The relationships of ABCB1 3435C>T and CYP2B6 516G>T with high-density lipoprotein cholesterol in HIV-infected patients receiving Efavirenz.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are associated with a favorable increase in high-density lipoprotein cholesterol (HDL-c) level. Isolated studies have found a direct correlation between efavirenz (EFV) exposure and HDL-c level changes. Here we explore the impact that drug disposition variants associated with EFV exposure have on changes in HDL-c level. Seventy-six patients on first-line EFV-based regimens were genotyped for CYP2B6 516G>T and ABCB1 3435C>T. There was a 37% increase (+0.32 mmol/l, P < 0.001) in mean HDL-c level over 48 weeks, and this was univariately associated with gender (male +0.26 mmol/l, female +0.55 mmol/l; P = 0.03), ABCB1 3435C>T (CC +0.26 mmol/l, CT +0.16 mmol/l, TT +0.54 mmol/l; P(ANOVA) = 0.003) and CYP2B6 516 G>T (GG +0.27 mmol/l, GT +0.29 mmol/l, TT +0.72 mmol/l; P(ANOVA) = 0.08). There was a significant association between the cumulative number of predictive genotypes (CYP2B6 516TT or ABCB1 3435TT) and mean HDL-c level change: (group 0 +0.20 mmol/l, group 1 +0.47 mmol/l, group 2 +1.00 mmol/l; P(ANOVA) < 0.0001). These findings need to be validated in independent cohorts.
Mahungu
T W
TW
Department of HIV Medicine, Royal Free NHS Trust, London, UK. wambura@gmail.com
Nair
D
D
Smith
C J
CJ
Egan
D
D
Youle
M
M
Johnson
M A
MA
Khoo
S H
SH
Back
D J
DJ
Owen
A
A
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D048588:Benzoxazines / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D008076:Cholesterol, HDL / Q000097:blood*; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy* / Q000208:ethnology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018894:Reverse Transcriptase Inhibitors / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D012737:Sex Factors; D013997:Time Factors
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D008076:Cholesterol, HDL; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; C098320:efavirenz