TY - JOUR
T1 - Risk of suicidal behavior with use of efavirenz
T2 - Results from the strategic timing of antiretroviral treatment trial
AU - Arenas-Pinto, Alejandro
AU - Grund, Birgit
AU - Sharma, Shweta
AU - Martinez, Esteban
AU - Cummins, Nathan
AU - Fox, Julie
AU - Klingman, Karin L.
AU - Sedlacek, Dalibor
AU - Collins, Simon
AU - Flynn, Patricia M.
AU - Chasanov, William M.
AU - Kedem, Eynat
AU - Katlama, Christine
AU - Sierra-Madero, Juan
AU - Afonso, Claudia
AU - Brouwers, Pim
AU - Cooper, David A.
N1 - Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.
PY - 2018/7/18
Y1 - 2018/7/18
N2 - Background Randomized trials have shown increased risk of suicidality associated with efavirenz (EFV). The START (Strategic Timing of Antiretroviral Treatment) trial randomized treatment-naive human immunodeficiency virus (HIV)-positive adults with high CD4 cell counts to immediate vs deferred antiretroviral therapy (ART). Methods The initial ART regimen was selected prior to randomization (prespecified). We compared the incidence of suicidal and self-injurious behaviours (suicidal behavior) between the immediate vs deferred ART groups using proportional hazards models, separately for those with EFV and other prespecified regimens, by intention to treat, and after censoring participants in the deferred arm at ART initiation. Results Of 4684 participants, 271 (5.8%) had a prior psychiatric diagnosis. EFV was prespecified for 3515 participants (75%), less often in those with psychiatric diagnoses (40%) than without (77%). While the overall intention-to-treat comparison showed no difference in suicidal behavior between arms (hazard ratio [HR], 1.07, P =.81), subgroup analyses suggest that initiation of EFV, but not other ART, is associated with increased risk of suicidal behavior. When censoring follow-up at ART initiation in the deferred group, the immediate vs deferred HR among those who were prespecified EFV was 3.31 (P =.03) and 1.04 (P =.93) among those with other prespecified ART; (P =.07 for interaction). In the immediate group, the risk was higher among those with prior psychiatric diagnoses, regardless of prespecified treatment group. Conclusions Participants who used EFV in the immediate ART group had increased risk of suicidal behavior compared with ART-naive controls. Those with prior psychiatric diagnoses were at higher risk.
AB - Background Randomized trials have shown increased risk of suicidality associated with efavirenz (EFV). The START (Strategic Timing of Antiretroviral Treatment) trial randomized treatment-naive human immunodeficiency virus (HIV)-positive adults with high CD4 cell counts to immediate vs deferred antiretroviral therapy (ART). Methods The initial ART regimen was selected prior to randomization (prespecified). We compared the incidence of suicidal and self-injurious behaviours (suicidal behavior) between the immediate vs deferred ART groups using proportional hazards models, separately for those with EFV and other prespecified regimens, by intention to treat, and after censoring participants in the deferred arm at ART initiation. Results Of 4684 participants, 271 (5.8%) had a prior psychiatric diagnosis. EFV was prespecified for 3515 participants (75%), less often in those with psychiatric diagnoses (40%) than without (77%). While the overall intention-to-treat comparison showed no difference in suicidal behavior between arms (hazard ratio [HR], 1.07, P =.81), subgroup analyses suggest that initiation of EFV, but not other ART, is associated with increased risk of suicidal behavior. When censoring follow-up at ART initiation in the deferred group, the immediate vs deferred HR among those who were prespecified EFV was 3.31 (P =.03) and 1.04 (P =.93) among those with other prespecified ART; (P =.07 for interaction). In the immediate group, the risk was higher among those with prior psychiatric diagnoses, regardless of prespecified treatment group. Conclusions Participants who used EFV in the immediate ART group had increased risk of suicidal behavior compared with ART-naive controls. Those with prior psychiatric diagnoses were at higher risk.
KW - HIV
KW - efavirenz
KW - suicidal behavior
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U2 - 10.1093/cid/ciy051
DO - 10.1093/cid/ciy051
M3 - Article
C2 - 29538636
AN - SCOPUS:85048860458
SN - 1058-4838
VL - 67
SP - 420
EP - 429
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 3
ER -