Abstract:
:BACKGROUND AND OBJECTIVE: Efavirenz is commonly used in Africa and is frequently associated with neurocognitive toxicity, which may compromise clinical outcomes. Older individuals are at increased risk for drug toxicity and clinical outcomes may be worse in older age, particularly among those individuals with cytochrome P450 (CYP) 2B6 polymorphisms associated with slower efavirenz metabolism. The aim of this study was to determine if the CYP2B6 polymorphisms differentially impacts loss to care in older people. METHODS:We conducted a prospective cohort study of 914 treatment-naïve HIV+ adults initiating efavirenz-based antiretroviral treatment at public HIV clinics in Gaborone, Botswana between 2009 and 2013. Older age, defined as age ≥ 50 years, was the primary exposure and loss to care at 6 months was the primary outcome. Interaction between age and CYP2B6 516G>T and 983T>C polymorphisms, defined as extensive, intermediate, and slow metabolism, was assessed. Neurocognitive toxicity was measured using a symptom questionnaire. Age-stratified logistic regression was performed to identify factors associated with loss to care. RESULTS:Older age was associated with loss to care (OR 1.95, 95% CI 1.30-2.92). Age modified the effect of CYP2B6 genotype on loss to care with older, slow metabolizers at over four-fold higher risk when compared to older, intermediate metabolizers (OR 4.06 95% CI 1.38-11.89); neurocognitive toxicity did not mediate this risk. CYP2B6 metabolism genotype did not increase risk of loss to care in younger participants. CONCLUSION:Older age was associated with loss to care, especially among those with slow efavirenz metabolism. Understanding the relationship between older age and CYP2B6 genotype will be important to improving outcomes in an aging population initiating efavirenz-based ART in similar settings.
journal_name
Eur J Drug Metab Pharmacokinetjournal_title
European journal of drug metabolism and pharmacokineticsauthors
Torgersen J,Bellamy SL,Ratshaa B,Han X,Mosepele M,Zuppa AF,Vujkovic M,Steenhoff AP,Bisson GP,Gross Rdoi
10.1007/s13318-018-0507-5subject
Has Abstractpub_date
2019-04-01 00:00:00pages
179-187issue
2eissn
0378-7966issn
2107-0180pii
10.1007/s13318-018-0507-5journal_volume
44pub_type
杂志文章abstract::The binding of three digitalis glycosides, digitoxin, digoxin and gitoxin, to human serum albumin was studied in vitro by equilibrium dialysis. The results obtained showed that binding is a non saturable process and that probably the same binding mechanism is involved for each of the three drugs. Their binding sites s...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189456
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journal_title:European journal of drug metabolism and pharmacokinetics
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journal_title:European journal of drug metabolism and pharmacokinetics
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journal_title:European journal of drug metabolism and pharmacokinetics
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journal_title:European journal of drug metabolism and pharmacokinetics
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journal_title:European journal of drug metabolism and pharmacokinetics
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journal_title:European journal of drug metabolism and pharmacokinetics
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journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-016-0327-4
更新日期:2017-02-01 00:00:00
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journal_title:European journal of drug metabolism and pharmacokinetics
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journal_title:European journal of drug metabolism and pharmacokinetics
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journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189490
更新日期:1981-01-01 00:00:00
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journal_title:European journal of drug metabolism and pharmacokinetics
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doi:10.1007/BF03189562
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journal_title:European journal of drug metabolism and pharmacokinetics
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journal_title:European journal of drug metabolism and pharmacokinetics
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journal_title:European journal of drug metabolism and pharmacokinetics
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journal_title:European journal of drug metabolism and pharmacokinetics
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journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
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