More evidence shows Sustiva increases risk for suicidal behavior

Patients with HIV on a Sustiva-containing ART regimen had a threefold increased risk for suicidal behavior compared with ART-naive patients, according to recent data published in Clinical Infectious Diseases.

The study supports a previous meta-analysis of four AIDS Clinical Trials Group studies that also found an increased risk for suicidality in patients who were randomly assigned to Sustiva (efavirenz [EFV], Bristol-Myers Squibb) vs. those assigned to treatment without EFV (HR = 2.28; 95% CI, 1.27-4.01). However, the data contradict results of two recent observational studies published in 2016 and 2017 that did not find a strong association.

“Several observational studies found no associations of EFV with suicidality, possibly because, consistent with some prescribing guidelines, providers avoided EFV in patients who were at increased risk of suicidality, resulting in a higher proportion of high-risk participants in non-EFV control groups, which might bias observational studies,” Alejandro Arenas-Pinto, MD, of the Medical Research Council Clinical Trials Unit at the University College London, and colleagues wrote.

For their study, Arenas-Pinto and colleagues set out to clarify whether EFV increases suicidal behavior risk more than other HIV drugs using data from the START trial, which randomly assigned patients with HIV to immediate or deferred treatment based on their CD4 cell counts. They compared the incidence of suicidal behavior in the immediate vs. deferred treatment groups overall, then conducted two subanalyses in patients who were prespecified to receive EFV or another ART regimen.

Approximately 75% of the 4,684 participants in the START trial received EFV. These participants were less likely to have pre-existing psychiatric diagnoses compared with those who did not receive EFV (3.1% vs. 13.9%).

Although there was no significant difference in suicidal behavior events in the immediate vs. deferred groups overall, participants who started therapy with EFV had a higher risk than patients in the deferred arm who did not yet start ART (HR = 3.31; 95% CI, 1.1-9.9). There was no excess risk for suicidal behavior in patients assigned to another ART regimen, according to the researchers.

The strongest predictor of suicidal behavior among patients who initiated treatment was a prior psychiatric diagnosis (P = .001). This association was observed in all patients on ART regardless of EFV exposure.

“Given the higher absolute risk of suicidal behavior among those with psychiatric conditions, the association between EFV exposure and suicidal behavior supports the recommendation in national and regional guidelines to avoid prescribing EFV for patients with past or current psychiatric conditions,” Arenas-Pinto and colleagues concluded. “Therefore, screening for major psychiatric conditions before EFV initiation would be advisable.” – by Stephanie Viguers

References:

Arenas-Pinto A, et al. Clin Infect Dis. 2018;doi:10.1093/cid/ciy051.

Bengtson AM, et al. J Acquir Immune Defic Syndr. 2017; doi:10.1097/QAI.0000000000001510.

Mollan K, et al. Ann Intern Med. 2014;doi:10.7326/M14-0293.

Nkhoma ET, et al. Medicine (Baltimore). 2016;doi:10.1097/MD.0000000000002480.

Disclosures: Arenas-Pinto reports receiving grants from Janssen-Cilag, Pfizer and ViiV Healthcare for research outside of the submitted work. Please see the study for all other authors’ relevant financial disclosures.

Patients with HIV on a Sustiva-containing ART regimen had a threefold increased risk for suicidal behavior compared with ART-naive patients, according to recent data published in Clinical Infectious Diseases.

The study supports a previous meta-analysis of four AIDS Clinical Trials Group studies that also found an increased risk for suicidality in patients who were randomly assigned to Sustiva (efavirenz [EFV], Bristol-Myers Squibb) vs. those assigned to treatment without EFV (HR = 2.28; 95% CI, 1.27-4.01). However, the data contradict results of two recent observational studies published in 2016 and 2017 that did not find a strong association.

“Several observational studies found no associations of EFV with suicidality, possibly because, consistent with some prescribing guidelines, providers avoided EFV in patients who were at increased risk of suicidality, resulting in a higher proportion of high-risk participants in non-EFV control groups, which might bias observational studies,” Alejandro Arenas-Pinto, MD, of the Medical Research Council Clinical Trials Unit at the University College London, and colleagues wrote.

For their study, Arenas-Pinto and colleagues set out to clarify whether EFV increases suicidal behavior risk more than other HIV drugs using data from the START trial, which randomly assigned patients with HIV to immediate or deferred treatment based on their CD4 cell counts. They compared the incidence of suicidal behavior in the immediate vs. deferred treatment groups overall, then conducted two subanalyses in patients who were prespecified to receive EFV or another ART regimen.

Approximately 75% of the 4,684 participants in the START trial received EFV. These participants were less likely to have pre-existing psychiatric diagnoses compared with those who did not receive EFV (3.1% vs. 13.9%).

Although there was no significant difference in suicidal behavior events in the immediate vs. deferred groups overall, participants who started therapy with EFV had a higher risk than patients in the deferred arm who did not yet start ART (HR = 3.31; 95% CI, 1.1-9.9). There was no excess risk for suicidal behavior in patients assigned to another ART regimen, according to the researchers.

The strongest predictor of suicidal behavior among patients who initiated treatment was a prior psychiatric diagnosis (P = .001). This association was observed in all patients on ART regardless of EFV exposure.

“Given the higher absolute risk of suicidal behavior among those with psychiatric conditions, the association between EFV exposure and suicidal behavior supports the recommendation in national and regional guidelines to avoid prescribing EFV for patients with past or current psychiatric conditions,” Arenas-Pinto and colleagues concluded. “Therefore, screening for major psychiatric conditions before EFV initiation would be advisable.” – by Stephanie Viguers

References:

Arenas-Pinto A, et al. Clin Infect Dis. 2018;doi:10.1093/cid/ciy051.

Bengtson AM, et al. J Acquir Immune Defic Syndr. 2017; doi:10.1097/QAI.0000000000001510.

Mollan K, et al. Ann Intern Med. 2014;doi:10.7326/M14-0293.

Nkhoma ET, et al. Medicine (Baltimore). 2016;doi:10.1097/MD.0000000000002480.

Disclosures: Arenas-Pinto reports receiving grants from Janssen-Cilag, Pfizer and ViiV Healthcare for research outside of the submitted work. Please see the study for all other authors’ relevant financial disclosures.