The role of cytochrome P450 in antiretroviral drug interactions

Abstract

As millions of patients with HIV/AIDS are put on treatment with the highly active antiretroviral therapy (HAART), drug interactions have become a major concern for healthcare providers. The use of HAART as a combination of 3 - 4 drugs creates potential for antiretroviral (ARV) drug interactions, and this is complicated by the addition of other drugs for treatment of other ailments such as comorbid chronic conditions and/or opportunistic infections. It has been observed that most ARV drug interactions involve drugs that interact with CYP enzymes. Specifically, protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) are the most implicated in ARV drug interactions and are metabolised by CYP isoenzymes. Because PIs and NNRTIs can also inhibit and induce some of the CYP isoenzymes, they often interfere with the metabolism of several drugs eliminated by CYP isoenzymes, and the converse is true. The drug groups most implicated in CYP-mediated interactions with ARV drugs include: rifamycins; statins; antibiotics; antifungals; antiulcer drugs; contraceptives; immunosuppressant drugs; drugs for erectile dysfunction; drugs of abuse; drugs for treatment of addiction; benzodiazepines; anticonvulsants; psychotropic agents; herbal products; antiarrhythmias; antimalarials; anticoagulants; and antiasthma drugs. Unfortunately, this information is published in different resources where it may not be accessible to many, and is also liable to misinterpretation if read in isolation. Here, this information has been pooled and discussed with a hope that it will enable appropriate use in patients with HIV/AIDS. The review was confined to CYP-associated ARV drug interactions to emphasise that prevention of ARV drug interactions requires thorough knowledge of CYP function and regulation by healthcare providers.