Prediction of plasma efavirenz concentrations among HIV-positive patients taking efavirenz-containing combination antiretroviral therapy

Tiedeu

et al. 2019

TACG

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.

Section: Discussionsupporting

confidence: 88%

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

Tiedeu

et al. 2019

TACG

“…Previous studies reported that patients experiencing severe AEs were more likely to have a lower BMI [8,30]. One such study in Ghana found that patients with BMI < 16 kg/m 2 had increased risk of neuropsychiatric toxicity (aHR: 1.44; 95% CI: 1.02-2.03) [31], perhaps due to higher blood concentration of EFV, which is expected in underweight people [32]. However, we found that the risk of AE may increase with increased BMI.…”

Section: Discussionmentioning

confidence: 99%

Adverse events in Chinese human immunodeficiency virus (HIV) patients receiving first line antiretroviral therapy

Dai

Liu

et al. 2020

BMC Infect Dis

Background: Although the global human immunodeficiency virus (HIV) epidemic has improved significantly due to antiretroviral treatment (ART), ART-related adverse events (AEs) remain an issue. Therefore, investigating the factors associated with ART-related AEs may provide vital information for monitoring risks. Methods: A prospective cohort study was conducted among adult patients (aged 18 years or older) with HIV who received Tenofovir (TDF) + Lamivudine (3TC) + Efavirenz (EFV) as first-line ART regimens. All AEs during the first 12 months of therapy were recorded. Logistic regression analysis was used to identify variables associated with AEs. Results: Four hundred seventy-four patients receiving TDF+ 3TC+ EFV ART regimens between March 2017 and October 2017 were included in the study analysis. Among them, 472 (99.6%) experienced at least one AE, 436 (92.0%) patients experienced at least one AE within 1 month of treatment, 33 (7.0%) between one and 3 months of treatment, and three (0.6%) patients after 3 months of treatment. The most commonly reported AE was nervous system (95.6%) related, followed by dyslipidemia (79.3%), and impaired liver function (48.1%). Patients with baseline body mass index (BMI) greater than 24 kg/m 2 (adjusted OR 1.77, 95%CI 1.03-3.02), pre-existing multiple AEs (adjusted OR 2.72, 95%CI 1.59-4.64), and pre-existing severe AEs (adjusted OR 5.58, 95%CI 2.65-11.73) were at increased odds of developing a severe AE. Patients with baseline BMI greater than 24 kg/m 2 (adjusted OR 2.72, 95%CI 1.25-5.89) were more likely to develop multiple AEs. Conclusion: The incidence of ART-related adverse events over a 12-month period in China was high. Baseline BMI greater than 24 kg/m 2 , pre-existing multiple AEs, and pre-existing severe AEs were shown to be independent risk factors for developing a severe AE.

JAIDS Journal of Acquired Immune Deficiency Syndromes

“…The participants were taking daily 600-mg EFV-based cART and had EFV C12 determined after a minimum exposure of 14 days (EFV C12 were measured after a median of 473.5 days of EFV exposure and after 28 days in 95.4% of participants). 21 CYP2B6 516G>T polymorphism was also determined. Those who were on 600-mg EFV for at least 240 weeks without interruption were screened for inclusion in this study.…”

Section: Methodsmentioning

confidence: 99%

“…The methods for determination of plasma concentrations of EFV and the single-nucleotide polymorphism of CYP2B6 516G>T had been described previously. 21 Because participants were advised to take EFV at bedtime to reduce the neuropsychiatric adverse effects, measurement of peak or trough concentrations was logistically difficult. Thus, mid-dose blood samples (12 ± 2 hours after the patients' self-reported time of the last EFV dose) were collected.…”

Section: Methodsmentioning

confidence: 99%

Impact of Efavirenz Mid-dose Plasma Concentration on Long-Term Weight Change Among Virologically Suppressed People Living With HIV

Huang

Lin

et al. 2021

Self Cite

Background: Pharmacogenetic studies have shown that slow and intermediate metabolizers of efavirenz (EFV) gained less weight compared with extensive metabolizers. It is hypothesized that increased EFV exposure suppresses weight gain. We investigated the effect of EFV mid-dose plasma concentration (C12) on long-term weight change among virologically suppressed people living with HIV (PLWH).Methods: Participants in a prospective EFV pharmacokinetic study were included if they had been taking EFV-containing combination antiretroviral therapy for more than 240 weeks and had 3 or more weight measurements. The weight changes and time to $5% of weight gain over 192 weeks were compared between PLWH with higher and those with lower EFV C12 (using mean population C12 as the cutoff). EFV C12 and CYP2B6 516G.T polymorphism were examined in generalized estimating equations and in a Cox proportional hazards model for associations with weight gain, after adjustments for age, sex, companion antiretroviral agent, CD4 lymphocyte count, and plasma HIV RNA.Results: One hundred eighteen PLWH were included. PLWH with higher EFV C12 had less mean weight gain compared with those with lower C12 after 192 weeks (20.09 vs +1.58 kg, P = 0.033). PLWH with higher C12 were less likely to gain $5% weight in Kaplan-Meier analysis (P = 0.0003). In both generalized estimating equations and Cox proportional hazards models, a higher EFV C12 was associated with less weight gain, while CYP2B6 516G.T was not, after adjustments made for confounding factors.Conclusions: Our findings support that increased EFV exposure was associated with less weight gain.