Transcript Dollars and Sense: Cost-Effectiveness in Clinical Medicine - HIV-DRI

HIV Resistance Testing:
Overview of Indications and Cost
Issues
Paul E. Sax, MD
Division of Infectious Diseases
Brigham and Women’s Hospital
Harvard Medical School
Disclosures
• Consultant: Abbott, BMS, Gilead, GSK
• Honoraria for teaching: Abbott, BMS, Gilead,
GSK, Merck, Tibotec, Virco
• Grant Support: BMS, Pfizer, Merck
Outline
• Review of available resistance tests
• What tests to order when
• Review of cost analyses
• How cost issues relate to resistance testing
– USA and other developed countries
– Resource-limited settings
When to Use Resistance Testing
IAS-USA[1]
DHHS[2]
European[3]
Primary/acute
Recommend
Recommend
Recommend
Postexposure
prophylaxis
—
—
Recommend
Consider*
Recommend
Strongly consider*
Failure
Recommend
Recommend
Recommend
Pregnancy
Recommend
—
Recommend*
—
—
Recommend†
Chronic, Rx naïve
Pediatric
*Especially if exposure to someone receiving antiretroviral drugs is likely or if prevalence of
drug resistance in untreated patients ≥ 5% (European: ≥10%).
1. Hirsch et al. Clin Infect Dis. 2003;37:113-28.
2. Available at: http://www.aidsinfo.nih.gov. Accessed May 4, 2006.
3. Vandamme et al. Antivir Ther. 2004;9:829-48.
Genotype Preferred
• Acute (primary) HIV infection
• Treatment-naïve
• Failure of first regimen
• Little or no prior resistance documented
• Patient no longer on therapy
Phenotype, Virtual Phenotype,
or Combined Pheno/genotype Preferred
• High-level resistance to NRTIs or PIs on genotype
• Multiple regimen failure with limited treatment options
• Viral tropism assay needed (phenotype only)
Cost Issues in Resistance Testing
Who Decides if a Test is
Indicated? Should be Reimbursed?
• Clinician and/or patient?
• Medicaid or ADAP or VA?
• Insurance companies?
– Kaiser or BC/BS or Harvard University Health Plan?
• USPHS or IAS or WHO guidelines?
• Resistance testing vendors?
• “Society”?
Antiretroviral & Prophylaxis Costs:
United States
Zidovudine
$3,300 TMP-SMX
$
105
Tenofovir
$5,500 Dapsone
$
60
Lamivudine
$4,000 Atovaquone
$ 9,560
Indinavir
$7,000 Azithromycin
$ 1,450
Nelfinavir
$9,125 Fluconazole
$
Efavirenz
$5,900 Ganciclovir
$15,600
Lopinavir/r
$8,500 Enfuvirtide
$20,000
*Wholesale cost per person for one year
510
Resources are Limited
– Even Here (USA)
• Coverage in AIDS Drug Assistance Programs varies
widely by state/territory
– 35/54: all antiretrovirals covered
– 25/54: HCV treatment covered
– 21/54: Hep A and Hep B vaccines covered
• As of March 2007, four ADAPs had waiting lists for
antiretrovirals (571 individuals)
• Eight states initiated other cost-containment measures
in the past fiscal year, three more expected in FY 2007
Source: National ADAP Monitoring Project Annual Report
http://www.kff.org/hivaids/upload/7619ES.pdf, April 2007
Question:
How has effective antiretroviral therapy
influenced the cost of HIV care?
Costs are down due to reduced opportunistic infections
and hospitalizations.
Costs are up due to the cost of antiretroviral medications
and prolonged survival.
Costs are unchanged, as these two forces balance each
other.
Cost Timeline with Significant
Drug Release Dates
$1,000,000
$900,000
ONGOING IN 1994:
ddI, ddC, AZT
EFAVIRENZ
$800,000
DELAVIRDINE
$700,000
NELFINAVIR
$600,000
HOSPITAL COSTS
$500,000
NEVIRAPINE
$400,000
INDINAVIR
$300,000
$200,000
$100,000
D4T
$0
RITONAVIR
3TC
SAQUINAVIR
ANTIVIRAL COSTS
Cost Analyses: HIV Care
is Becoming More Expensive
• What does it cost/year to care for an HIV patient in the
USA?
–
–
–
–
HCSUS,1992:
HCSUS, 1998:
Johns Hopkins, 1999:
CEPAC Collaboration, 2004:
$14,700
$20,000
$15,660
$26,800
• What is the lifetime cost?
– 1992:
– 2004:
$100,000 (survival 6.8 years)
$649,000 (survival 24.2 years)
Bozzette et al. NEJM 1998;339:1897-904.
Gebo et al. AIDS 1999;13:963-9.
Schackman et al. Med Care. 2006;44:990-7.
Cost-benefit Analysis
“I’ve received your credit report, and you seem to
be a person worth saving.”
Cost-effectiveness Analysis
• Two different outcome measures:
– Cost in dollars
– Effectiveness: years of life saved (YLS) or qualityadjusted life years (QALY)
• Cost-effectiveness ratio:
– Resource use ($)/Health benefit (QALY)
The “$50,000” Threshold:
Often Cited, Often Ignored
$/YLS
Propranolol, mild HTN
14,000
TPA vs streptokinase
33,000
Rx hypercholesterolemia
47,000
Dialysis, ESRD
51,000
Screening mammography:
Annual 50-69
Annual 40-49
YLS = years of life saved
57,500
168,400
Antiretroviral Therapy is
Very Cost Effective
C-E Ratio
Strategy
Costs ($)
QALM
($/QALY)
No ART
59,790
47.52
---
AZT/3TC/EFV
94,290
79.56
13,000
No ART
54,150
35.04
---
AZT/3TC/IDV
80,460
53.16
17,000
Dupont 006 (CD4 350)
Johns Hopkins (CD4 217)
Freedberg et al. NEJM 2001;344:824-31.
