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Accepted (AM)Open Access (License Unspecified), Open
Journal article
CYP2B6 genotypes and early efavirenz-based HIV treatment outcomes in Botswana
AIDS (London), v 31(15), pp 2107-2113
24 Sep 2017
PMID: 28692529
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Objectives: To determine the association between cytochrome p450 2B6 genotypes and efavirenz-based HIV treatment outcomes.
Design: Observational cohort study of HIV-infected adults initiating efavirenz-based regimens in Botswana.
Methods: The primary endpoint was a composite of death or loss to care or HIV RNA more than 25 copies/ml at 6 months. CYP2B6 516G>T and 983T>C genotyping was done with Taqman Open Array platform. Adverse experiences were measured by using the Subject Experience Questionnaire. Metabolism alleles were included in logistic regression models of the composite endpoint.
Results: A total of 801 individuals included 406 (51%) men, median age 37 years, median baseline CD4(+) cell count 195 cells/ml, and plasma HIV RNA 4.9 log(10) copies/ml. 288 (36%) reached the endpoint, including 34 (4%) deaths, 151 (19%) lost to care, 11 (1%) lost to the study, but alive and in care, and 92 (11%) with plasma HIV RNA more than 25 copies/ml. Metabolism variant alleles were common with 396 (49%) intermediate and 192 (24%) slow metabolizers. There were no statistically significant associations between metabolism and treatment endpoints. However, slower metabolism was associated with fewer adverse experiences.
Conclusion: Slow metabolism alleles were associated with lower efavirenz clearance but not any of the treatment endpoints. Slow efavirenz metabolism did not exacerbate central nervous system toxicity. These results should allay concern that slow efavirenz metabolism adversely impacts individuals in sub-Saharan African settings in which these alleles are common. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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Details
- Title
- CYP2B6 genotypes and early efavirenz-based HIV treatment outcomes in Botswana
- Creators
- Robert Gross - Rutgers Biomedical and Health SciencesScarlett L. Bellamy - Drexel Univ, Dornsife Sch Publ Hlth, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USABakgaki Ratshaa - Botswana UPenn Partnership, Gaborone, BotswanaXiaoyan Han - Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, 804 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USAMarijana Vujkovic - Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USARichard Aplenc - Univ Penn, Perelman Sch Med, Dept Epidemiol, Philadelphia, PA 19104 USAAndrew P. Steenhoff - Botswana UPenn Partnership, Gaborone, BotswanaMosepele Mosepele - Univ Botswana, Fac Med, Gaborone, BotswanaGanesh Moorthy - Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USAAthena F. Zuppa - Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USABrian L. Strom - Rutgers Univ New Brunswick, Rutgers Biomed & Hlth Sci, Off Chancellor, New Brunswick, NJ USAGregory P. Bisson - Univ Penn, Perelman Sch Med, Dept Med Infect Dis, Philadelphia, PA 19104 USA
- Publication Details
- AIDS (London), v 31(15), pp 2107-2113
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 7
- Grant note
- D43TW009781 / FOGARTY INTERNATIONAL CENTER; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Fogarty International Center (FIC) Ministry of Health of Botswana R01 MH080701 / U.S. National Institute of Mental Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) P30 AI045008 / National Institute of Allergy and Infectious Diseases (Penn Center for AIDS Research) P30MH097488 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) P30 MH097488 / U.S. National Institute of Mental Health (Penn Mental Health AIDS Research Center) P30AI045008 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Epidemiology and Biostatistics
- Web of Science ID
- WOS:000410727600008
- Scopus ID
- 2-s2.0-85022196342
- Other Identifier
- 991019167845704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology
- Infectious Diseases
- Virology