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Impact of Efavirenz Metabolism on Loss to Care in Older HIV+ Africans
Journal article   Open access   Peer reviewed

Impact of Efavirenz Metabolism on Loss to Care in Older HIV+ Africans

Jessie Torgersen, Scarlett L Bellamy, Bakgaki Ratshaa, Xiaoyan Han, Mosepele Mosepele, Athena F Zuppa, Marijana Vujkovic, Andrew P Steenhoff, Gregory P Bisson and Robert Gross
European journal of drug metabolism and pharmacokinetics, v 44(2), pp 179-187
Apr 2019
DOI: https://doi.org/10.1007/s13318-018-0507-5
PMID: 30168000
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc6420397View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Adult Age Factors Alkynes Anti-HIV Agents - metabolism Anti-HIV Agents - therapeutic use Benzoxazines - metabolism Benzoxazines - therapeutic use Blacks - genetics Botswana - epidemiology Cohort Studies Cyclopropanes Cytochrome P-450 CYP2B6 - genetics Female HIV Infections - drug therapy HIV Infections - genetics HIV Infections - metabolism Humans Male Middle Aged Prospective Studies Reverse Transcriptase Inhibitors - metabolism Reverse Transcriptase Inhibitors - therapeutic use Treatment Outcome Young Adult
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. 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. 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. 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.

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7 citations in Web of Science
8 citations in Scopus

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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Pharmacology & Pharmacy
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