Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens

Wyen, Christoph; Hendra, Heidy; Siccardi, Marco; Platten, Martin; Jaeger, Hans; Harrer, Thomas; Eßer, Stefan; Bogner, Johannes R.; Bieniek, B; Rockstroh, Juergen; Hoffmann, Christian; Stoehr, Albrecht; Michalik, Claudia; Dlugay, Verena; Jetter, Alexander; Knechten, Heribert; Klinker, Hartwig; Skaletz‐Rorowski, Adriane; Fätkenheuer, Gerd; Egan, Deirdre; Back, David; Owen, Andrew; Dupke, S; Carganico, A; Baumgarten, Axel; Koeppe, S; Kreckel, Peter; Lauenroth-Mai, Elke; Schlote, Frank; Schuler, Christoph; Freiwald, Matthias; Rausch, Michael; Gölz, Jörg; Moll, A; Zeitz, Martin; Brockmeyer, Norbert H.; Hower, Martin; Reuter, Stefan; Staszewski, Schlomo; Plettenberg, Andreas; Fenske, Stefan; Buhk, Thomas; Stellbrink, Hans‐Jürgen; Schmidt, Reinhold E.; Kuhlmann, B; Mosthaf, Franz; Rieke, A.; Scholten, Stefan; Jaegel-Guedes, Eva; R, Volkert; Becker, Werner J.; Hartl, Helmut; Mutz, Antonius; Ulmer, Albrecht; Frietsch, Bernhard; Müller, Markus

doi:10.1093/jac/dkr272

Cited by 92 publications

(62 citation statements)

References 38 publications

(21 reference statements)

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“…Citation with higher plasma EFV concentrations and its toxicity, which could result in an early discontinuation of antiretroviral therapy [16][17][18]. These values are similar to the results of Uttayamakul et al (38.46%, 47.69%, 13.85%) [19].…”

Section: Cyp 2b6 Genetic Variationssupporting

confidence: 76%

Relationship between Efavirenz plasma concentrations and CYP2B6 Polymorphism in HIV/TB co-infected Africans taking rifampicin in the treatment Antituberculosis at Abidjan.

Djadji¹

2015

Clin Exp Pharmacol

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Aim: To investigate polymorphisms cytochrome 2 B6 and concomitant rifampicin use on the plasma concentration of Efavirenz 600 mg vs. 800 mg on HIV-infected Ivoirians.Methods: Consenting African patients with TB and HIV have received antiretroviral therapy including Efavirenz 600 and 800 mg, with rifampicin were observed. Efavirenz exposure was performed by HPLC MS-MS and Fluorimetric 5' nuclease genotyping Assay (Atman Assays. Applied Biosystems Foster City, CA, USA) was used to genetic determination.Results: 19 randomized patients undergone genotyping, the median age was 34 years [30][31][32][33][34][35][36][37][38][39][40][41], 09 (47%) of women, the median weight was 55 kg, with extremes [49][50][51][52][53][54][55][56][57][58][59][60][61][62], the rate basic of CD4 were 173/mm 3 . The viral load was 6.10 log10 in basic (5.66 -6.42), the Akan ethnic group was essential in our sample with 10 (52.65%), 04 (21.1%) patients were alcoholics. GG (47.370%), GT (31.58%) and TT (21.05%). Efavirenz 600 mg plasma concentration and genetic polymorphism showed no significative difference (P-value > 0.05). Also Efavirenz 800 Plasma concentration and genetic polymorphism showed no significative difference (P-value > 0.05). Therapeutic Drugs monitoring of Efavirenz 600 and 800 (C min , C max ) in VIH/TB coinfected patients receiving Rifampicin stratified by CYP 2B6 c.516 ^T genotype during the time Week 4, Week 12, Week 24 by inter-series comparison don't show any significant difference P value Kruskal Wallis > 0.05. Conclusion:Our study showed that the polymorphism does not alter significantly the values of concentrations, even if they remain well above the normal value on Caucasian patients. Others studies should be conducted to better assess the real impact of polymorphism on the plasma concentrations of Efavirenz in black.

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Section: Cyp 2b6 Genetic Variationssupporting

confidence: 76%

Relationship between Efavirenz plasma concentrations and CYP2B6 Polymorphism in HIV/TB co-infected Africans taking rifampicin in the treatment Antituberculosis at Abidjan.

Djadji¹

2015

Clin Exp Pharmacol

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“…[69,70] In a limited sample size study CYP2B6 slow metabolizing children had higher CSF nevirapine concentrations than fast metabolizers. [71] In the aforementioned study on darunavir CSF concentrations a borderline association was found between polymorphisms in the SLCO1A2 gene (encoding for OAT1A2) and CSF concentrations.…”

Section: Transporters and Pharmacogeneticsmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Antiretrovirals in the Central Nervous System

2014

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“…Higher rates of neuropsychiatric disorders in patients of African origin have been reported to be linked with the increased serum levels of efavirenz [8,9]. It is postulated that the defective CYP2B6 G516T variant allele, which is common in African population, impairs the efavirenz metabolism, thus increasing the efavirenz plasma concentrations, thereby leading to toxicity [10,11].…”

Section: Introductionmentioning

confidence: 99%

Predictors of Sleep Disorders among HIV Out-Patients in a Tertiary Hospital

Bisong¹,

Williams²,

Okpa³

et al. 2017

Recent Advances in Biology and Medicine

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Human immunodeficiency virus (HIV)-infected individuals have been shown to have a high prevalence of sleep disturbances. Both the effects of the virus and the antiretroviral drugs may cause sleep disturbances. We sought to determine the prevalence and predictors of sleep disorders among HIV seropositive adult subjects presenting at an outpatient hospital setting. One hundred and fifty six subjects were recruited for the study by using a sleep disorder screening questionnaire. The mean ages of the participants were 38.7 6 9.23 and 39.5 6 9.23 for those with and those without sleep disorder, respectively. The prevalence rate of sleep disorders was 46.2%. Elevated systolic blood pressure, lower CD4 count levels, and being on the highly active antiretroviral therapy combination TDF/3TC/ATZ/lpvr were associated with sleep disorders. The high prevalence rate observed necessitates routine screening for sleep disorders among HIV/AIDs patients.

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Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens

Abstract: These data indicate that genetic variability in CYP2B6 and CAR contributes to early treatment discontinuation for efavirenz-based antiretroviral regimens. Further studies are now required to define the clinical utility of these associations.

Cited by 92 publications

References 38 publications

Relationship between Efavirenz plasma concentrations and CYP2B6 Polymorphism in HIV/TB co-infected Africans taking rifampicin in the treatment Antituberculosis at Abidjan.

Relationship between Efavirenz plasma concentrations and CYP2B6 Polymorphism in HIV/TB co-infected Africans taking rifampicin in the treatment Antituberculosis at Abidjan.

Pharmacokinetics and Pharmacodynamics of Antiretrovirals in the Central Nervous System

Predictors of Sleep Disorders among HIV Out-Patients in a Tertiary Hospital

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