Differences in genetic variants in lopinavir disposition among HIV-infected Bantu Africans

Bafokeng Mpeta; Elizabeth Kampira; Sandra Castel; Keleabetswe L Mpye; Nyarai D Soko; Lubbe Wiesner; Peter Smith; Michelle Skelton; Miguel Lacerda; Collet Dandara

doi:10.2217/pgs.16.14

Differences in genetic variants in lopinavir disposition among HIV-infected Bantu Africans

Pharmacogenomics. 2016 May;17(7):679-90. doi: 10.2217/pgs.16.14. Epub 2016 May 4.

Affiliations

¹ 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.
² Malawi College of Health Sciences, University of Malawi, Blantyre, Malawi.
³ Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa.
⁴ Department of Statistical Sciences, Faculty of Science, University of Cape Town, South Africa.

PMID: 27142945
DOI: 10.2217/pgs.16.14

Abstract

Introduction: 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.

Materials & methods: Eighty-six HIV-positive participants on ritonavir (LPV/r) were genetically characterized and LPV plasma concentration determined.

Results & discussion: 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.

Conclusion: These findings highlight the need to include African groups in genomics research to identify variants of pharmacogenomics significance.

Keywords: ABCC2; Africa; CYP3A4/5; SLCO1B1; antiretroviral therapy; lopinavir; pharmacogenetics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Anti-HIV Agents / blood*
Anti-HIV Agents / pharmacokinetics
Anti-HIV Agents / therapeutic use
Black People / genetics
Cross-Sectional Studies
Cytochrome P-450 CYP3A / genetics
Cytochrome P-450 CYP3A / metabolism
Ethnicity / genetics
Female
HIV Infections / drug therapy*
HIV Infections / genetics*
HIV Infections / metabolism
Humans
Liver-Specific Organic Anion Transporter 1 / genetics
Liver-Specific Organic Anion Transporter 1 / metabolism
Lopinavir / blood*
Lopinavir / pharmacokinetics
Lopinavir / therapeutic use
Male
Multidrug Resistance-Associated Protein 2
Multidrug Resistance-Associated Proteins / genetics
Multidrug Resistance-Associated Proteins / metabolism
Pharmacogenomic Variants*
Polymorphism, Single Nucleotide
Young Adult

Substances

ABCC2 protein, human
Anti-HIV Agents
Liver-Specific Organic Anion Transporter 1
Multidrug Resistance-Associated Protein 2
Multidrug Resistance-Associated Proteins
SLCO1B1 protein, human
Lopinavir
CYP3A5 protein, human
Cytochrome P-450 CYP3A
CYP3A4 protein, human