Efavirenz as part of initial HIV therapy associated with increased suicidality

Initial HIV therapy that contained the antiretroviral efavirenz was associated with increased risk for suicidal ideation, attempted suicide, and completed suicide in a recent study.

Researchers analyzed participant-level data from 4 AIDS Clinical Trial Group studies conducted from 2001 to 2010 in antiretroviral-naïve patients. In each of these studies, patients were randomly assigned to a regimen that contained efavirenz or to one that did not as initial treatment for HIV. The objective of the current study was to compare time to suicidality with each type of therapy. The researchers defined suicidality as suicidal ideation or attempted or completed suicide. The study results were published in the July 1 Annals of Internal Medicine.

A total of 3,241 patients were assigned to an efavirenz-containing regimen, and 2,091 patients were assigned to a regimen that was efavirenz-free. Seventy-four percent of participants were enrolled in trials in the U.S. Seventy-three percent were men, and the median age was 37 years. Thirty-two percent of participants had a documented psychiatric history or had received psychoactive medication in the 30 days before study entry. The median follow-up was 96 weeks.

Incidence of suicidality per 1,000 person-years was 8.08 in the efavirenz group and 3.66 in the efavirenz-free group, respectively (47 vs. 15 events; hazard ratio, 2.28; P=0.006), while incidence of attempted or completed suicide per 1,000 person-years was 2.90 and 1.22, respectively (17 vs. 5 events; hazard ratio, 2.58; P=0.065). Eight patients in the efavirenz group and 1 patient in the efavirenz-free group committed suicide.

The authors noted that 3 of the 4 included trials were open-label and that no standardized questionnaire about suicidality or depression was used, among other limitations. However, they concluded that treatment-naïve patients receiving an efavirenz-containing regimen for HIV infection appeared to be at significantly increased risk for suicidality compared with patients who did not receiving a regimen containing efavirenz.

“Given the widespread use of efavirenz and severity of these adverse events, the observed increased risk is clinically relevant,” the authors wrote. Patients receiving antiretroviral therapy that includes efavirenz should undergo careful monitoring for increasing depression or evidence of suicidal behavior and thoughts, they said.