title: Differences in genetic variants in lopinavir disposition among HIV-infected Bantu Africans.
abstract: Variability in lopinavir (LPV) plasma concentration among patients could be due to genetic polymorphisms. This study set to evaluate significance of variants in CYP3A4/5, SLCO1B1 and ABCC2 on LPV plasma concentration among African HIV-positive patients.
  
  
  
  Eighty-six HIV-positive participants on ritonavir (LPV/r) were genetically characterized and LPV plasma concentration determined.
  
  
  
  LPV plasma concentrations differed >188-fold (range 0.0206-38.6 µg/ml). Both CYP3A4*22 and SLCO1B1 rs4149056G (c.521C) were not observed in this cohort. CYP3A4*1B, CYP3A5*3, CYP3A5*6 and ABCC2 c.1249G>A which have been associated with LPV plasma concentration, showed no significant association.
  
  
  
  These findings highlight the need to include African groups in genomics research to identify variants of pharmacogenomics significance.
authors.affiliation: Division of Human Genetics, Department of Pathology (formerly Clinical Laboratory Sciences) & Institute of Infectious Disease & Molecular Medicine, Faculty of Health Sciences, University of Cape Town, South Africa.
authors.forename: Bafokeng
authors.initials: B
authors.lastname: Mpeta
authors.affiliation: Malawi College of Health Sciences, University of Malawi, Blantyre, Malawi.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kampira
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa.
authors.forename: Sandra
authors.initials: S
authors.lastname: Castel
authors.affiliation: Division of Human Genetics, Department of Pathology (formerly Clinical Laboratory Sciences) & Institute of Infectious Disease & Molecular Medicine, Faculty of Health Sciences, University of Cape Town, South Africa.
authors.forename: Keleabetswe L
authors.initials: KL
authors.lastname: Mpye
authors.affiliation: Division of Human Genetics, Department of Pathology (formerly Clinical Laboratory Sciences) & Institute of Infectious Disease & Molecular Medicine, Faculty of Health Sciences, University of Cape Town, South Africa.
authors.forename: Nyarai D
authors.initials: ND
authors.lastname: Soko
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa.
authors.forename: Lubbe
authors.initials: L
authors.lastname: Wiesner
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa.
authors.forename: Peter
authors.initials: P
authors.lastname: Smith
authors.affiliation: Division of Human Genetics, Department of Pathology (formerly Clinical Laboratory Sciences) & Institute of Infectious Disease & Molecular Medicine, Faculty of Health Sciences, University of Cape Town, South Africa.
authors.forename: Michelle
authors.initials: M
authors.lastname: Skelton
authors.affiliation: Department of Statistical Sciences, Faculty of Science, University of Cape Town, South Africa.
authors.forename: Miguel
authors.initials: M
authors.lastname: Lacerda
authors.affiliation: Division of Human Genetics, Department of Pathology (formerly Clinical Laboratory Sciences) & Institute of Infectious Disease & Molecular Medicine, Faculty of Health Sciences, University of Cape Town, South Africa.
authors.forename: Collet
authors.initials: C
authors.lastname: Dandara
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D044383:Black People / Q000235:genetics; D003430:Cross-Sectional Studies; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D005006:Ethnicity / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics / Q000378:metabolism; D061466:Lopinavir / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D000071184:Pharmacogenomic Variants; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D051544:Cytochrome P-450 CYP3A; D027381:Liver-Specific Organic Anion Transporter 1; D061466:Lopinavir; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human; C503999:SLCO1B1 protein, human; C510164:CYP3A5 protein, human; C510163:CYP3A4 protein, human
keywords: ABCC2; Africa; CYP3A4/5; SLCO1B1; antiretroviral therapy; lopinavir; pharmacogenetics