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.
S. Bellamy, None
X. Han, None
G. P. Bisson, None
R. Gross, None