Treatment with tenofovir reduced the risk of severe COVID-19 infection among patients with chronic hepatitis B virus (HBV), a researcher reported.

In the database study of adults with HBV already on tenofovir (Biktarvy) or entecavir at 28 Spanish hospitals, patients on tenofovir had a 6% lower risk of developing severe COVID-19 versus 36% of those on entecavir (P<0.01), according to Beatriz Mateos Muñoz, PhD, of the Hospital Universitario Ramón y Cajal at the University of Alcalá in Madrid.

The risk of being admitted to the ICU was also lower at 0% among those on tenofovir therapy and 10% among those on entecavir (P=0.001). In addition, 3% of patients on tenofovir required ventilatory support versus 20% on entecavir (P<0.01). The average days in hospital with COVID-19 infection was 3.1 versus 10.8, respectively (P<0.01), while rate of death was 1.5% versus 10%, respectively (P=0.08). she said during a press conference at the European Association for the Study of the Liver (EASL) virtual meeting.

“Our results conclude that tenofovir seems to share a protective effect from severe COVID-19 in patients with chronic hepatitis B virus infection,” she said.

But David Bernstein, MD, of the Sandra Atlas Bass Center for Liver Diseases at Northwell Health in Manhasset, New York, expressed reservations about the study to MedPage Today.

“I am concerned by their conclusion for the following reasons,” he said. “Firstly, the sample size is too small to be clinically meaningful. Secondly, and more importantly, the group treated with entecavir had significantly higher rates of comorbidities…which have all been shown to increase the risk of adverse outcomes from COVID infection.”

“I believe that the reason patients on entecavir had a worse outcome from their COVID-19 infection was their underlying comorbid conditions [and had] nothing to do with hepatitis B,” stated Bernstein, who was not involved in the study.

During the EASL press conference, Munoz hypothesized that tenofovir’s activity against the SARS-CoV-2 polymerase enzyme, or more general anti-inflammatory or immunomodulatory effects, could be a reason why the drug worked so well in these patients.

Muñoz explained that, early in 2020, she saw HIV patients who were treated with antiretroviral regimens, including tenofovir, and they presented with less incidence, as well as less severity of COVID-19.

“The aim of our study was to analyze the severity and the incidence of COVID-19 on chronic HBV patients on treatment with tenofovir or entecavir and also to do a comparison between both therapies,” she stated.

Muñoz and colleagues identified 4,736 patients with HBV, 2.5% of whom had HBV and COVID-19, from February 2020 through November 2020. COVID-19 infection was defined by a positive PCR test, and severe infection by the presence of bilateral severe pneumonia, acute respiratory distress syndrome, sepsis, or septic shock.

Overall, 67 patients were treated with tenofovir and 50 patients with entecavir. For patients with HBV and COVID-19, 35% were hospitalized, 4.3% were admitted to the ICU, and 5.1% died.

Compared with patients on tenofovir, those on entecavir had significantly greater rates of obesity, diabetes, ischemic cardiopathy, and arterial hypertension, according to the authors. There was a trend for greater severity of advanced fibrosis in the entecavir patients. The risk of infection with COVID-19 was similar among the two groups, but the risk of severe complications was greater among the patients on entecavir, Muñoz reported.

In the adjusted analysis that considered age, sex, obesity, comorbidities and fibrosis stage, treatment with tenofovir was associated with an 83% relative risk reduction of contracting severe COVID-19 (adjusted OR 0.17, 95%CI 0.04-0.67, P=0.01), according to the authors.