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Race/Ethnicity and the Pharmacogenetics of Reported Suicidality With Efavirenz Among Clinical Trials Participants

BACKGROUND: We examined associations between suicidality and genotypes that predict plasma efavirenz exposure among AIDS Clinical Trials Group study participants in the United States. METHODS: Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens; suici...

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Autores principales: Mollan, Katie R, Tierney, Camlin, Hellwege, Jacklyn N, Eron, Joseph J, Hudgens, Michael G, Gulick, Roy M, Haubrich, Richard, Sax, Paul E, Campbell, Thomas B, Daar, Eric S, Robertson, Kevin R, Ventura, Diana, Ma, Qing, Edwards, Digna R. Velez, Haas, David W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853681/
https://www.ncbi.nlm.nih.gov/pubmed/28931220
http://dx.doi.org/10.1093/infdis/jix248
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author Mollan, Katie R
Tierney, Camlin
Hellwege, Jacklyn N
Eron, Joseph J
Hudgens, Michael G
Gulick, Roy M
Haubrich, Richard
Sax, Paul E
Campbell, Thomas B
Daar, Eric S
Robertson, Kevin R
Ventura, Diana
Ma, Qing
Edwards, Digna R. Velez
Haas, David W
author_facet Mollan, Katie R
Tierney, Camlin
Hellwege, Jacklyn N
Eron, Joseph J
Hudgens, Michael G
Gulick, Roy M
Haubrich, Richard
Sax, Paul E
Campbell, Thomas B
Daar, Eric S
Robertson, Kevin R
Ventura, Diana
Ma, Qing
Edwards, Digna R. Velez
Haas, David W
author_sort Mollan, Katie R
collection PubMed
description BACKGROUND: We examined associations between suicidality and genotypes that predict plasma efavirenz exposure among AIDS Clinical Trials Group study participants in the United States. METHODS: Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens; suicidality was defined as reported suicidal ideation or attempted or completed suicide. Genotypes that predict plasma efavirenz exposure were defined by CYP2B6 and CYP2A6 polymorphisms. Associations were evaluated with weighted Cox proportional hazards models stratified by race/ethnicity. Additional analyses adjusted for genetic ancestry and selected covariates. RESULTS: Among 1833 participants, suicidality was documented in 41 in exposed analyses, and 34 in on-treatment analyses. In unadjusted analyses based on 12 genotype levels, suicidality increased per level in exposed (hazard ratio, 1.11; 95% confidence interval, .96–1.27) and on-treatment 1.16; 1.01–1.34) analyses. In the on-treatment analysis, the association was strongest among white but nearly null among black participants. Considering 3 metabolizer levels (extensive, intermediate and slow), slow metabolizers were at increased risk. Results were similar after baseline covariate-adjustment for genetic ancestry, sex, age, weight, injection drug use history, and psychiatric history or recent psychoactive medication. CONCLUSIONS: Genotypes that predict higher plasma efavirenz exposure were associated with increased risk of suicidality. Strength of association varied by race/ethnicity.
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spelling pubmed-58536812018-03-23 Race/Ethnicity and the Pharmacogenetics of Reported Suicidality With Efavirenz Among Clinical Trials Participants Mollan, Katie R Tierney, Camlin Hellwege, Jacklyn N Eron, Joseph J Hudgens, Michael G Gulick, Roy M Haubrich, Richard Sax, Paul E Campbell, Thomas B Daar, Eric S Robertson, Kevin R Ventura, Diana Ma, Qing Edwards, Digna R. Velez Haas, David W J Infect Dis Major Articles and Brief Reports BACKGROUND: We examined associations between suicidality and genotypes that predict plasma efavirenz exposure among AIDS Clinical Trials Group study participants in the United States. METHODS: Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens; suicidality was defined as reported suicidal ideation or attempted or completed suicide. Genotypes that predict plasma efavirenz exposure were defined by CYP2B6 and CYP2A6 polymorphisms. Associations were evaluated with weighted Cox proportional hazards models stratified by race/ethnicity. Additional analyses adjusted for genetic ancestry and selected covariates. RESULTS: Among 1833 participants, suicidality was documented in 41 in exposed analyses, and 34 in on-treatment analyses. In unadjusted analyses based on 12 genotype levels, suicidality increased per level in exposed (hazard ratio, 1.11; 95% confidence interval, .96–1.27) and on-treatment 1.16; 1.01–1.34) analyses. In the on-treatment analysis, the association was strongest among white but nearly null among black participants. Considering 3 metabolizer levels (extensive, intermediate and slow), slow metabolizers were at increased risk. Results were similar after baseline covariate-adjustment for genetic ancestry, sex, age, weight, injection drug use history, and psychiatric history or recent psychoactive medication. CONCLUSIONS: Genotypes that predict higher plasma efavirenz exposure were associated with increased risk of suicidality. Strength of association varied by race/ethnicity. Oxford University Press 2017-09-01 2017-07-06 /pmc/articles/PMC5853681/ /pubmed/28931220 http://dx.doi.org/10.1093/infdis/jix248 Text en © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Major Articles and Brief Reports
Mollan, Katie R
Tierney, Camlin
Hellwege, Jacklyn N
Eron, Joseph J
Hudgens, Michael G
Gulick, Roy M
Haubrich, Richard
Sax, Paul E
Campbell, Thomas B
Daar, Eric S
Robertson, Kevin R
Ventura, Diana
Ma, Qing
Edwards, Digna R. Velez
Haas, David W
Race/Ethnicity and the Pharmacogenetics of Reported Suicidality With Efavirenz Among Clinical Trials Participants
title Race/Ethnicity and the Pharmacogenetics of Reported Suicidality With Efavirenz Among Clinical Trials Participants
title_full Race/Ethnicity and the Pharmacogenetics of Reported Suicidality With Efavirenz Among Clinical Trials Participants
title_fullStr Race/Ethnicity and the Pharmacogenetics of Reported Suicidality With Efavirenz Among Clinical Trials Participants
title_full_unstemmed Race/Ethnicity and the Pharmacogenetics of Reported Suicidality With Efavirenz Among Clinical Trials Participants
title_short Race/Ethnicity and the Pharmacogenetics of Reported Suicidality With Efavirenz Among Clinical Trials Participants
title_sort race/ethnicity and the pharmacogenetics of reported suicidality with efavirenz among clinical trials participants
topic Major Articles and Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853681/
https://www.ncbi.nlm.nih.gov/pubmed/28931220
http://dx.doi.org/10.1093/infdis/jix248
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