The Pharmacogenetics of HIV Treatment: A Practical Clinical Approach

Barc, Elena Álvarez

doi:10.4172/2153-0645.1000116

Cited by 3 publications

(2 citation statements)

References 103 publications

(121 reference statements)

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“…Highly polymorphic CYP2B6 is a major enzyme involved in the phase I biotransformation of some ART including nevirapine (NVP) (7). While the reasons for the ADR of nevirapine are still unclear, increasing evidence suggests that genetic factors have a role in the initiation of the toxic responses (8).…”

Section: Introductionmentioning

confidence: 99%

Cyp2b6 and Sult1a1 Single Nucleotide Polymorphism: Implication for Nevirapine-based Hiv Therapy Among Ghanaians

Prah

Asiedu-Gyekye

Nartey

et al. 2023

Preprint

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Background Nevirapine is used in many developing countries for the management of HIV-1 patients. Despite its usefulness, hypersensitivity reaction is a common complication that accounts for patients defaulting during therapy in Ghana. Genetic variations in drug-metabolizing enzymes have been implicated in reported adverse drug reactions observed in patients on nevirapine regimen. The study determined genotypic frequencies of specific CYP2B6 and SULT1A1 variants and their association with nevirapine hypersensitivity among persons living with HIV in the Ghanaian population.Methods An unmatched case-control study was conducted in a tertiary health facility in Ghana. Baseline clinical data were recorded from the patients’ folder. Genomic DNA (gDNA) samples were genotyped for CYP2B6*18 (c.983T > C) and SULT1A1*2 (c.638G > A) using Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP).Results Mean age of the patients was 38 ± 9.47 years with the majority 77.1% (54/70) of the participants being females. For CYP2B6*18 (c.983T > C) genotype frequencies, T/T and T/C were 94.3% (66/70) and 5.7% (4/70) respectively while for SULT1A1*2 (c.638G > A) genotype frequencies, G/G, G/A, and A/A were 61.4% (43/70), 34.3% (24/70) and 4.3% (3/70) respectively. The prevalence of CYP2B6*18 (c.983T > C) and SULT1A1*2 (c.638G > A) minor allele were 2.9% (4/140) and 21.4% (30/140) respectively among the study participants.Conclusion Extensive metabolizer genotypes for CYP2B6*18 (c.983T > C) and SULT1A1*2 (c.638G > A) were more common than the intermediate and poor metabolizer genotype. However, CYP2B6 983C/C representing poor metabolizers of CYP2B6*18 (c.983T > C) were not detected among the study population. Genetic polymorphism of CYP2B6*18 (c.983T > C) and SULT1A1*2 (c.638G > A) were not associated with nevirapine hypersensitivity. However, these variants may contribute to differential variations of other drug responses among the Ghanaian population.

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Section: Introductionmentioning

confidence: 99%

Cyp2b6 and Sult1a1 Single Nucleotide Polymorphism: Implication for Nevirapine-based Hiv Therapy Among Ghanaians

Prah

Asiedu-Gyekye

Nartey

et al. 2023

Preprint

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“…The benefit of pharmacogenetic testing is to guide the choice of the initial drug regimen, thus increasing efficacy, and simultaneously avoiding ADRs 6. Genetic variations can impact the pathways of drug absorption, disposition, metabolism and excretion (ADME) 7. A mutation in a gene coding for a drug-metabolizing enzyme can result in an enzyme with normal, low, or no activity 8.…”

Section: Introductionmentioning

confidence: 99%

<p>Adverse Drug Reactions Associated with CYP 2B6 Polymorphisms in HIV/AIDS-Treated Patients in Yaoundé, Cameroon</p>

Nkenfou

Tiedeu

Nkenfou

et al. 2019

TACG

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PurposeThe metabolism of antiretroviral drugs is subject to individual variations of the CYP 2B6 gene. The objective of this study was to evaluate the prevalence of CYP 2B6 516 G>T and 983 T>C polymorphisms and investigate their association with the development of adverse drug reactions (ADRs) in people living with HIV/AIDS in Cameroon.Patients and methodsA total number of 122 patients, attending the Yaoundé Central Hospital HIV Day Clinic, consented to take part in this study. Blood specimens were collected and DNA was extracted using the Chelex method. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was performed for the detection of CYP 2B6 Single-Nucleotide Polymorphisms (SNPs). Genotype frequencies were compared between groups with or without ADRs. Logistic regression analysis was performed to assess association between genotype and adverse effects of antiretroviral therapy (ART).ResultsThree types of metabolizers were identified: extensive, intermediate and slow. For the 516G>T polymorphism, prevalences of 8.2% GG, 65.6% GT and 26.2% TT were obtained. For the 983T>C polymorphism, 89.3% TT, 4.1% CT and 6.6% CC prevalences were obtained. Those homozygous for the wild-type allele (516GG) were less likely to develop ADR with a statistically significant difference (OR=0.885, P=0.029). For the CYP2B6 T983C SNP, homozygous mutants (CC) may present a higher risk (threefold) of developing adverse reactions (OR=2.677, P=0.164).ConclusionThese findings demonstrate that ADRs among HIV/AIDS patients under ART may be associated with the genetic variability of the metabolizing enzyme CYP 2B6. Genotyping for this gene may guide the better administration of Efavirenz and Nevirapine to Cameroonian patients.

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Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals

Nwogu

Babalola

et al. 2016

AIDS Research and Treatment

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Neurological complications associated with the human immunodeficiency virus (HIV) are a matter of great concern. While antiretroviral (ARV) drugs are the cornerstone of HIV treatment and typically produce neurological benefit, some ARV drugs have limited CNS penetration while others have been associated with neurotoxicity. CNS penetration is a function of several factors including sieving role of blood-brain and blood-CSF barriers and activity of innate drug transporters. Other factors are related to pharmacokinetics and pharmacogenetics of the specific ARV agent or mediated by drug interactions, local inflammation, and blood flow. In this review, we provide an overview of the various factors influencing CNS penetration of ARV drugs with an emphasis on those commonly used in sub-Saharan Africa. We also summarize some key associations between ARV drug penetration, CNS efficacy, and neurotoxicity.

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The Pharmacogenetics of HIV Treatment: A Practical Clinical Approach

Cited by 3 publications

References 103 publications

Cyp2b6 and Sult1a1 Single Nucleotide Polymorphism: Implication for Nevirapine-based Hiv Therapy Among Ghanaians

Cyp2b6 and Sult1a1 Single Nucleotide Polymorphism: Implication for Nevirapine-based Hiv Therapy Among Ghanaians

<p>Adverse Drug Reactions Associated with CYP 2B6 Polymorphisms in HIV/AIDS-Treated Patients in Yaoundé, Cameroon</p>

Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals

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