Large variability in plasma efavirenz concentration in Papua New Guinea HIV/AIDS patients associated with high frequency of CYP2B6 516T allele

Abstract Papua New Guinea (PNG) has a high HIV/AIDS prevalence and very high frequency of the CYP2B6 c.516G>T (rs3745274) variant. We have conducted the first investigation of the impact of c.516G>T and patient demographics on plasma efavirenz (EFV) and 8‐hydroxyefavirenz (8OH‐EFV) concentrati...

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Autores principales:	Natália Bordin Andriguetti, Helena Katherina Van Schalkwyk, Daniel Thomas Barratt, Joseph Tucci, Paul Pumuye, Andrew Alexander Somogyi
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/818b10c574c442b1bcc7a8e25c5d37ad
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spelling	oai:doaj.org-article:818b10c574c442b1bcc7a8e25c5d37ad2021-11-19T17:51:35ZLarge variability in plasma efavirenz concentration in Papua New Guinea HIV/AIDS patients associated with high frequency of CYP2B6 516T allele1752-80621752-805410.1111/cts.13120https://doaj.org/article/818b10c574c442b1bcc7a8e25c5d37ad2021-11-01T00:00:00Zhttps://doi.org/10.1111/cts.13120https://doaj.org/toc/1752-8054https://doaj.org/toc/1752-8062Abstract Papua New Guinea (PNG) has a high HIV/AIDS prevalence and very high frequency of the CYP2B6 c.516G>T (rs3745274) variant. We have conducted the first investigation of the impact of c.516G>T and patient demographics on plasma efavirenz (EFV) and 8‐hydroxyefavirenz (8OH‐EFV) concentrations, metabolic ratio (8OH‐EFV/EFV) (MR), and their association with adverse effects, in PNG patients with HIV/AIDS. For 156 PNG patients with HIV/AIDS taking EFV 600 mg/day (for 3–156 months), plasma EFV and 8OH‐EFV concentrations were quantified, CYP2B6 c.516G>T genotyped, and demographic and self‐reported adverse effects data recorded. Genotype differences in EFV and 8OH‐EFV concentrations, MR, and percent within therapeutic range (1000–4000 ng/ml) were examined, in addition to EFV and 8OH‐EFV concentration differences between patients experiencing adverse effects. CYP2B6 c.516T allele frequency was 53%. Plasma EFV (p < 0.0001), 8OH‐EFV (p < 0.01), and MR (p < 0.0001) differed significantly between genotypes, with genotype explaining 38%, 10%, and 50% of variability, respectively. Plasma EFV concentrations were significantly higher in T/T (median = 5168 ng/ml) than G/G (1036 ng/ml, post hoc p < 0.0001) and G/T (1502 ng/ml, p < 0.0001) genotypes, with all patients above therapeutic range (n = 23) being T/T genotype (p < 0.0001). EFV and 8OH‐EFV concentrations were not significantly higher in patients experiencing adverse effects. In PNG HIV/AIDS population where the 516T frequency is very high, it explains a substantial portion of variability (38%) in EFV disposition; however, at least for the patients receiving EFV long term, this does not translate into significant side effects.Natália Bordin AndriguettiHelena Katherina Van SchalkwykDaniel Thomas BarrattJoseph TucciPaul PumuyeAndrew Alexander SomogyiWileyarticleTherapeutics. PharmacologyRM1-950Public aspects of medicineRA1-1270ENClinical and Translational Science, Vol 14, Iss 6, Pp 2521-2531 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270
spellingShingle	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270 Natália Bordin Andriguetti Helena Katherina Van Schalkwyk Daniel Thomas Barratt Joseph Tucci Paul Pumuye Andrew Alexander Somogyi Large variability in plasma efavirenz concentration in Papua New Guinea HIV/AIDS patients associated with high frequency of CYP2B6 516T allele
description	Abstract Papua New Guinea (PNG) has a high HIV/AIDS prevalence and very high frequency of the CYP2B6 c.516G>T (rs3745274) variant. We have conducted the first investigation of the impact of c.516G>T and patient demographics on plasma efavirenz (EFV) and 8‐hydroxyefavirenz (8OH‐EFV) concentrations, metabolic ratio (8OH‐EFV/EFV) (MR), and their association with adverse effects, in PNG patients with HIV/AIDS. For 156 PNG patients with HIV/AIDS taking EFV 600 mg/day (for 3–156 months), plasma EFV and 8OH‐EFV concentrations were quantified, CYP2B6 c.516G>T genotyped, and demographic and self‐reported adverse effects data recorded. Genotype differences in EFV and 8OH‐EFV concentrations, MR, and percent within therapeutic range (1000–4000 ng/ml) were examined, in addition to EFV and 8OH‐EFV concentration differences between patients experiencing adverse effects. CYP2B6 c.516T allele frequency was 53%. Plasma EFV (p < 0.0001), 8OH‐EFV (p < 0.01), and MR (p < 0.0001) differed significantly between genotypes, with genotype explaining 38%, 10%, and 50% of variability, respectively. Plasma EFV concentrations were significantly higher in T/T (median = 5168 ng/ml) than G/G (1036 ng/ml, post hoc p < 0.0001) and G/T (1502 ng/ml, p < 0.0001) genotypes, with all patients above therapeutic range (n = 23) being T/T genotype (p < 0.0001). EFV and 8OH‐EFV concentrations were not significantly higher in patients experiencing adverse effects. In PNG HIV/AIDS population where the 516T frequency is very high, it explains a substantial portion of variability (38%) in EFV disposition; however, at least for the patients receiving EFV long term, this does not translate into significant side effects.
format	article
author	Natália Bordin Andriguetti Helena Katherina Van Schalkwyk Daniel Thomas Barratt Joseph Tucci Paul Pumuye Andrew Alexander Somogyi
author_facet	Natália Bordin Andriguetti Helena Katherina Van Schalkwyk Daniel Thomas Barratt Joseph Tucci Paul Pumuye Andrew Alexander Somogyi
author_sort	Natália Bordin Andriguetti
title	Large variability in plasma efavirenz concentration in Papua New Guinea HIV/AIDS patients associated with high frequency of CYP2B6 516T allele
title_short	Large variability in plasma efavirenz concentration in Papua New Guinea HIV/AIDS patients associated with high frequency of CYP2B6 516T allele
title_full	Large variability in plasma efavirenz concentration in Papua New Guinea HIV/AIDS patients associated with high frequency of CYP2B6 516T allele
title_fullStr	Large variability in plasma efavirenz concentration in Papua New Guinea HIV/AIDS patients associated with high frequency of CYP2B6 516T allele
title_full_unstemmed	Large variability in plasma efavirenz concentration in Papua New Guinea HIV/AIDS patients associated with high frequency of CYP2B6 516T allele
title_sort	large variability in plasma efavirenz concentration in papua new guinea hiv/aids patients associated with high frequency of cyp2b6 516t allele
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/818b10c574c442b1bcc7a8e25c5d37ad
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Large variability in plasma efavirenz concentration in Papua New Guinea HIV/AIDS patients associated with high frequency of CYP2B6 516T allele

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