For patients with mild to moderate COVID-19 infection receiving standard care, the addition of either sofosbuvir/ledipasvir or nitazoxanide alone resulted in an increased rate of viral clearance, according results of a study published in the Arab Journal of Gastroenterology.
This study included adult patients from multiple centers in Egypt who were positive for COVID-19 infection via reverse-transcriptase polymerase chain reaction testing (RT-PCR) between July 2020 and October 2021. All patients received standard care and were randomly assigned to receive either sofosbuvir/ledipasvir (400/90 mg once daily), nitazoxanide (500 mg 4 times daily), or standard care alone. All patients received treatment for 14 days, and standard care comprised azithromycin for 3 days plus vitamin C and zinc supplements for the full treatment course. Included patients were those who met the World Health Organization’s definition for nonsevere COVID-19 infection and had a creatinine clearance greater than 30 mL/min with no malignancy. The primary endpoint was SARS-CoV-2 viral clearance, with viral load assessed via RT-PCR at days 5, 8, 11, and 14 following treatment initiation.
A total of 190 patients were enrolled, of whom 70 received sofosbuvir/ledipasvir, 77 received nitazoxanide, and 73 received standard care alone. The most common comorbidities included hypertension and diabetes mellitus. With the exception of the sofosbuvir/ledipasvir and nitazoxanide groups comprising populations in which more than half of the patients were women, and the standard care group comprising mostly men, no other significant demographic differences were noted among the 3 groups.
At each follow-up visit, the rate of SARS-CoV-2 viral clearance was significantly increased among patients in the 2 treatment groups compared with those in the standard care group (P <.001). Among patients who received sofosbuvir/ledipasvir, 36.9% demonstrated early viral clearance by day 5. The percentage of patients who tested negative for infection at day 14 was 83.1%, 39.7% and 19.4% among those in the sofosbuvir/ledipasvir, nitazoxanide, and standard care groups, respectively.
The only significant factors identified via Cox regression analysis for negative RT-PCR test result were treatment with either sofosbuvir/ledipasvir (hazards ratio [HR], 11.14; 95% CI, 5.923-20,923) or nitazoxanide (HR, 2.25; 95% CI, 1.13-4.46). Mild gastrointestinal-related events were reported by 4 and 10 patients in the sofosbuvir/ledipasivir and nitazoxanide groups, respectively, and no mortality outcomes or severe adverse events were observed in any group.
Study limitations included the small sample size. The researchers suggested the need for additional multicenter studies to compare the effects of different sofosbuvir-based therapies.
According to the researchers, “these drugs [were] well tolerated for the duration of therapy… [and] represent a promising, safe, and affordable treatment in the management of COVID-19.”
Medhat MA, El-Kassas M, Karam-Allah H, et al. Sofosbuvir/Ledipasvir in combination or nitazoxanide alone are safe and efficient treatments for COVID-19 infection: A randomized controlled trial for repurposing antivirals. Arab J Gastroenterol. Published online May 6, 2022. doi:10.1016/j.ajg.2022.04.005