1520. Does Slow Efavirenz Metabolism Have Greater Impact on Outcomes of Older HIV+ Africans?
Session: Poster Abstract Session: HIV: Antiretroviral Therapy
Friday, October 28, 2016
Room: Poster Hall
Posters
  • Torgersen_Poster 1520_IDWeek 2016.pdf (356.9 kB)
  • Background: Neurotoxicity occurs frequently in people taking efavirenz (EFV), a medication commonly used in resource-limited settings. The cognitive and neuroanatomical changes that occur with advancing age may potentiate these neurotoxic effects in older age, but few data on antiretroviral treatment (ART) toxicity come from sub-Saharan Africa. Certain CYP2B6 polymorphisms are associated with slower EFV metabolism and may also interact with age to increase risk of poor outcomes in this population.

    Methods: We examined associations between age, CYP2B6 polymorphisms, and clinical outcomes among a cohort of 940 HIV+ adults initiating EFV-based ART in Botswana between 2010 and 2013. Older age was defined as age ≥50 years. CYP2B6 G516T polymorphisms were defined as normal, intermediate, and slow metabolism. Neurotoxicity was measured through a symptom severity questionnaire. Age-stratified univariate and multivariate logistic regression were performed to identify factors associated with clinical outcomes in active follow-up and to examine interaction.

    Results: Older age was associated with death (OR: 2.70, 95% CI: 1.31-5.60), loss to care (OR: 2.05, 95% 1.31-5.60), but not virologic failure (OR: 0.71, 95% CI: 0.34-1.48). Older age was not associated with increased EFV-associated neurotoxicity. In univariate analysis, slow efavirenz metabolism increased risk of virologic failure (OR: 2.22, 95% CI: 1.18- 4.19) but not loss to care (OR 1.33, 95% CI: 0.83-2.12). However, age modified the effect of CYP2B6 polymorphism on loss to care with older, slow metabolizers at higher risk than older, normal metabolizers (OR: 7.24, 95% CI: 2.16-24.30) while younger, slow metabolizers had no increased risk compared to younger, normal metabolizers (OR: 1.03, 95% CI: 0.61-1.74; Wald test of interaction: p=0.017).

    Conclusion: Older age was associated with loss to care, especially among older patients with slow EFV metabolism; although, subjective toxicity was rare overall. Understanding the pharmacodynamic relationship between older age and CYP2B6 polymorphisms will be important to improve outcomes in an aging population initiating EFV-based ART in similar settings.

    Jessie Torgersen, MD, MHS, Division of Infectious Diseases, University of Pensylvania Perelman School of Medicine, Philadelphia, PA, Athena Zuppa, MD, MSCE, Anesthesiology and Critical Care, The Children's Hospital of Philadelphia, Philadelphia, PA, Scarlett Bellamy, ScD, Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, Xiaoyan Han, MS, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, Gregory P. Bisson, MD, MSCE, Department of Medicine, Division of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia, PA and Robert Gross, MD, MSCE, Department of Medicine, Division of Infectious Disease, University of Pensnylvania Perelman School of Medicine, Philadelphia, PA

    Disclosures:

    J. Torgersen, None

    A. Zuppa, None

    S. Bellamy, None

    X. Han, None

    G. P. Bisson, None

    R. Gross, None

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