Efavirenz for Initial Therapy of HIV Associated with Increased Suicide Risk

Different antiretroviral medications have different side effect profiles. Efavirenz is a non-nucleoside reverse transcriptase inhibitor widely used to treat HIV.¹ While typically associated with CNS side effects, serious psychiatric side effects have also been reported.²

A new study published in the Annals of Internal Medicine examined the relationship between efavirenz use and suicide, suicide attempt, or suicidal ideation.³ The investigators analyzed data from 4 AIDS Clinical Trials Groups, antiretroviral-naïve studies between 2001 and 2010. Within each study, subjects were randomly assigned to either an efavirenz-containing regimen or an efavirenz-free regimen. Most of the study participants were men (73%) and the median age was 37 years. Notably, 32% of study participants had documented psychiatric conditions or had received psychoactive medications within 30 days of entering the study.

Overall, 8 suicides occurred in the efavirenz group: only 1 in the efavirenz-free group was reported. The incidence of per 1000 person-years was significantly higher in the efavirenz group (8.08 (47 events) in the efavirenz group and 3.66 (15 events) in the efavirenz-free group (hazard ratio, 2.28 [95% CI, 1.27 to 4.10]; P = 0.006). Similarly, the incidence of attempted or completed suicide was 2.90 (17 events) and 1.22 (5 events) in the efavirenz and efavirenz-free groups, respectively (hazard ratio, 2.58 [CI, 0.94 to 7.06]; P = 0.065).

This study demonstrated a statistically significant association between efavirenz for the initial treatment of HIV and suicidal thoughts or behavior, but it had some limitations. Notably, 3 out of the 4 trials were open label and thus susceptible to reporting bias. Also, there were no standardized questionnaires for suicidality or depression.

Key Point: Physicians who treat patients with HIV infection should be aware that a statistically significant association exists between efavirenz for initial HIV therapy and the risk suicidality. When this drug is given as a component of an antiretroviral drug regimen, patients should be monitored carefully for the possibility of deterioration of their depression or evidence of suicidal behavior-especially patients with risk factors for suicide or depression.

References:

1. Thompson MA, Aberg JA, Hoy JF, et al. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel. JAMA. 2012;308:387-402.
2. Staszewski S, Morales-Ramirez J, Tashima KT, et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med. 1999; 341:1865-1873.
3. Mollan KR, Smurzynski M, Eron JJ, et al. Association between efavirenz as initial therapy for HIV-1 infection and increased risk for suicidal ideation or attempted or completed suicide: an analysis of trial data. Ann Intern Med.2014;161:1-10.