Drug Interactions and Antiretroviral Drug Monitoring

Abstract

Due to the improved longevity afforded by combination antiretroviral therapy (cART), HIV-infected individuals are developing several non-AIDS related comorbid conditions. Consequently, medical management of the HIV-infected population is increasingly complex, with a growing list of potential drug-drug interactions (DDIs). This article reviews some of the most relevant and emerging potential interactions between antiretroviral medications and other agents. The most common DDIs are those involving protease inhibitors or non-nucleoside reverse transcriptase inhibitors which alter the cytochrome P450 enzyme system and/or drug transporters such as p-glycoprotein. Of note are the new agents for the treatment of chronic hepatitis C virus infection. These new classes of drugs and others drugs which are increasingly used in this patient population represent a significant challenge with regard to achieving the goals of effective HIV suppression and minimization of drug-related toxicities. Awareness of DDIs and a multidisciplinary approach are imperative in reaching these goals.

Management of lipid disorders in patients living with HIV

“…Atorvastatin co‐administration with PIs leads to moderate increases in its Area Under the Curve (AUC). The FDA has recommended avoiding the use of atorvastatin with tipranavir, using atorvastatin with caution at the lowest possible dose with lopinavir/ritonavir and not exceeding a dose of 20 milligrams of atorvastatin when co‐administered with saquinavir, fosamprenavir, or darunavir …”

“…In the case of darunavir, subjects with low functioning haplotype forms of the SLCO1B1 drug transporter gene had significantly increased pravastatin concentrations compared to those with wild‐type forms. Therefore, the darunavir package insert recommends that the lowest possible dose of pravastatin be used in patients taking darunavir …”

“…Rosuvastatin can also interact with various PIs through non‐CYP mechanisms. The FDA recommends a maximum dose of rosuvastatin 10 milligrams daily when co‐administered with boosted atazanavir or lopinavir . The combination of tipranavir with rosuvastatin should be avoided or used cautiously starting with the lowest dose possible of rosuvastatin of 5 milligrams daily due to an increase in adverse effects …”

“…Efavirenz also reduces the pravastatin AUC by 40% even though pravastatin is only minimally metabolized by CYP3A. No dose adjustment is required for pitavastatin when co‐administered with efavirenz …”

“…Fluvastatin, rosuvastatin, and pitavastatin are metabolized at least in part by CYP2C9 and co‐administration with etravirine may result in higher plasma concentrations of the statins although actual pharmacokinetic data are lacking. No dose adjustments are required when rilpivirine is co‐administered with statins …”