The Relationship Between Efavirenz as Initial Antiretroviral Therapy and Suicidal Thoughts Among HIV-Infected Adults in Routine Care

Abstract

Background: Evidence about the effect of initiating efavirenz-containing combination antiretroviral therapy (ART) as the first-line therapy on suicidal thoughts remains conflicting.

Methods: Using data from a cohort of HIV-infected adults enrolled in routine care across 5 sites in the United States, we included participants with a baseline patient-reported outcome measure and detectable viral load who initiated ART between 2011 and 2014. Participants were followed until the earliest of the following: first suicidal thoughts, discontinuation of initial ART regimen, death, loss to care (>12 months with no HIV appointments), or administrative censoring (2014-2015). Suicidal thoughts were measured using a Patient Health Questionnaire-9 item. We used weighted marginal structural Cox models to estimate the effect of initiating efavirenz-containing ART, versus efavirenz-free ART, on the hazard of active or passive suicidal thoughts after ART initiation, accounting for confounding by channeling bias.

Results: Overall, 597 participants were followed for a median of 19 months (13,132 total person-months); 147 (25%) initiated efavirenz-containing ART. At ART initiation, 38% of participants reported suicidal thoughts or depressive symptoms. Initiating efavirenz-based ART was associated with a hazard ratio (HR) for suicidal thoughts below the null in the crude analysis [HR, 0.88; 95% confidence interval (CI): 0.53 to 1.45] and above the null in the weighted analysis (HR, 1.21; 95% CI: 0.66 to 2.28). Among those with a prior mental health issue, the weighted HR was 1.76 (95% CI: 0.45 to 6.86).

Conclusions: After accounting for measured channeling bias, we observed no strong evidence that initiating efavirenz-containing ART increased the hazard of suicidal thoughts.

Figure 1

Inclusion criteria for 597 HIV-infected adults in CNICS who initiated ART between 2011 and 2014 and had a Patient Reported Outcome (PRO) within 6 months prior or up to 1 week after initiating ART and had a detectable viral load at ART initiation.

Figure 2

A) Unadjusted and B) Weighted Kaplan-Meier curves showing the cumulative probability of suicidal ideation for individuals who initiated efavirenz-containing ART and those who initiated efavirenz-free ART in CNICS between 2011 and 2014 through 36 months (1 event occurred after 36 months). Weighted estimates are weighted by the product of inverse probability of treatment weights to account for challenging-in bias, inverse probability of censoring weights to account for potentially informative loss to follow-up, and inverse probability of observation weights to account for not having an observed patient reported outcome assessment at least once within a 6-month period.