Sovaldi and other hepatitis C drugs containing sofosbuvir can inhibit hydrolysis of the HIV drug Viread, irreversibly affecting the drug-activating carboxylesterase-2 enzyme, according to a letter to the editor published in Journal of Hepatology.
“This decreases the therapeutic activation of [Viread; tenofovir disoproxil, Gilead Sciences] with implications of increased kidney toxicity,” Bingfang Yan, DVM, PhD, professor of biomedical and pharmaceutical sciences in the College of Pharmacy/Academic Health Collaborative, said in a press release.
Yan and graduate student Yuanjun Shen obtained liver microsomes from 20 human donors and kidney microsomes from 12 human donors, which they pre-incubated with Sovaldi (sofosbuvir, Gilead Sciences). They then added the colorimetric substrate p-nitrophenylacetate (PNPA), and monitored hydrolysis of PNPA using a micro-plate reader. Ultimately, they found “sofosbuvir potently inhibited the hydrolysis by both liver and kidney microsomes,” and further testing showed sofosbuvir “is a potent and covalent CES-2 inhibitor.”
“CES-2 is generally considered as a detoxification enzyme,” Yan said in the press release. “It is abundant in the liver and kidney. The enzyme (CES-2) normally breaks down through hydrolysis, activating such medicines as tenofovir disoproxil or inactivating such medicines as aspirin.”
As sofosbuvir and other sofosbuvir-containing drugs are often used in combination with tenofovir disoproxil to treat patients coinfected with HIV and HCV, Yan and Shen recommended that physicians instruct patients to take these drugs at different times or via different routes of administration until clinical trials are performed to fully analyze the effects of taking them in combination. – by Adam Leitenberger
Disclosures: The researchers report no relevant financial disclosures.