Efavirenz for Initial Therapy of HIV Associated with Increased Suicide Risk

July 31, 2014

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.

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.