Safety, Efficacy of Sofosbuvir Plus Daclatasvir in Patients With COVID-19

Female doctor in protective suit consoling senior patient. Elderly man with oxygen mask is lying on bed in intensive care unit during COVID-19 crisis. They are in hospital ward.
Researchers assessed efficacy and safety outcomes of patients with moderate to severe COVID-19 who received standard care alone; with sofosbuvir plus daclatasvir; or with sofosbuvir plus ravidasvir.

For patients with COVID-19, adding the antiviral agents sofosbuvir (SOF) and daclatasvir (DCV) to standard care demonstrated increased efficacy and safety, and the SOF-DCV combination decreased intensive care unit (ICU) admissions compared with standard care alone, according to results of a phase 3 study published in the Journal of Medical Virology.

SOF plus DCV is a 2-drug combination used to treat hepatitis C virus. The researchers also evaluated the combination of SOF plus ravidasvir (RDV), a pangenotypic nonstructural protein 5A inhibitor currently under clinical investigation for the treatment of adults with chronic hepatitis C virus.

Currently, only remdesivir has been validated as a COVID-19 treatment, but “[r]epurposing antiviral treatments might prove the fastest way to identify effective therapy [for COVID-19],” the researchers noted. They chose to study SOF plus DCV and SOF plus RDV because these combinations “could inhibit [2] SARS-CoV-2 replication enzymes.”

In an open-label, prospective trial, conducted between September 2020 and March 2021, researchers randomly assigned 120 patients with moderate or severe COVID-19 in a 1:1:1 fashion to receive either 10 days of treatment with standard care plus the SOF-DCV combination; standard care plus the SOF-RDV combination; or standard care alone. After 7 days of follow-up, they compared the sum symptoms at days 7 and 10, the mean change in oxygen saturation, viral negativity, and rate of ICU admission.

The combination of SOF-DCV produced a significant decrease in the number of symptoms at day 7 (P =.041) and day 10 (P =.0399). Oxygen saturation level over time improved for all groups. Compared with standard care, patients who received SOF-DCV showed significantly improved oxygen saturation at day 4. After completion of treatment on day 10, the percentage of patients with no detectable viral RNA was increased among those in the SOF-DCV group vs those who received standard care alone (46.2% vs 40.0%, odds ratio, 1.29; P =.581) but the percentages were similar for SOF‐RDV vs standard care (41.5% vs 40.0%, P =.893).

Compared with standard care, the percentage of patients admitted to an ICU was significantly decreased among those in the SOF-DCV group (7.5% vs 20.0%; P =.09) and was also decreased, though not significantly, among those in the SOF-RDV group (12.5% vs 20.0%; P =.273). Reported adverse events and mortality were significantly among patients in the SOF-DCV group vs those who received standard care alone.

Limitations of this study included its small sample size, open-label design, and lack of a placebo group. Larger, blinded, placebo-controlled trials are still needed.

The researchers concluded that their findings “highlight the promising potential of SOF‐DCV to offer an effective, safe, cost‐effective treatment option [for] COVID‐19 management among diverse populations.”

Disclosure: This study was funded by Pharco Pharmaceuticals. In addition, some author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Abbass S, Kamal E, Salama M, et al. Efficacy and safety of sofosbuvir plus daclatasvir or ravidasvir in patients with COVID-19: A randomized controlled trial. J Med Virol. Published online August 11, 2021. doi:10.1002/jmv.27264