuño; M García Del Toro; C Hita; J L Gómez-Sirvent; L Buzón; A Díaz de Santiago; J L Pérez Arellano; J Sanz; P Bachiller; E Martínez Alfaro; V Díaz-Brito; M Masiá; A Hernández-Torres; Jessica Prince-Guerra; Jennifer De Los Santos; P Arazo; Gabriel Lázaro-Muñoz; J R Arribas; P Martínez de Salazar; S. Boiso Moreno; M A Hernán; Julia Del Amo; Julia Del Amo; Rosa Polo; Santiago Moreno; Juan Berenguer; Esteban Martínez; Miguel A Hernán; Pablo Martínez de Salazar; Xabier Garcia de Albeniz Martinez

Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19

A double-blind placebo controlled randomized trial in healthcare workers

Polo, R., García-Albéniz, X., Terán, C., Morales, M., Rial-Crestelo, D., Garcinuño, M. A., García Del Toro, M., Hita, C., Gómez-Sirvent, J. L., Buzón, L., Díaz de Santiago, A., Pérez Arellano, J. L., Sanz, J., Bachiller, P., Martínez Alfaro, E., Díaz-Brito, V., Masiá, M., Hernández-Torres, A., Guerra, J., ... EPICOS (2023). 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, 29(1), 85-93. Advance online publication. https://doi.org/10.1016/j.cmi.2022.07.006

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Abstract

OBJECTIVES: To assess the effect of hydroxychloroquine (HCQ) and Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as pre-exposure prophylaxis on COVID-19 risk.

METHODS: 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 the following: 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% CIs.

RESULTS: 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.

DISCUSSION: 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.