The relationship between efavirenz as initial antiretroviral therapy and suicidal thoughts among HIV-infected adults in routine care

BACKGROUND:Evidence about the effect of initiating efavirenz-containing combination antiretroviral therapy (ART) as 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 followingfirst suicidal thoughts, discontinuation of initial ART regimen, death, loss to care (>12 months with no HIV appointments), or administrative censoring (2014 to 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% CI 0.53, 1.45), and above the null in the weighted analysis (HR 1.21, 95% CI 0.66, 2.28). Among those with a prior mental health issue, the weighted HR was 1.76 (95% CI 0.45, 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.