Conference Coverage

Antiretroviral efavirenz linked to increased suicidality


 

AT AIDS 2016

References

DURBAN, SOUTH AFRICA – The use of efavirenz in HIV-infected participants in the landmark START trial was associated with significantly increased risk of suicidal behavior, Alejandro Arenas-Pinto, MD, reported at the 21st International AIDS Conference.

“The impact of efavirenz exposure was particularly high in those with a prior psychiatric diagnosis,” according to the infectious diseases specialist. “The message here is that it’s probably just those patients with preexisting neuropsychiatric conditions who are at higher risk of suicidal behavior, according to our data. This supports a recommendation to screen for preexisting depression and other neuropsychiatric conditions before efavirenz initiation.”

Dr. Alejandro Arenas-Pinto Bruce Jancin/Frontline Medical News

Dr. Alejandro Arenas-Pinto

START was a clinical practice-transforming randomized trial that established a clear clinical benefit for a strategy of initiating antiretroviral therapy immediately upon diagnosis of HIV infection in asymptomatic adults instead of waiting until their CD4+ count drops below the level of 350 cells/mm3 (N Engl J Med. 2015 Aug 27;373[9]:795-807). Immediate antiretroviral therapy (ART) was associated with a 57% reduction in the risk of the primary outcome, a composite comprised of serious AIDS-defining events, serious non-AIDS adverse events, and all-cause mortality.

Once the results were in, however, Dr. Arenas-Pinto and the other START investigators quickly noticed that suicidal behavior was the second-most-common serious non-AIDS event observed in the study. A total of 57 patients were affected, for a rate of 0.36 events per 100 person-years of follow-up. There were 30 suicide attempts, 16 cases of suicidal ideation, 3 completed suicides, and 1 case each classified as intentional self-injury or self-injurious ideation. A closer look was warranted, said Dr. Arenas-Pinto of University College London.

The investigators next determined that the risk of suicidal behavior was significantly higher in the 3,516 START participants on efavirenz than in the 1,169 subjects on other ART drugs. The risk was 4.2-fold greater in patients who started on efavirenz immediately than in those randomized to begin the drug on a deferred basis. In contrast, suicidal behavior was no more frequent in patients who started on other ART medications immediately than if treatment was deferred.

In a multivariate Cox proportional hazards analysis of predictors of suicidal behavior in patients on efavirenz, the stand-out predictor was prior diagnosis of major depression, bipolar disorder, or schizophrenia or another psychotic disorder, with an associated 12.8-fold increased risk. Heavy alcohol use was associated with a 6.1-fold increased risk and ever having used recreational drugs conferred a 2.9-fold increased risk. In contrast, the risk of suicidal behavior in patients on efavirenz dropped sharply with advancing age.

Efavirenz is a non-nucleoside transcriptase inhibitor marketed as Sustiva, or when incorporated into once-daily, fixed-dose, triple-drug therapy with tenofovir/emtricitabine, as Atripla.

The labeling for efavirenz states that many of the drug’s more common side effects involve the brain. They include dizziness, insomnia, depression, anxiety, nightmares, hallucinations, delusions, and confusion.

The START study was funded by the National Institutes of Health. Dr. Arenas-Pinto reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

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