Abstract
Objective:Efavirenz (EFV) use is associated with neuropsychiatric side effects, which may include poor neurocognitive performance. We evaluated single nucleotide polymorphisms in genes that contribute to EFV pharmacokinetics and examined them in association with EFV concentrations in plasma and hair, as well as neurocognitive performance.Design:Cross-sectional study in which adults with HIV receiving 600-mg EFV for at least 2 months were recruited and paired hair and dried blood spots (DBS) samples collected.Methods:Participants (N = 93, 70.3% female) were genotyped for seven single nucleotide polymorphisms in CYP2B6, NRII3 and ABCB1 using DBS. EFV was quantified in DBS and hair using validated liquid-chromatography-tandem-mass-spectrometry methods, with plasma EFV concentrations derived from DBS levels. Participants were also administered a neurocognitive battery of 10 tests (seven domains) that assessed total neurocognitive functioning.Results:Strong correlation (r = 0.66, P < 0.001) was observed between plasma and hair EFV concentrations. The median (interquartile range) hair EFV concentration was 6.85 ng/mg (4.56-10.93). CYP2B6 516G>T, (P < 0.001) and CYP2B6 983T>C (P = 0.001) were each associated with hair EFV concentrations. Similarly, 516G>T (P < 0.001) and 983T>C (P = 0.009) were significantly associated with plasma EFV concentration. No other genetic associations were observed. Contrary to other studies, total neurocognitive performance was significantly associated with plasma EFV concentrations (r = 0.23, P = 0.043) and 983T>C genotype (r = 0.38, P < 0.0005).Conclusion:This study demonstrated approximately three-fold and two-fold higher EFV plasma and hair concentrations, respectively, among CYP2B6 516TT compared with 516GG. Higher EFV concentrations were associated with better neurocognitive performance, requiring further study to elucidate the relationships between adherence, adverse effects and outcomes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1919-1927 |
| Number of pages | 9 |
| Journal | AIDS |
| Volume | 35 |
| Issue number | 12 |
| DOIs | |
| State | Published - Oct 1 2021 |
Funding
Research training for this publication was supported by the Fogarty International Center and National Institute of Mental Health (NIMH) of the National Institutes of Health (NIH) under award number D43TW009608, PI – Professor Babafemi Taiwo. This work is partially supported by NIAID/NIH (2RO1AI098472 and R03 AI152773, PI Gandhi).The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Keywords
- dried blood spots
- efavirenz
- hair
- neurocognitive performance
- single nucleotide polymorphisms
ASJC Scopus subject areas
- Infectious Diseases
- Immunology and Allergy
- Immunology
