The Relationships of ABCB1 3435C>T and CYP2B6 516G>T With High-Density Lipoprotein Cholesterol in HIV-Infected Patients Receiving Efavirenz

• Published in: Clinical pharmacology and therapeutics Vol. 86; no. 2; pp. 204 - 211
• Main Authors: Mahungu, TW, Nair, D, Smith, CJ, Egan, D, Youle, M, Johnson, MA, Khoo, SH, Back, DJ, Owen, A
• Format: Journal Article
• Language: English
• Published: United States 01-08-2009
• Subjects: Adult; Anti-HIV Agents - blood; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Aryl Hydrocarbon Hydroxylases - genetics; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Benzoxazines - blood; Benzoxazines - pharmacology; Benzoxazines - therapeutic use; Cholesterol, HDL - blood; Cytochrome P-450 CYP2B6; Female; Genotype; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - ethnology; Humans; Male; Middle Aged; Multivariate Analysis; Oxidoreductases, N-Demethylating - genetics; Polymorphism, Single Nucleotide; Reverse Transcriptase Inhibitors - blood; Reverse Transcriptase Inhibitors - pharmacology; Reverse Transcriptase Inhibitors - therapeutic use; Sex Factors; Time Factors
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1038/clpt.2009.78

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; PANOVA = 0.003) and CYP2B6 516 G>T (GG +0.27 mmol/l, GT +0.29 mmol/l, TT +0.72 mmol/l; PANOVA = 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; PANOVA < 0.0001). These findings need to be validated in independent cohorts.
Clinical Pharmacology & Therapeutics (2009); 86, 2, 204–211 doi:10.1038/clpt.2009.78