Monday, October 20, 2014: 10:00 AM

Bruce R. Schackman, PhD1, David W. Haas, MD2, Sanghee S. Park, MPH3, X. Cynthia Li, BS3 and Kenneth A. Freedberg, MD, MSc3, (1)Weill Cornell Medical College, New York, NY, (2)Vanderbilt University School of Medicine, Nashville, TN, (3)Massachusetts General Hospital, Boston, MA

Purpose: The human genotype CYP2B6 can predict plasma drug levels for the HIV drug efavirenz. We assessed the potential cost-effectiveness of CYP2B6 genetic testing to inform efavirenz dose reduction for initial antiretroviral therapy (ART) in HIV disease.

Method: We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) microsimulation model to project quality-adjusted life expectancy and lifetime costs (2012 US dollars) for initiating efavirenz-based ART with or without CYP2B6 genetic testing. Genotyping of three CYP2B6 polymorphisms identifies patients eligible for reduced dose (200 mg/day in slow metabolizers and 400 mg/day in intermediate metabolizers) rather than standard dose therapy (600 mg/day). We assumed that after genetic testing, 47% of patients would be eligible to reduce from 600 to 400 mg and 13% eligible to reduce from 600 to 200 mg, based on published data. Cost of 600 mg efavirenz was $7,300/year, and for generic efavirenz it was $2,400/year. In sensitivity analyses we varied the probability of toxicity with and without dose reduction, treatment efficacy with dose reduction, population characteristics, and availability of less expensive generic efavirenz. We also considered a universal dose reduction strategy (i.e. no genetic testing) to 400 mg/day for all patients. Costs and quality-adjusted life years (QALYs) were discounted at 3% annually.

Result: Initiating efavirenz-based ART at CD4 counts <500/mm3 without genetic testing had a per person discounted life expectancy of 13.43 QALYs and discounted lifetime cost of $419,600. Genetic testing followed by dose reduction decreased lifetime cost by $16,200 with no change in QALYs, assuming equal efficacy after dose reduction. With no generic efavirenz available, genetic testing remained cost-effective (standard dose versus genetic testing ICER > $100,000/QALY) after dose reduction. With generic efavirenz available, standard dose was preferred if efficacy decreased 9% or more after dose reduction (Figure). In a scenario including a universal dose reduction strategy, universal dose reduction was preferred unless generic efavirenz was available and efficacy decreased 7% or more after dose reduction.  

Conclusion: Genotyping of CYP2B6 may be effective to inform efavirenz dose reduction strategies and lower the cost of HIV therapy. A universal dose reduction strategy could further lower this cost with minimal life expectancy changes. Results depend on the efficacy of reduced dose regimens if generic efavirenz is available.