Depression and suicidal ideation among HIV-infected adults receiving efavirenz versus nevirapine in Uganda: a prospective cohort study

Abstract

Background: There is conflicting evidence about potential adverse neuropsychiatric effects of efavirenz and limited data from sub-Saharan Africa, where efavirenz is used as first-line therapy and 70% of people living with HIV (PLHIV) reside. Objective: To estimate associations between efavirenz use, depression, and suicidal ideation among PLHIV in Uganda. Design: Prospective observational cohort study Setting: Mbarara, Uganda Participants: Adult PLHIV enrolled at antiretroviral therapy (ART) initiation and observed every 3–4 months during 2005–2015 Measurements: Our exposure of interest was time-varying efavirenz use, defined by use in the 7 days and 60 or more of the 90 days prior to a study visit, as compared to nevirapine use. Self-reported outcomes were: (1) depression, defined by a mean score >1.75 on the Hopkins Symptom Checklist depression subscale; and (2) suicidal ideation. We fit multivariable-adjusted generalized estimating equations (GEE) logistic regression models, Cox proportional hazard regression models, and marginal structural models (MSM) to estimate the association between efavirenz and risk of depression and suicidal ideation. Results: 694 participants (median age 33, median pre-treatment CD4+ count 180 cells/μL) contributed 1,200 person-years of observation (460 person-years on efavirenz). There were no baseline differences in depression or suicidal ideation between those ever-exposed to efavirenz and those never-exposed and receiving nevirapine (both P>0.80). 61/305 (20.0%) and 19/305 (6.2%) participants ever-exposed to efavirenz had at least one follow-up visit with depression and suicidal ideation, respectively, compared to 125/389 (32.1%) and 48/389 (12.3%) of participants receiving nevirapine. In adjusted GEE models, efavirenz use was associated with decreased odds of depression compared to nevirapine use (adjusted odds ratio [AOR], 0.62 [95% CI, 0.40 to 0.96]) and was not significantly associated with suicidal ideation (AOR, 0.61 [95% CI, 0.30 to 1.26]). Time-to-event and MSM models yielded similar estimates. Limitations: Non-random assignment to treatment with substantial differences between participants receiving efavirenz or nevirapine Conclusions: We found no evidence that use of efavirenz in first-line ART increased risk of depression or suicidal ideation compared with nevirapine among PLHIV in Uganda.