Evidence regarding potential adverse neuropsychiatric effects of efavirenz is conflicting, and data from sub-Saharan Africa, where 70% of persons living with HIV (PLHIV) reside and efavirenz is used as first-line therapy, are limited.
To estimate associations between efavirenz use and depression and suicidal ideation among PLHIV in Uganda.
Prospective observational cohort study. (ClinicalTrials.gov: NCT01596322)
Adult PLHIV enrolled at the start of antiretroviral therapy (ART) and observed every 3 to 4 months from 2005 to 2015.
The exposure of interest was time-varying efavirenz use, defined as use during the 7 days and in 60 or more of the 90 days before a study visit, compared with nevirapine use. Self-reported outcomes were depression, defined as a mean score greater than 1.75 on the Hopkins Symptom Checklist depression subscale, and suicidal ideation. Multivariable-adjusted generalized estimating equations (GEE) logistic regression, Cox proportional hazards regression, and marginal structural models were fit to estimate the association between efavirenz use and the risk for depression and suicidal ideation.
694 participants (median age, 33 years; median pretreatment CD4+ count, 1.8 × 109 cells/L) contributed 1200 person-years of observation (460 person-years receiving efavirenz). No baseline differences in depression or suicidal ideation were found between patients ever exposed to efavirenz and those never exposed to efavirenz and receiving nevirapine (P > 0.80 for both). Of 305 participants ever-exposed to efavirenz, 61 (20.0%) and 19 (6.2%) had depression and suicidal ideation, respectively, on at least 1 follow-up visit, compared with 125 (32.1%) and 47 (12.1%) of the 389 who received nevirapine. In adjusted GEE models, efavirenz use was associated with decreased odds of depression compared with nevirapine use (adjusted odds ratio, 0.62 [95% CI, 0.40 to 0.96]) and was not significantly associated with suicidal ideation (adjusted odds ratio, 0.61 [CI, 0.30 to 1.25]). Time-to-event and marginal structural models yielded similar estimates.
Nonrandom assignment to treatment and substantial differences between the efavirenz and nevirapine groups.
No evidence was found that use of efavirenz in first-line ART increased the risk for depression or suicidal ideation compared with nevirapine use among PLHIV in Uganda.
Primary Funding Source:
National Institutes of Health.
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Author, Article, and Disclosure Information
Jonathan L. Chang,
Duke University School of Medicine, Durham, North Carolina, and Massachusetts General Hospital, Boston, Massachusetts (J.L.C.)
Mbarara University of Science and Technology, Mbarara, Uganda (A.C.T., N.M., C.M., M.B.)
Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (J.E.H.)
Mbarara University of Science and Technology, Mbarara, Uganda; Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Epicentre Mbarara, Mbarara, Uganda (Y.B.)
University of California, San Francisco, San Francisco, California (J.N.M., P.W.H.)
Mbarara University of Science and Technology, Mbarara, Uganda, and Oregon Health & Science University, Portland, Oregon (D.R.B.)
Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, and Mbarara University of Science and Technology, Mbarara, Uganda (M.J.S.)
Grant Support: By the NIH (grants R01 MH054907, U01 CA066529, and K23 MH099916), University of California, San Francisco, Gladstone Center for AIDS Research (grant P30AI027763), Harvard Center for AIDS Research (grant P30AI060354), and Doris Duke Charitable Foundation.
Disclosures: Dr. Haberer reports grants from NIH during the conduct of the study and personal fees from Merck outside the submitted work. Dr. Martin reports grants from NIH during the conduct of the study. Dr. Hunt reports grants from NIH during the conduct of the study and personal fees from Merck, Gilead, and ViiV outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-2252.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Corresponding Author: Jonathan L. Chang, MPH, 16 St Elias Drive, Durham, NC 27705; e-mail, jonathan.
Current Author Addresses: Mr. Chang: 16 St Elias Drive, Durham, NC 27705.
Dr. Tsai: 9 Bow Street, Cambridge, MA 02138.
Mr. Musinguzi and Drs. Muzoora and Bwana: Mbarara University of Science and Technology, P.O. Box 1410, Mbarara, Uganda.
Dr. Haberer: Massachusetts General Hospital Global Health, 100 Cambridge Street, 15th Floor, Boston, MA 02114.
Dr. Boum: Epicentre Mbarara Research Center, P.O. Box 1856, Mbarara, Uganda.
Dr. Martin: 550 16th Street, San Francisco, CA 94158.
Dr. Hunt: 1001 Potrero Avenue, San Francisco, CA 94110.
Dr. Bangsberg: Office of the Dean, MC: GH230, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239.
Dr. Siedner: 55 Fruit Street, Boston, MA 02114.
Author Contributions: Conception and design: J.L. Chang, A.C. Tsai, M.J. Siedner.
Analysis and interpretation of the data: J.L. Chang, A.C. Tsai, J.E. Haberer, C. Muzoora, J.N. Martin, P.W. Hunt, M.J. Siedner.
Drafting of the article: J.L. Chang, J.E. Haberer, Y. Boum, C. Muzoora, J.N. Martin, P.W. Hunt.
Critical revision for important intellectual content: J.L. Chang, A.C. Tsai, Y. Boum, C. Muzoora, J.N. Martin, P.W. Hunt, D.R. Bangsberg, M.J. Siedner.
Final approval of the article: J.L. Chang, A.C. Tsai, N. Musinguzi, J.E. Haberer, Y. Boum, C. Muzoora, M. Bwana, J.N. Martin, P.W. Hunt, D.R. Bangsberg, M.J. Siedner.
Provision of study materials or patients: C. Muzoora, M. Bwana, J.N. Martin.
Statistical expertise: A.C. Tsai, M.J. Siedner.
Obtaining of funding: J.N. Martin, P.W. Hunt, D.R. Bangsberg.
Administrative, technical, or logistic support: C. Muzoora, J.N. Martin.
Collection and assembly of data: N. Musinguzi, J. Haberer, Y. Boum, C. Muzoora, M. Bwana, J.N. Martin, P.W. Hunt, D.R. Bangsberg.
This article was published at Annals.org on 26 June 2018.