Dose Reduction of Efavirenz: An Observational Study Describing Cost–Effectiveness, Pharmacokinetics and Pharmacogenetics

Martín, Ángel Puerto; Gómez, Amalia; García‐Berrocal, Belén; Figueroa, Salvador Cabrera; Sánchez, María Dolores Calvo; Hernández, M.V.; González-Buitrago, José Manuel; Merino, María Paz Valverde; Tovar, Carmen Bustos; Martín, Ana Cristina López; Isidoro‐García, María

doi:10.2217/pgs.14.48

Cited by 28 publications

(18 citation statements)

References 37 publications

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“…This suggests that central nervous system symptoms might decrease with lower doses. In one observational study in which doses were reduced in patients already receiving efavirenz, guided by CYP2B6 genotype and therapeutic drug monitoring, there were decreased central nervous system symptoms, continued virologic control and cost savings [20]. Economic considerations may increasingly affect ART prescribing, particularly with multiple options for initial ART with varying costs [1].…”

mentioning

confidence: 99%

Cost–Effectiveness of CYP2B6 Genotyping to Optimize Efavirenz Dosing in HIV Clinical Practice

et al. 2015

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Aims To assess the cost–effectiveness of CYP2B6 genotyping to guide efavirenz dosing for initial HIV therapy in the USA. Methods We used the Cost–Effectiveness of Preventing AIDS Complications (CEPAC) microsimulation model to project quality-adjusted life expectancy and lifetime costs (2014 US dollars) for efavirenz-based HIV therapy with or without CYP2B6 genotyping. We assumed that with genotyping 60% of patients would be eligible to receive lower doses. Results Current care without CYP2B6 genotyping has an incremental cost–effectiveness ratio >$100,000/QALY compared with genotype-guided dosing, even if lower dosing reduces efficacy. When we assumed generic efavirenz availability, conclusions were similar unless lower dosing reduces efficacy by 6% or more. Conclusion CYP2B6 genotyping can inform efavirenz dosing and decrease HIV therapy cost.

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confidence: 99%

Cost–Effectiveness of CYP2B6 Genotyping to Optimize Efavirenz Dosing in HIV Clinical Practice

et al. 2015

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“…For example, one retrospective study reported that therapeutic dose monitoring and dose reduction in 31 patients with one or two 516 T alleles from a standard 600 mg/day dose of EFV to 400 mg/day, reduced the mean EFV C min (5.7 +/−3.4 mg/l at 600 mg/day) to within therapeutic range (2.39 +/− 1.28 mg/l at 400 mg/day) [47]. The authors also report that decreasing dosage in those patients also correlated with a decrease in the percentage of patients reporting CNS adverse events (from 89.3% to 9.7%), an increase in CD4 + lymphocyte counts (from 483.9-×10 6 cells/ μl to 600.8 × 10 6 cells/μl), and an increase in the percentage of patients with undetectable HIV viral load (from 93.5% to 100%.)…”

Section: Pharmacogeneticsmentioning

confidence: 99%

“…The authors also report that decreasing dosage in those patients also correlated with a decrease in the percentage of patients reporting CNS adverse events (from 89.3% to 9.7%), an increase in CD4 + lymphocyte counts (from 483.9-×10 6 cells/ μl to 600.8 × 10 6 cells/μl), and an increase in the percentage of patients with undetectable HIV viral load (from 93.5% to 100%.) Interestingly, all of the patients with the 516 T/T genotype required a further reduction to 200 mg/day EFV, supporting reduction in EFV dose for slow-metabolizers [47]. An important caveat before considering dose adjustment based on pharmacogenetic testing is that EFV and other anti-retrovirals are prescribed as part of a more complex regimen (ART and HAART) and may be administered as part of a fixed-dose co-formulation.…”

Section: Pharmacogeneticsmentioning

confidence: 99%

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McDonagh¹,

Lau

Alvarellos³

et al. 2015

Pharmacogenetics and Genomics

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“…Efavirenz doses were substantially reduced down to 200 mg/d in these patients without loss of antiviral efficacy and improvement in CNS symptoms. In addition, CYP2B6 516G > T genotyping has been found to reduce treatment costs, even considering only the sparing related to efavirenz dose reduction [49] . These two reports constitute examples of practical applications of genotyping and how pharmacogenomics may be useful for the management of HIV-infected individuals receiving antiretroviral drugs.…”

Section: Nervous System Side Effectsmentioning

confidence: 99%

Can antiretroviral therapy be tailored to each human immunodeficiency virus-infected individual? Role of pharmacogenomics

Asensi¹

2015

WJV

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Pharmacogenetics refers to the effect of single nucle otide polymorphisms (SNPs) within human genes on drug therapy outcome. Its study might help clinicians to increase the efficacy of antiretroviral drugs by improving their pharmacokinetics and pharmacodynamics and by decreasing their side effects. HLAB*5701 genotyping to avoid the abacavir-associated hypersensitivity reaction (HSR) is a cost-effective diagnostic tool, with a 100% of negative predictive value, and, therefore, it has been included in the guidelines for treatment of human immunodeficiency virus (HIV) infection. HALDRB*0101 associates with nevirapine-induced HSR. CYP2B6 SNPs modify efavirenz plasma levels and their genotyping help decreasing its central nervous system, hepatic and HSR toxicities. Cytokines SNPs might influence the development of drug-associated lipodystrophy. APOA5 , APOB , APOC3 and APOE SNPs modify lipids plasma levels and might influence the coronary artery disease risk of HIV-infected individuals receiving antiretroviral therapy. UGT1A1*28 and ABCB1 (MDR1) 3435C > T SNPs modify atazanavir plasma levels and enhance hyperbilirubinemia. Much more effort needs to be still devoted to complete large prospective studies with multiple SNPs genotyping in order to reveal more clues about the role played by host genetics in antiretroviral drug efficacy and toxicity. genotyping to prevent the abacavir-associated hypersensitivity reaction. Diverse other single nucleotide polymorphisms have been described as related to certain pharmacokinetic characteristics and adverse effects of antiretroviral drugs. In this Editorial we summarize the current knowledge on this rapidly evolving field.Asensi V, Collazos J, Valle-Garay E. Can antiretroviral therapy be tailored to each human immunodeficiency virus-infected individual?

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Dose Reduction of Efavirenz: An Observational Study Describing Cost–Effectiveness, Pharmacokinetics and Pharmacogenetics

Abstract: The individualization of EFV dosage guided by genotyping 516G>T CYP2B6 and therapeutic drug monitoring could increase the efficiency of EFV use in antiretroviral treatment.

Cited by 28 publications

References 37 publications

Cost–Effectiveness of CYP2B6 Genotyping to Optimize Efavirenz Dosing in HIV Clinical Practice

Cost–Effectiveness of CYP2B6 Genotyping to Optimize Efavirenz Dosing in HIV Clinical Practice

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Can antiretroviral therapy be tailored to each human immunodeficiency virus-infected individual? Role of pharmacogenomics

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