The hepatitis C drug Sovaldi (sofosbuvir) can adversely interact with the human immunodeficiency virus (HIV) drug Viread (tenofovir disoproxil), according to recent findings. Both drugs are manufactured and commercialized by Gilead Sciences.
Sovaldi and other direct-acting antiviral drugs that contain sofosbuvir, such as Harvoni and Epclusa, are used in the treatment of hepatitis C virus (HCV) infection. These drugs are molecules that target specific nonstructural proteins of the virus and result in disruption of viral replication and infection. They can lead to cure rates of more than 95 percent in a short period of time.
HCV patients co-infected with HIV usually receive both anti-HCV and antiretroviral therapy (for example, Viread).
However, evidence from studies have shown that sofosbuvir-containing regimens can cause liver or kidney toxicity when co-administered with Viread and anti-HIV drugs.
In the new study, Bingfang Yan, professor of biomedical and pharmaceutical sciences at the University of Rhode Island, and graduate student Yuanjun Shen, found that Sovaldi inhibits the hydrolysis (decomposition in water) of Viread, affecting the drug-activating CES-2 enzyme permanently.
“This decreases the therapeutic activation of [Viread] with implications of increased kidney toxicity,” Yan said in a news release.
“CES-2 is generally considered as a detoxification enzyme,” Yan added. “It is abundant in the liver and kidney. The enzyme (CES-2) normally breaks down through hydrolysis, activating such medicines as [Viread] or inactivating such medicines as aspirin.”
With the enzyme rendered useless by Sovaldi, Viread and similar HIV drugs cannot exert their full properties and can accumulate at levels that are toxic for patients.
“Sovaldi has become a standard of hepatitis C therapy since its approval in December 2013,” Yan said. While Sovaldi is highly effective, it is pricey, with a treatment course of 12 weeks costing $75,000 or more.
Besides the negative interaction with certain HIV therapies, the U.S. Food and Drug Administration (FDA) recently issued a warning concerning the reported link between Sovaldi and cases of hepatitis B reactivation in patients who have been infected with both hepatitis B virus (HBV) and HCV and who were being treated with Solvadi.
Yan suggested physicians should prescribe direct-acting antiviral drugs with instructions for patients to take them at different times or different routes. For instance, the HIV medication can be administered first, or through the skin; while the HCV drug can be taken orally at a later time.
More studies are required to fully assess the impact of these drugs when taken in combination, Yan said.