COST-EFFECTIVENESS ANALYSIS OF CYP2B6 GENETIC TESTING TO INFORM EFAVIRENZ DOSE REDUCTION FOR INITIAL HIV THERAPY

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.