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 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 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.

The Use of Efavirenz During Pregnancy is Associated with Suicidal Ideation in Postpartum Women in Rural South Africa

“…Finally, this study reports associations that do not imply causality. Despite these limitations, a strength of the present study compared to previous studies was the assessment of efavirenz by DBS (39). …”

“…A recent study (10) has suggested that the impact of efavirenz on suicidal ideation is neither clinically relevant nor time limited, finding “no strong evidence” that self-reported initiation of efavirenz-containing ARV regimens increased suicidal thoughts. However, using DBS drug levels, the current study found that detectable efavirenz at 32-weeks predicted suicidal ideation at 12-months post-partum (36).…”

“…Previous analyses of randomized controlled trials with ARV naïve patients found that the adjusted risk of attempted or completed suicide was higher in participants receiving efavirenz, although results were not confirmed (6–9). In contrast, investigators recently found “no strong evidence” that initiation of efavirenz-containing ARV regimens increased the risk of suicidal thoughts among US patients in routine care with detectable viral load (10). However, in switch studies in which efavirenz has been changed for newer agents, discontinuation has been associated with improved neuropsychological status, and recent reports confirm the relationship between the use of efavirenz and suicidal behaviors (11), supporting the association of adverse neuropsychiatric effects with efavirenz (12).…”

Neuropsychiatric Complications of Efavirenz in Children With HIV Infection

“…Other psychiatric reactions such as hallucinations, depression and suicidal ideation were not reported by our children, but are recognized more in adults and adolescents. 24,25 Long-term manifestations included poor working memory, attention span, verbal comprehension, perceptual reasoning, processing speed and visuospatial skills, as well as poor executive functioning and borderline to extremely low IQ (ranging from 48 to 70), all of which can lead to poor academic performance. Poor neurocognitive outcomes following long-term efavirenz use, particularly decreased verbal fluency, working memory and processing speed, are reported in adults.…”

“…This caution is not only useful in South Africa, but also in other parts of sub-Saharan Africa where the CYP2B6 G>T polymorphism is widely expressed [25][26][27][28][29]. As in South Africa, routine drug monitoring and genetic testing are not available in these countries.…”