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Role of Cytochrome P450 2B6 Pharmacogenomics in Determining Efavirenz‐Mediated Central Nervous System Toxicity, Treatment Outcomes, and Dosage Adjustments in Patients with Human Immunodeficiency Virus Infection
Author(s) -
Vo Teresa T.,
Varghese Gupta Sheeba
Publication year - 2016
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.1852
Subject(s) - efavirenz , cyp2b6 , medicine , pharmacology , discontinuation , adverse effect , stavudine , pharmacogenomics , emtricitabine , immunology , viral load , human immunodeficiency virus (hiv) , antiretroviral therapy , cytochrome p450 , cyp3a4 , metabolism
For treatment‐naive patients with human immunodeficiency virus infection, efavirenz ( EFV ), together with tenofovir and emtricitabine, was once widely prescribed given its efficacy and ease of administration in a combination pill. However, the high rate of central nervous system (CNS) toxicities from EFV prompted the U.S. Department of Health and Human Services to move the EFV ‐based regimen from the recommended to the alternative category. For patients who do meet the criteria for newer recommended antiretroviral treatments, EFV is a viable option and often the mainstay of treatment outside the United States because newer antiretroviral treatments are more expensive. CNS toxicity occurring with the recommended standard dose of EFV remains a challenge and may in part be attributable to polymorphisms in cytochrome P450 ( CYP ) 2B6, the enzyme involved in the major metabolic pathway for converting EFV to inactive metabolites. Functionally deficient alleles of CYP 2B6 such as CYP 2B6*6 , *18 , and *22 may be responsible for significantly higher therapeutic concentrations of EFV at a standard dose of 600 mg/day. We conducted a thorough review of the reported studies to elucidate the relationship between polymorphisms in CYP 2B6 with adverse events and treatment response, including virologic suppression, immunologic response, resistance, and discontinuation of treatment. Compelling evidence exists to support the case for CYP 2B6 genotype–guided EFV therapy while acknowledging the need for prospective controlled clinical trials to evaluate its clinical utility.