Associations between efavirenz concentrations, pharmacogenetics, and neurocognitive performance in people living with HIV in Nigeria.

Nwogu, Jacinta N, Gandhi, Monica, Owen, Andrew ORCID: 0000-0002-9819-7651, Khoo, Saye ORCID: 0000-0002-2769-0967, Taiwo, Babafemi, Olagunju, Adeniyi ORCID: 0000-0002-6588-5749, Berzins, Baiba, Okochi, Hideaki, Tallerico, Regina, Robertson, Kevin
et al (show 1 more authors) (2021) Associations between efavirenz concentrations, pharmacogenetics, and neurocognitive performance in people living with HIV in Nigeria. AIDS (London, England), 35 (12). pp. 1919-1927.

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<h4>Objective</h4>Efavirenz use is associated with neuropsychiatric side effects, which may include poor neurocognitive performance. We evaluated single nucleotide polymorphisms (SNPs) in genes that contribute to efavirenz pharmacokinetics and examined them in association with EFV concentrations in plasma and hair, as well as neurocognitive performance.<h4>Design</h4>Cross-sectional study where adults with HIV (PWH) receiving 600 mg efavirenz for at least two months were recruited and paired hair and dried blood spots (DBS) samples collected.<h4>Methods</h4>Participants (N = 93, 70.3% female) were genotyped for 7 SNPs in CYP2B6, NRII3 and ABCB1 using DBS. Efavirenz was quantified in DBS and hair using validated liquid-chromatography-tandem-mass-spectrometry methods, with plasma efavirenz concentrations derived from DBS levels. Participants were also administered a neurocognitive battery of 10 tests (7 domains) that assessed total neurocognitive functioning.<h4>Results</h4>Strong correlation (r = 0.66, P < 0.001) was observed between plasma and hair efavirenz concentrations. The median (IQR) hair efavirenz concentration was 6.85ng/mg (4.56-10.93). CYP2B6 516G > T, (P < 0.001) and CYP2B6 983T > C (P = 0.001) were each associated with hair efavirenz concentrations. Similarly, 516G > T (P < 0.001) and 983T > C (P = 0.009) were significantly associated with plasma efavirenz concentration. No other genetic associations were observed. Contrary to other studies, total neurocognitive performance was significantly associated with plasma efavirenz concentrations (r = 0.23, P = 0.043) and 983T > C genotype (r = 0.38, P < 0.0005).<h4>Conclusion</h4>This study demonstrated approximately 3-fold and 2-fold higher efavirenz plasma and hair concentrations, respectively, among CYP2B6 516TT compared to 516GG. Higher efavirenz concentrations were associated with better neurocognitive performance, requiring further study to elucidate the relationships between adherence, adverse effects and outcomes.

Item Type: Article
Uncontrolled Keywords: dried blood spots, efavirenz, hair, neurocognitive performance, single nucleotide polymorphisms
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 12 Aug 2021 08:05
Last Modified: 18 Jan 2023 21:33
DOI: 10.1097/qad.0000000000002984
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