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Trial Finds Neither NTX nor SOF/DCV Can Prevent SARS-CoV-2
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AIDS 2022, July 29-August 2, Montreal
Mark Mascolini
Hopes that a readily available and reasonably safe medication can prevent infection with SARS-CoV-2, which causes COVID-19, got upended in a large clinical trial in South Africa [1]. Neither nitazoxanide (NTX) nor sofosbuvir/daclatasvir (SOF/DCV) proved effective in blocking infection with the novel coronavirus in the randomized COVER trial [1]. Compared with no intervention, incidence rate ratios with either prophylaxis fell far wide of the mark to indicate efficacy.
NTX, a broad-spectrum thiazolide antiparasitic agent used to treat diarrhea caused by Cryptosporidium parvum and Giardia duodenalis [2], has activity against SARS-CoV-2 and favorable pharmacokinetics. Earlier research hinted that SOF/DCV may also thwart SARS-CoV-2 [3,4].
Researchers from the University of the Witwatersrand, the University of Liverpool, and other centers randomized healthcare workers and others at high risk for SARS-CoV-2 infection in a 1-1-1 ratio to 500 mg of NTX twice daily for 1 week then 1000 mg twice daily, to SOF/DCV at 400/60 mg daily, or to standard prevention advice. Every 4 weeks participants had antibody and PCR testing for the coronavirus. The primary endpoint was a positive SARS-CoV-2 PCR and/or positive serology 7 or more days after randomization, regardless of COVID symptoms. The researchers used a Poisson regression model to estimate incidence rate ratios comparing either treatment arm with the advice-only control arm.
The trial enrolled 828 people from December 2020 to January 2022. Median age in all three study arms was 24 and about 5% were older than 50. About half of participants were women and almost everyone was black. Just under half of enrollees were university or college students, and most of the rest were healthcare workers.
Testing confirmed COVID-19 infection in 100 people taking NTX (2234 cases per 1000 person-years), 87 people taking SOF/DCV (2125 cases per 1000 person-years), and 111 in the control group (1849 cases per 1000 person-years). Compared with the control arm, the incidence rate ratio for confirmed symptomatic COVID-19 was 0.83 (95% confidence interval 0.50 to 1.40) with NTX and 0.71 (95% confidence interval 0.41 to 1.25) with SOF/DCV. Results met criteria for futility.
Grade 3 or worse adverse events excluding COVID-19 numbered 1 in the NTX group, 2 in the SOF/DCV group, and 4 in the control group. Respective numbers of serious adverse events excluding COVID-19 were 1, 1, and 1.
The researchers noted that other drug candidates are being tested to prevent transmission of SARS-CoV-2, and they believe the search for an effective agent should remain a priority.
References
1. Sokhela S, Bosch B, Hill A, et al. Randomized clinical trial of nitazoxanide or sofosbuvir/daclatasvir for the prevention of SARS CoV-2 infection. AIDS 2022, July 29-August 2, Montreal. Abstract EPC038.
2. NIH. COVID-19 treatment guidelines. Nitazoxanide. https://www.covid19treatmentguidelines.nih.gov/therapies/antiviral-therapy/nitazoxanide/
3. Roozbeh F, Saeedi M, Alizadeh-Navaei R, et al. Sofosbuvir and daclatasvir for the treatment of COVID-19 outpatients: a double-blind, randomized controlled trial. 2021;76:753-757. doi: 10.1093/jac/dkaa501.
4. Simmons B, Wentzel H, Mobarak S, et al. Sofosbuvir/daclatasvir regimens for the treatment of COVID-19: an individual patient data meta-analysis. J Antimicrob Chemother. 2021;76:286-291. doi: 10.1093/jac/dkaa418.
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