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.

Abstract

BACKGROUND:

The relationship between efavirenz use and suicidality is not well-defined.

OBJECTIVE:

To compare time to suicidality with efavirenz-containing versus efavirenz-free antiretroviral regimens for initial treatment of HIV.

DESIGN:

Participant-level data were analyzed from 4 AIDS Clinical Trials Group, antiretroviral-naive studies conducted from 2001 to 2010. Within each study, participants were randomly assigned to an efavirenz-containing (n = 3241) or efavirenz-free (n = 2091) regimen. (ClinicalTrials.gov: NCT00013520 [A5095], NCT00050895 [A5142], NCT00084136 [A5175], and NCT00118898 [A5202]).

SETTING:

AIDS Clinical Trials Group sites; 74% of participants enrolled in the United States.

PATIENTS:

Antiretroviral-naive participants.

INTERVENTION:

Efavirenz versus efavirenz-free regimens.

MEASUREMENTS:

Suicidality was defined as suicidal ideation or attempted or completed suicide. Groups were compared with a hazard ratio and 95% CI estimated from a Cox model, stratified by study.

RESULTS:

Seventy-three percent of participants were men, the median age was 37 years, and 32% had documented psychiatric history or received psychoactive medication within 30 days before entering the study. Median follow-up was 96 weeks. Suicidality incidence per 1000 person-years was 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). 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). Eight suicides in the efavirenz group and 1 in the efavirenz-free group were reported.

LIMITATION:

There was not a standardized questionnaire about suicidal ideation or attempt. Efavirenz was open-label in 3 of 4 studies.

CONCLUSION:

Initial treatment with an efavirenz-containing antiretroviral regimen was associated with a 2-fold increased hazard of suicidality compared with a regimen without efavirenz.

PRIMARY FUNDING SOURCE:

National Institutes of Health.

• Authors: Katie R Mollan, Marlene Smurzynski, Joseph J Eron, Eric S Daar, Thomas B Campbell, Paul E Sax, Roy M Gulick, Lumine Na, Lauren O'Keefe, Kevin R Robertson, Camlin Tierney
• Journal: Annals of internal medicine (Ann Intern Med) Vol. 161 Issue 1 Pg. 1-10 (Jul 01 2014) ISSN: 1539-3704 [Electronic] United States
• PMID: 24979445 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Alkynes
• Anti-Retroviral Agents
• Benzoxazines
• Cyclopropanes
• RNA, Viral
• efavirenz

Topics

• Adult
• Alkynes
• Anti-Retroviral Agents (adverse effects)
• Benzoxazines (adverse effects)
• Cause of Death
• Cyclopropanes
• Female
• Follow-Up Studies
• HIV Infections (drug therapy, mortality)
• HIV-1 (genetics, isolation & purification)
• Humans
• Male
• RNA, Viral (analysis)
• Randomized Controlled Trials as Topic
• Suicidal Ideation
• Suicide (statistics & numerical data)
• Suicide, Attempted (statistics & numerical data)
• Viral Load