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HIV Drug Therapy: Efavirenz Not Linked to Higher Suicide Risk in D:A:D Cohort

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People taking antiretroviral therapy (ART) regimens containing the NNRTI efavirenz (Sustiva) were not more likely to die due to suicide or psychiatric illness than those taking other drugs in the large D:A:D cohort, researchers reported last month at the HIV Drug Therapy 2014 meeting in Glasgow.

Efavirenz, one of the most widely used HIV medications, is highly effective and generally regarded as safe, but it is known to cause neuropsychiatric or central nervous system side effects such as insomnia, abnormal dreams, anxiety, and dizziness. The drug's association with depression and suicide are less clear and data have been conflicting.

A study presented at IDWeek 2013 found that suicidal thoughts, attempted suicide, and death by suicide were more than twice as common among people with HIV who started treatment with efavirenz in a meta-analysis of 4 ACTG randomized clinical trials (RCTs), but the overall risk was low. At this year's IDWeek, researchers reported that efavirenz use was not associated with a higher rate of suicidal thoughts or attempts in an analysis of claims data from U.S. commercial insurance and Medicaid databases conducted by the drug's manufacturer, Bristol-Myers Squibb.

At the Glasgow meeting Colette Smith from University College London presented findings from a study evaluating the association between efavirenz use and completed suicides.

Unlike the previously reported studies, this one looked only at deaths attributed to suicide or psychiatric illness, not suicidal ideas, thoughts, or attempts. In the ACTG analysis there were significantly more instances of all endpoints combined, but only a trend toward more attempted and completed suicides, since the total number of these events was small (17).

The present analysis used data from nearly 50,000 people with HIV in cohorts participating in the D:A:D (Data Collection on Adverse Events of Anti-HIV Drugs) collaboration in Europe, Australia, and the U.S. All D:A:D participants were prospectively followed from study entry until February 2013, the last study visit, or death, whichever came first.

Using a database that records underlying, immediate, and up to 4 contributing causes of death, the researchers identified deaths that had suicide or psychiatric illness considered as the underlying cause, or as one of the underlying, immediate, or contributing causes.

Results

  • A total of 4420 deaths occurred among 49,717 participants during 371,333 person-years of follow up, a mortality rate of 11.9 per 1000 person-years (PY).
  • 193 of these deaths had suicide or psychiatric illness considered to be the underlying cause, a rate of 0.52 per 1000 PY.
  • 482 deaths had suicide or psychiatric conditions listed among their underlying, immediate, or contributing causes, a rate of 1.30 per 1000 PY.
  • There were no differences in rates of death due to suicide or psychiatric illness according to use of efavirenz or other antiretroviral drugs.
  • There was also no association observed when considering efavirenz use only during the previous 3 or 6 months.
  • However, the highest rate of suicide or psychiatric death was seen among people who were ART-experienced but currently off treatment.
  • There was a strong association between current CD4 T-cell count and deaths due to suicide or psychiatric illness, with rates ranging from 0.95 per 1000 PY among those with >500 cells/mm3 to 3.18 per 1000 PY among people with <200 cells/mm3.
  • Older age, male sex, and history of injection drug use were also associated with higher suicide or psychiatric death rates.
  • Results were consistent when considering suicide alone -- but not other psychiatric conditions -- as the underlying cause of death.
  • They remained consistent when looking at suicide plus possibly related causes of death including psychiatric illness, drug overdose, alcohol-related death, or accidental or violent death.

"The finding of no higher death rates from suicide amongst those receiving efavirenz is reassuring," the researchers concluded.

"However, there is likely confounding by indication in our observational study," they cautioned. "In light of conflicting results from RCTs, this potentially could suggest that in clinical practice efavirenz may be less frequently prescribed in those with underlying psychiatric conditions."

Smith stressed that while these findings offer reassurance that efavirenz as currently used is not significantly increasing the risk of suicide, they do not indicate that there is a lack of an association between efavirenz and suicide.

12/9/14

Reference

C Smith, L Ryom, A d’Arminio Monforte, et al. Lack of association between use of efavirenz and death from suicide: evidence from the D:A:D study. HIV Drug Therapy 2014. Glasgow, November 2-6, 2014. Abstract O315.