Transportability From Randomized Trials to Clinical Care: On Initial HIV Treatment With Efavirenz and Suicidal Thoughts or Behaviors.

Abstract

In an analysis of randomized trials, use of efavirenz for treatment of human immunodeficiency virus (HIV) infection was associated with increased suicidal thoughts/behaviors. However, analyses of observational data have found no evidence of increased risk. To assess whether population differences might explain this divergence, we transported the effect of efavirenz use from these trials to a specific target population. Using inverse odds weights and multiple imputation, we transported the effect of efavirenz on suicidal thoughts/behaviors in these randomized trials (participants were enrolled in 2001-2007) to a trials-eligible cohort of US adults initiating antiretroviral therapy while receiving HIV clinical care at medical centers between 1999 and 2015. Overall, 8,291 cohort participants and 3,949 trial participants were eligible. Prescription of antidepressants (19% vs. 13%) and injection drug history (16% vs. 10%) were more frequent in the cohort than in the trial participants. Compared with the effect in trials, the estimated hazard ratio for efavirenz on suicidal thoughts/behaviors was attenuated in our target population (trials: hazard ratio (HR) = 2.3 (95% confidence interval (CI): 1.2, 4.4); transported: HR = 1.8 (95% CI: 0.9, 4.4)), whereas the incidence rate difference was similar (trials: HR = 5.1 (95% CI: 1.6, 8.7); transported: HR = 5.4 (95% CI: -0.4, 11.4)). In our target population, there was greater than 20% attenuation of the hazard ratio estimate as compared with the trials-only estimate. Transporting results from trials to a target population is informative for addressing external validity.

• Authors: Katie R Mollan, Brian W Pence, Steven Xu, Jessie K Edwards, W Christopher Mathews, Conall O'Cleirigh, Heidi M Crane, Ellen F Eaton, Ann C Collier, Ann Marie K Weideman, Daniel Westreich, Stephen R Cole, Camlin Tierney, Angela M Bengtson, CFAR Network of Integrated Clinical Systems and the AIDS Clinical Trials Group
• Journal: American journal of epidemiology (Am J Epidemiol) Vol. 190 Issue 10 Pg. 2075-2084 (10 01 2021) ISSN: 1476-6256 [Electronic] United States
• PMID: 33972995 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Alkynes
• Anti-HIV Agents
• Antidepressive Agents
• Benzoxazines
• Cyclopropanes
• efavirenz

Topics

• Adult
• Alkynes (adverse effects)
• Anti-HIV Agents (adverse effects)
• Antidepressive Agents (therapeutic use)
• Benzoxazines (adverse effects)
• Cyclopropanes (adverse effects)
• Depression (chemically induced, drug therapy, epidemiology)
• Drug Prescriptions (statistics & numerical data)
• Female
• HIV
• HIV Infections (drug therapy)
• Humans
• Incidence
• Male
• Observational Studies as Topic
• Proportional Hazards Models
• Randomized Controlled Trials as Topic
• Suicidal Ideation
• Translational Research, Biomedical (methods)
• United States (epidemiology)