Format

Send to

Choose Destination
J Infect Dis. 2017 Sep 1;216(5):554-564. doi: 10.1093/infdis/jix248.

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

Author information

1
Center for AIDS Research.
2
Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health.
3
Division of Epidemiology, Department of Medicine.
4
Medicine, University of North Carolina at Chapel Hill.
5
Weill Cornell Medicine, Department of Medicine, New York.
6
Gilead Sciences, Foster City.
7
Division of Infectious Diseases and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
8
Department of Medicine, University of Colorado, Denver.
9
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, David Geffen School of Medicine at UCLA, California.
10
Neurology.
11
University at Buffalo, Department of Pharmacy Practice, New York.
12
Department of Obstetrics and Gynecology, Vanderbilt Genetics Institute, Vanderbilt University Medical Center.
13
Department of Medicine, Vanderbilt University School of Medicine.
14
Department of Internal Medicine, Meharry Medical College, Nashville, Tennessee.

Abstract

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.

KEYWORDS:

CYP2B6; HIV; efavirenz; pharmacogenetics; suicidality

PMID:
28931220
PMCID:
PMC5853681
DOI:
10.1093/infdis/jix248
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center