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CYP2B6 variants and plasma efavirenz concentrations during antiretroviral therapy in Port-au-Prince, Haiti.

ABSTRACT: Polymorphisms in CYP2B6 are known to predict increased steady-state plasma concentrations of efavirenz. We characterized relationships between genetic polymorphisms and plasma efavirenz concentrations among 45 Haitians who initiated antiretroviral therapy in Port-au-Prince.An observational study characterized relationships between clinical factors, pharmacokinetics, and treatment response among antiretroviral-naive patients initiating once-daily treatment with efavirenz plus twice-daily treatment with zidovudine and lamivudine. Plasma drug concentrations were determined at weeks 2 and 4. Drug doses were directly observed by field workers or designated family members. We retrospectively characterized relationships between efavirenz concentrations and 50 single-nucleotide polymorphisms in CYP2B6 and several polymorphisms in CYP2A6, CYP3A4, CYP3A5, and ABCB1.Plasma specimens for efavirenz analysis were obtained from study participants a mean (+/- standard deviation) of 13.9 +/- 1.6 h after they received the dose. As expected, CYP2B6 516G-->T was associated with increased plasma efavirenz concentrations (Spearman rho = 0.71; P < .001), as were 10 polymorphisms in linkage disequilibrium with 516G-->T. Distinct CYP2B6 polymorphisms were associated with decreased plasma efavirenz concentrations (greatest absolute rho = 0.48; P = .001). Associations were replicated by results from a recent pharmacokinetic study involving 34 healthy, human immunodeficiency virus-negative African Americans.Relatively frequent CYP2B6 polymorphisms may predict decreased plasma efavirenz exposure in patients of African descent. If replicated in other cohorts, the implications of these novel associations for treatment response warrant further study.

SUBMITTER: Leger P

PROVIDER: S-EPMC2754599 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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CYP2B6 variants and plasma efavirenz concentrations during antiretroviral therapy in Port-au-Prince, Haiti.

Leger Paul P Dillingham Rebecca R Beauharnais Carole Anne CA Kashuba Angela D M AD Rezk Naser L NL Fitzgerald Daniel W DW Pape Jean William JW Haas David W DW

The Journal of infectious diseases 20090901 6

<h4>Background</h4>Polymorphisms in CYP2B6 are known to predict increased steady-state plasma concentrations of efavirenz. We characterized relationships between genetic polymorphisms and plasma efavirenz concentrations among 45 Haitians who initiated antiretroviral therapy in Port-au-Prince.<h4>Methods</h4>An observational study characterized relationships between clinical factors, pharmacokinetics, and treatment response among antiretroviral-naive patients initiating once-daily treatment with ...[more]

PMID: 19659438

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Project description:IntroductionDiabetes mellitus is a chronic noncommunicable disease associated with death and major disability, with increasing prevalence in low- and middle-income countries. There is limited population-based data about diabetes in Haiti. The objective of this study was to assess the prevalence of diabetes and associated factors among adults in Port-au-Prince, Haiti using a population-based cohort.MethodsThis study analyzes cross-sectional enrollment data from the population-based Haiti Cardiovascular Disease Cohort Study, conducted using multistage sampling with global positioning system waypoints in census blocks in the metropolitan area of Port-au-Prince, Haiti. A total of 3,005 adults ≥18 years old were enrolled from March 2019 to August 2021. We collected socio-demographic data, health-related behaviors, and clinical data using standardized questionnaires. Diabetes was defined as any of the following criteria: enrollment fasting glucose value ≥ 126 mg/dL or non-fasting glucose ≥ 200 mg/dL, patient self-report of taking diabetes medications, or study physician diagnosis of diabetes based on clinical evaluation.ResultsAmong 2985 (99.3%) with complete diabetes data, median age was 40 years, 58.1% were female, and 17.2% were obese. The prevalence of diabetes was 5.4% crude, and 5.2% age standardized. In unadjusted analysis, older age, higher body mass index (BMI), low physical activity, low education were associated with a higher odds of diabetes. After multivariable logistic regression, older age [60+ vs 18-29, Odds Ratio (OR)17.7, 95% CI 6.6 to 47.9] and higher BMI (obese vs normal/underweight, OR 2.7, 95% CI 1.7 to 4.4) remained statistically significantly associated with higher odds of diabetes.ConclusionThe prevalence of diabetes was relatively low among adults in Port-au-Prince, but much higher among certain groups (participants who were older and obese). The Haitian health system should be strengthened to prevent, diagnose, and treat diabetes among high-risk groups.

Project description:BackgroundEighty percent of global cardiovascular disease (CVD) is projected to occur in low- and middle -income countries (LMICs), yet local epidemiological data are scarce. We provide the first population-based, adjudicated CVD prevalence estimates in Port-au-Prince, Haiti to describe the spectrum of heart disease and investigate associated risk factors.MethodsDemographic, medical history, clinical, imaging and laboratory data were collected among adults recruited using multistage random sampling from 2019 to 2021. Prevalent CVD (heart failure, stroke, ischemic disease) were adjudicated using epidemiological criteria similar to international cohorts. Multivariable Poisson regressions assessed relationships between risk factors and prevalent CVD.FindingsAmong 3003 participants, median age was 40 years, 58.1% were female, 70.2% reported income <1 USD/day, and all identified as Black Haitian. CVD age-adjusted prevalence was 14.7% (95% CI 13.3%, 16.5%), including heart failure (11.9% [95% CI 10.5%, 13.5%]), stroke (2.4% [95% CI 1.9%, 3.3%]), angina (2.1% [95% CI 1.6%, 2.9%]), myocardial infarction (1.0% [95% CI 0.6%, 1.8%]), and transient ischemic attack (0.4% [95% CI 0.2%, 1.0%]). Among participants with heart failure, median age was 57 years and 68.5% of cases were among women. The most common subtype was heart failure with preserved ejection fraction (80.4%). Heart failure was associated with hypertension, obesity, chronic kidney disease, depression, and stress.InterpretationEarly-onset heart failure prevalence is alarmingly high in urban Haiti and challenge modelling assumptions that ischemic heart disease and stroke dominate CVDs in LMICs. These data underscore the importance of local population-based epidemiologic data within LMICs to expedite the selection and implementation of evidence-based cardiovascular health policies targeting each country's spectrum of heart disease.FundingThis study was funded by NIH grants R01HL143788, D43TW011972, and K24HL163393, clinicaltrials.govNCT03892265.

Dataset Information

CYP2B6 variants and plasma efavirenz concentrations during antiretroviral therapy in Port-au-Prince, Haiti.

Publications

CYP2B6 variants and plasma efavirenz concentrations during antiretroviral therapy in Port-au-Prince, Haiti.

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