October 30, 2013
HIV Patients on Efavirenz Have Increased Risks of Suicidality

San Francisco—Human immunodeficiency virus (HIV) patients starting treatment with efavirenz have more than double the risks of suicidal thoughts, attempted suicide, and death by suicide, according to a recent conference presentation.

Still, the overall risk was fairly low, according to the combined analysis of four AIDS Clinical Trials Group (ACTG) studies presented recently at the ID Week meeting in San Francisco. ID Week is held by the Infectious Diseases Society of America, the Society of Healthcare Epidemiology of America, the Pediatric Infectious Disease Society, and the HIV Medicine Association.

Efavirenz, marketed as Sustiva or Stocrin and also included in the Atripla combination pill, is known to cause central nervous system side-effects that could include abnormal dreams, depression, and anxiety. While cases of suicide have been reported among patients receiving efavirenz therapy, no frequency had been determined, according to the study background.

The combined analysis, led by researchers from the University of North Carolina at Chapel Hill, was designed to estimate the incidence of suicidality and compare the time to suicidality among more than 5,000 treatment-naive adult HIV patients randomly assigned to receive efavirenz-containing or efavirenz-free regimens in ACTG studies conducted between 2001 and 2010. Ideation, attempts or completed suicides were considered suicidality in the studies, which lasted about 3 years.

Within the four trials, efavirenz was tested in combination with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) including zidovudine (AZT, Retrovir), lamivudine (3TC, Epivir), abacavir (Ziagen), emtricitabine (Emtriva), and/or tenofovir (Viread, or with emtricitabine in Truvada). One of the trials combined efavirenz with lopinavir/ritonavir (Kaletra).

The comparison regimens, not including efavirenz, involved NRTIs, lopinavir/ritonavir, or boosted atazanavir (Reyataz) plus two NRTIs.

The retrospective analysis looked at 3,241 study participants randomized to efavirenz-containing regimens and 2,091 assigned to efavirenz-free combinations. Baseline characteristics were similar in the two groups—almost three-quarters of participants were male with a median age of 36-years-old. Most participants, 75%, were from the U.S., with 39% of those white and 36% black. Prior AIDS diagnoses were present in 15% of participants, and 8% had injection-drug-use history.

In addition, one-third had a history of a psychiatric diagnosis or psychiatric medication prescription, and 10% had been prescribed antidepressants.

Researchers found that 47 suicidality events occurred in the efavirenz-containing arms compared with 15 in the efavirenz-free arms during the comparison period, for event rates of 8.08 and 3.66 per 1,000 person-years, respectively. The hazard ratio for suicidality was 2.28—or more than twice the risk—in an intent-to-treat analysis, they note, and the difference was statistically significant.

Incidence of suicidality rose the most within the first 6 months after initiation of antiretroviral therapy, the researchers point out. For patients on efavirenz, the incidence rose steadily, with another jump around 2.5 years. Suicidality levelled off around 30 weeks for the efavirenz-free group but increased around 2 years into the drug regimens.

Overall, there were 17 attempted or completed suicides—as opposed to ideation—among study subjects randomized to efavirenz-containing regimens, compared with five on the efavirenz-free therapies.

Efavirenz-free arms were halted in two of the trials, so researchers looked beyond the primary comparison periods to determine that the total number of attempted or completed suicides reached 27 among efavirenz recipients and seven among those previously in the efavirenz-free arms, for a hazard ratio of 2.60.

In addition to efavirenz use, the greatest increased risk of suicidality was seen with patients younger than 30, those with a history of injection drug use, and those with prior psychiatric diagnosis or use of psychiatric medications.

“Initial treatment with an EFV-containing regimen was associated with a two-fold increase in the hazard of suicidality compared to a regimen without EFV,” the authors caution. “HIV-infected patients treated with EFV should be carefully monitored for suicide risk.”

U.S. Pharmacist Social Connect