911
Genetic Testing in HIV Care: Clinical Effect and Cost-effectiveness of HLA-B*5701 Screening to Guide First-line Abacavir Use
Bruce Schackman*1, C Scott2, R Walensky2,3,4, E Losina2,3,5, K Freedberg2,4,5,6, and P Sax3,4
1Weill Med Coll of Cornell Univ, New York, NY, US; 2Massachusetts Gen Hosp, Boston, US; 3Brigham and Women`s Hosp, Boston, MA, US; 4Harvard Med Sch, Boston, MA, US; 5Boston Univ Sch of Publ Hlth, MA, US; and 6Harvard Sch of Publ Hlth, Boston, MA, US
Background: Pharmacogenetic testing for HLA-B*5701
before abacavir (ABC) therapy reduces the risk of hypersensitivity reactions;
knowledge of test results also leads to fewer unconfirmed hypersensitivity
reactions diagnoses in patients testing HLA-B*5701 negative. We evaluated the
clinical effect and cost-effectiveness of HLA-B*5701 testing before using ABC
in first-line ART regimens.
Methods: We used a widely published simulation model
of HIV disease (CEPAC) to compare 3 first-line fixed-dose NRTI strategies: ABC/3TC
without testing; ABC/lamivudine (3TC) with testing; and tenofovir (TDF)/emtricitibine
(FTC) (with or without testing in case of NRTI substitution). We estimated the
efficacy, side effects (including mild, serious, and fatal ABC hypersensitivity
reactions, and severe TDF nephrotoxicity), and cost of each strategy. Data from
PREDICT-1 provided the base case prevalence of HLA-B*5701 (5.7%) and
probabilities of confirmed hypersensitivity reactions (2.7%) and unconfirmed hypersensitivity
reactions (3.4 to 5.1%). We assumed similar virologic efficacy (81% HIV RNA
<400 copies/mL at 48 weeks), but lower monthly costs for ABC/3TC ($716) vs
TDF/FTC ($724). HLA-B*5701 test cost ($68) was from Medicare and was varied
widely in sensitivity analyses.
Results: The strategy of ABC/3TC without HLA-B*5701
testing results in projected 16.04 discounted quality-adjusted life years and a
discounted lifetime cost of $492,800 per person. HLA-B*5701 testing adds 0.04
quality-adjusted months at an incremental discounted lifetime cost of $120,
resulting in a cost-effectiveness ratio of $40,000/ quality-adjusted life years
for testing than no testing. Starting with TDF/FTC increases costs, with a cost
effectiveness ratio>$100,000/ quality-adjusted life years compared to
initial ABC/3TC with testing. Initial ABC/3TC with testing remains preferred to
initiating with TDF/FTC as long as ABC/3TC costs less per month than TDF/FTC.
Results are sensitive to the cost of testing and the prevalence of HLA*B5701 (see
the figure).
Conclusions: Pharmacogenetic testing for HLA-B*5701
to guide selection of first-line fixed-dose NRTI is cost-effective as long as
ABC/3TC is as effective and costs less than TDF/FTC. The economic value of
testing depends on the prevalence of HLA-B*5701 and the cost of the test.
|
