Combination drugs may cause adverse events in individuals coinfected with HIV and HCV.
Hepatitis C virus (HCV) drugs may clash with HIV drugs, causing adverse events in individuals who use them together.
In a study published in the Journal of Hepatology, investigators found that the HCV drug, sofosbuvir (Sovaldi), can adversely interact with the HIV drug, tenofovir disoproxil (Viread). Both drugs are manufactured and sold by Gilead Sciences Inc.
“Sovaldi has become a standard of hepatitis C therapy since its approval in December 2013,” said investigator Bingfang Yan.
Drugs containing sofosbuvir are frequently used in combination with additional medications to combat coinfection with viruses such as HIV and hepatitis B virus (HBV). However, evidence has linked sofosbuvir-containing regimens to severe liver and kidney toxicity, or reactivation of the other virus.
In fact, earlier this year the FDA ordered placement of the agency’s most prominent warning on these drugs after study findings showed they could reactivate HBV in people coinfected with HCV.
The results of the current study showed that sofosbuvir inhibited the hydrolysis of tenofovir disoproxil, which irreversibly affected the drug-activating CES-2 enzyme.
“This decreases the therapeutic activation of tenofovir disoproxil with implications of increased kidney toxicity,” Yan said. “CES-2 is generally considered as a detoxification enzyme, it is abundant in the liver and kidney. The enzyme normally breaks down through hydrolysis, activating such medicines as tenofovir disoproxil or inactivating such medicines as aspirin.”
Unfortunately, sofosbuvir renders the enzyme useless, meaning these medications are unable to fully work, and can accumulate at toxic levels.
Yan advised that physicians prescribe the medications with instructions to take them at different times or different routes. For instance, the HIV medication can be administered first, or through the skin; and the HCV medication can be taken orally at a later time, Yan suggested.
Further clinical trials are needed to fully analyze the impact of the medications when used in combination, according to the investigators.