title: Pharmacogenetics of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in resource-limited settings: Influence on antiretroviral therapy response and concomitant anti-tubercular, antimalarial and contraceptive treatments.
abstract: The burden of human immunodeficiency virus (HIV) is mainly concentrated to resources-limited countries where the response to available antiretroviral therapy is often limited by the occurrence of toxicity or by the emergence of HIV drug resistance. Efavirenz and nevirapine are the antiretroviral drugs most prescribed in resources-limited countries as part of antiretroviral combination therapy. Their metabolism and conjugation are largely influenced by enzymatic genetic polymorphisms. The genetic variability of their metabolism could be associated to different metabolic phenotypes causing reduced patients' adherence because of toxicity or drug-drug interactions with concomitant therapies. The purpose of this review is to summarize published evidence on pharmacogenetic and pharmacokinetic aspects related to efavirenz and nevirapine, the influence of concomitant anti-tubercular, anti-malarial or contraceptive treatments, and the impact of human genetic variation and drug-drug interaction on the virologic and immunologic response to antiretroviral therapy in resources-limited countries.
authors.affiliation: Department of Public Health and Infectious Diseases, University "La Sapienza", P.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Russo
authors.affiliation: Botswana-University of Pennsylvania Partnership, P.O. Box AC 157 ACH, Gaborone, Botswana; Medical Education Partnership Laboratory, c/o Faculty of Medicine, University of Botswana, Pvt Bag 00713, Gaborone, Botswana. Electronic address: paganottig@botswana-upenn.co.bw.
authors.forename: Giacomo Maria
authors.initials: GM
authors.lastname: Paganotti
authors.affiliation: Division of Pediatrics, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Karolinska University Hospital, B57, SE-141 86, Stockholm, Sweden.
authors.forename: Sandra
authors.initials: S
authors.lastname: Soeria-Atmadja
authors.affiliation: Botswana-University of Pennsylvania Partnership, P.O. Box AC 157 ACH, Gaborone, Botswana.
authors.forename: Miriam
authors.initials: M
authors.lastname: Haverkamp
authors.affiliation: Botswana-University of Pennsylvania Partnership, P.O. Box AC 157 ACH, Gaborone, Botswana.
authors.forename: Doreen
authors.initials: D
authors.lastname: Ramogola-Masire
authors.affiliation: Department of Public Health and Infectious Diseases, University "La Sapienza", P.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vullo
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, SE-141 86, Stockholm, Sweden.
authors.forename: Lars Lennart
authors.initials: LL
authors.lastname: Gustafsson
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D000962:Antimalarials / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use; D048588:Benzoxazines / Q000493:pharmacokinetics / Q000494:pharmacology; D003270:Contraceptive Agents / Q000627:therapeutic use; D003521:Cyclopropanes; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004347:Drug Interactions; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D019829:Nevirapine / Q000493:pharmacokinetics / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D000962:Antimalarials; D000995:Antitubercular Agents; D048588:Benzoxazines; D003270:Contraceptive Agents; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D003577:Cytochrome P-450 Enzyme System; D019829:Nevirapine; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; C098320:efavirenz
keywords: Drug–drug interactions; Efavirenz; HIV; Nevirapine; Pharmacogenetics; Resource-limited countries