The cost-effectiveness of HLA-B*5701 genetic screening to guide initial antiretroviral therapy for HIV.
OBJECTIVE
To evaluate the clinical impact and cost-effectiveness of HLA-B*5701 testing to guide selection of first-line HIV regimens in the United States.


METHODS
Cost-effectiveness analysis using a simulation model of HIV disease. The prevalence of HLA-B*5701 and the probabilities of confirmed and unconfirmed severe systemic hypersensitivity reaction among patients taking abacavir testing HLA-B*5701 positive and negative were from the Prospective Randomized Evaluation of DNA Screening in a Clinical Trial study. The monthly costs of abacavir-based and tenofovir-based regimens were $1135 and $1139, respectively; similar virologic efficacy was assumed and this assumption was varied in sensitivity analysis.


METHODS
Simulated cohort of patients initiating HIV therapy.


METHODS
The interventions are first-line abacavir, lamivudine, and efavirenz without pretreatment HLA-B*5701 testing; the same regimen with HLA-B*5701 testing; and first-line tenofovir, emtricitabine, and efavirenz.


METHODS
Quality-adjusted life years and lifetime medical costs discounted at 3% per annum, cost-effectiveness ratios ($/QALY).


RESULTS
Abacavir-based treatment without HLA-B*5701 testing resulted in a projected 30.93 years life expectancy, 16.23 discounted quality-adjusted life years, and $472,200 discounted lifetime cost per person. HLA-B*5701 testing added 0.04 quality-adjusted months at an incremental cost of $110, resulting in a cost-effectiveness ratio of $36,700/QALY compared with no testing. Initiating treatment with a tenofovir-based regimen increased costs without improving quality-adjusted life expectancy. HLA-B*5701 testing remained the preferred strategy only if abacavir-based treatment had equal efficacy and cost less per month than tenofovir-based treatment. Results were also sensitive to the cost of HLA-B*5701 testing and the prevalence of HLA-B*5701.


CONCLUSIONS
Pharmacogenetic testing for HLA-B*5701 is cost-effective only if abacavir-based treatment is as effective and costs less than tenofovir-based treatment.
Schackman
Bruce R
BR
Department of Public Health, Weill Cornell Medical College, New York, New York 10021, USA. brs2006@med.cornell.edu
Scott
Callie A
CA
Walensky
Rochelle P
RP
Losina
Elena
E
Freedberg
Kenneth A
KA
Sax
Paul E
PE
D000225:Adenine / Q000031:analogs & derivatives / Q000191:economics / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000191:economics; D003362:Cost-Benefit Analysis; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use; D016527:Drug Costs / Q000706:statistics & numerical data; D004342:Drug Hypersensitivity / Q000191:economics / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D005260:Female; D005820:Genetic Testing / Q000191:economics* / Q000379:methods; D015658:HIV Infections / Q000188:drug therapy* / Q000191:economics / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D017048:Health Care Costs / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D063065:Organophosphonates / Q000191:economics / Q000627:therapeutic use; D010597:Pharmacogenetics / Q000191:economics; D019057:Quality-Adjusted Life Years; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects; D012680:Sensitivity and Specificity; D000068698:Tenofovir; D016896:Treatment Outcome; D000099227:Abacavir
D000225:Adenine; D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D015235:HLA-B Antigens; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000099227:Abacavir; C484830:HLA-B*57:01 antigen
Pharmacogenomics. 2007 Sep;8(9):1169-78
17924832
N Engl J Med. 2006 Jan 19;354(3):251-60
16421366
J Acquir Immune Defic Syndr. 2006 Oct 1;43(2):153-60
16951643
Lancet. 2002 Mar 2;359(9308):727-32
11888582
Lancet. 2008 Apr 26;371(9622):1417-26
18387667
Clin Infect Dis. 2006 Jul 1;43(1):103-5
16758425
Med Decis Making. 2002 Sep-Oct;22(5 Suppl):S45-57
12369231
AIDS. 2001 Jan 5;15(1):77-85
11192871
Med Care. 2006 Nov;44(11):990-7
17063130
J Virol. 2007 Mar;81(6):3037-41
17192300
Scand J Infect Dis. 2007;39(6-7):486-507
17577810
Clin Infect Dis. 1999 Nov;29(5):1251-6
10524971
N Engl J Med. 2008 Feb 7;358(6):568-79
18256392
Lancet. 2002 Mar 30;359(9312):1121-2
11943262
Clin Ther. 2001 Oct;23(10):1603-14
11726000
JAMA. 2001 Nov 14;286(18):2270-9
11710893
Pharmacogenetics. 2004 Jun;14(6):335-42
15247625
JAMA. 2004 Jul 14;292(2):191-201
15249568
N Engl J Med. 2001 Mar 15;344(11):824-31
11248160
J Acquir Immune Defic Syndr. 2007 May 1;45(1):1-3
17356469
J Acquir Immune Defic Syndr. 2006 Dec 15;43(5):535-40
17057609
Drug Saf. 2006;29(9):811-26
16944966
Clin Infect Dis. 2006 Jul 1;43(1):99-102
16758424