What Does HIV Lab Testing Cost?
Test
HIV RNA
CD4
Costs in $
119
83
Genotype
“Virtual” phenotype
Phenotype
Phenotype + genotype
Tropism assay
355-676
550
700-1148
800-1690
1960
Sources: BWH hospital lab, private vendors
Resistance Testing is
Cost-effective after Treatment Failure
QualityAdjusted Life
Expectancy†
Costs†
CostEffectiveness
Ratio‡
mo
$
$/QALY gained
No genotypic
antiretroviral resistance testing§
60.9
90 360
–
Genotypic antiretroviral resistance
testing
63.1
93 650
17 900
No genotypic
antiretroviral resistance testing
62.2
91 980
–
Genotypic antiretroviral resistance
testing
66.4
97 790
16 300
Trial (Reference)
CPCRA 046 (10)
VIRADAPT (6)
Separate study: 22,510 euros/life-year gained.
Weinstein et al. Ann Int Med. 2001;134:440-50.
Corzillius et al. Antivir Ther. 2004;9:27-36.
Resistance Testing at Diagnosis
Improves Outcome at Reasonable Cost
Test cost of $400
Prevalence of
primary
resistance in
population, %
Cost-effectiveness by test cost, $/QALY
Incremental
cost,$
Life
expectancy
gained,
QALMs
$400
$200
$800
0.25
430
0.03
175,400
97,200
331,500
0.5
480
0.06
97,300
58,200
175,400
1.0
580
0.1
58,300
38,700
97,300
1.5
670
0.2
45,200
32,200
71,300
3.0
950
0.4
32,200
25,700
45,200
5.0
1300
0.6
27,000
23,100
34,800
7.0
1700
0.8
24,800
22,000
30,400
8.3a
2000a
1.0a
23,900a
21,600a
28,600a
9.0
2100
1.1
23,600
21,400
27,900
10.0
2300
1.2
23,100
21,200
27,000
Sax et al. Clin Infect Dis. 2005; 41:1316-23.
Genotype versus
Phenotype + Genotype
Description
GT
PTGT
Costs
$160,040
$161,299
QALYs
4.54
4.59
$35,326
$35,175
Cost per QALY
ICER, PTGT to GT
$28,812 per QALY
ICER = Incremental Cost-Effectiveness Ratio
•
Results
– Costs of GT strategy slightly lower than PTGT
– Survival longer with PTGT
– Incremental CE ratio = $28,812/QALY
•
Limitations:
– benefits of PTGT over GT likely to be much smaller in those with limited
resistance
– Industry-sponsored
Coakley et al. ICAAC 2005, Abstract #H1054
Resistance Issues in
ResourceLimited Settings
HIV Drug Resistance is
Becoming More Important in
Resource-Limited Settings
• Treatment started with more
advanced disease
• Fewer agents available
• Some older treatments have
long-term toxicity that reduces
adherence
• Supply chain for medications
inconsistent
• Viral load usually not used for
monitoring  prolonged
treatment with virologic failure
• Resistance testing not
available
Hospital laboratory, Rwanda
(Photo courtesy W Rodriguez)
How to Select MDR HIV:
Lessons from the Past
Highly adherent, aggressively treated
patients with non-suppressive
regimens led to selection of
multidrug-resistant HIV
Sequential NRTI
monotherapy and
dual-NRTI therapy
No
ART
ZDV
monotherapy
Early
80s
Late
80s
“Hit hard,
hit early”
Earlier initiation
of therapy with
better rx
“Sequential
monotherapy”
with PIs/NNRTIs
Early
90s
Mid
90s
Deferral
of therapy
Late
90s
Early
00s
Late
00s
Question:
In which of the following countries would
resistance testing be offered as part of
standard of care to all patients with virologic
failure on their first regimen?
Argentina
Botswana
Brazil
South Africa
Vietnam
Where is Resistance
Testing Being Performed in
Resource-Limited Settings?
• Brazil
– Available at all sites after panel reviews indication
• Botswana
– Limited access; recommended for “second-line”
treatment failure
• All other sites surveyed
– Highly-limited access (e.g., private payors only) or no
access at all
Schechter M, Shapiro R, Rodriguez W, Marconi V,
Haubrich R, Cahn P, Antunes F, Libman H, Eisenberg
M, Cosimi L, Mayer K. Personal communications.
WHO Guidelines: Only Mention
of Clinical Use of Resistance Testing
“For highly treatment experienced patients, individual
management is necessarily tailored to the availability of
alternative ARVs, for which there is very limited provision
in the public sector in resource-limited settings, and to
additional laboratory investigations, such as individual
drug resistance testing.”
Antiretroviral Therapy For HIV Infection In Adults
And Adolescents, WHO, 2006 Revision
Question:
Which of the following novel technologies
do you think is most likely to be available
and widely adopted 5 years from now?
High sensitivity genotyping for minority variants
Rapid, low-cost screening for CCR5 vs CXCR5 viral
tropism
Genotype and/or phenotype testing for resistance to
CCR5 antagonists
Genotype and/or phenotype testing for resistance to
integrase inhibitors
None will be widely adopted