Fowotade, A.Bamidele, F.Egbetola, B.Fagbamigbe, A. F.Adeagbo, B. A.Adefuye, B. O.Olagunoye, A.Ojo, T. O.Adebiyi, A. O.Olagunju, O. I.Ladipo, O. T.Akinloye, A.Onayade, A.Bolaji, O. O.Rannard, S.Happi, C.Owen, A.Olagunju, A.2026-03-052022-092296-858Xui_art_fowotade_randomized_2022Frontiers in Medicine 9(956123), pp. 1-12https://repository.ibadanedu.com/handle/123456789/12930Background: The nitazoxanide plus atazanavir/ritonavir for COVID-19 (NACOVID) trial investigated the efficacy and safety of repurposed nitazoxanide combined with atazanavir/ritonavir for COVID-19. Methods: This is a pilot, randomized, open-label multicenter trial conducted in Nigeria. Mild to moderate COVID-19 patients were randomly assigned to receive standard of care (SoC) or SoC plus a 14-day course of nitazoxanide (1,000 mg b.i.d.) and atazanavir/ritonavir (300/100 mg od) and followed through day 28. Study endpoints included time to clinical improvement, SARS-CoV-2 viral load change, and time to complete symptom resolution. Safety and pharmacokinetics were also evaluated (ClinicalTrials.gov ID: NCT04459286). Results: There was no difference in time to clinical improvement between the SoC (n = 26) and SoC plus intervention arms (n = 31; Cox proportional hazards regression analysis adjusted hazard ratio, aHR = 0.898, 95% CI: 0.492–1.638, p = 0.725). No difference was observed in the pattern of saliva SARS-CoV- 2 viral load changes from days 2–28 in the 35% of patients with detectable virus at baseline (20/57) (aHR = 0.948, 95% CI: 0.341–2.636, p = 0.919). There was no significant difference in time to complete symptom resolution (aHR = 0.535, 95% CI: 0.251–1.140, p = 0.105). Atazanavir/ritonavir increased tizoxanide plasma exposure by 68% and median trough plasma concentration was 1,546 ng/ml (95% CI: 797–2,557), above its putative EC90 in 54% of patients. Tizoxanide was undetectable in saliva. Conclusion: Nitazoxanide co-administered with atazanavir/ritonavir was safe but not better than standard of care in treating COVID-19. These findings should be interpreted in the context of incomplete enrollment (64%) and the limited number of patients with detectable SARS-CoV-2 in saliva at baseline in this trial.enCOVID-19SARS-CoV-2nitazoxanide (NTZ)atazanavir/ritonavirpharmacokineticsArticle