Correspondence
The Cost Effectiveness of Antiretroviral Therapy for HIV Disease
N Engl J Med 2001; 345:68-69July 5, 2001
- Article
To the Editor:
The study by Freedberg et al. (March 15 issue)1 compared a three-drug regimen with no antiretroviral therapy in patients infected with the human immunodeficiency virus (HIV) and found the regimen to be effective. One weakness of this study is that no treatment was chosen as the reference category. There were no comparisons between triple therapy and double therapy or between triple therapy and monotherapy. Studies of cost effectiveness should be guided by clinical research, and the controlled studies in the analysis by Freedberg et al. did not include untreated groups. Since withholding treatment is unethical, the design of the study is incorrect and its results are misleading.
We estimated the quality-adjusted life expectancy with zidovudine monotherapy as 2.03 years with an annual discount rate of 3 percent.2 The quality-adjusted gain in life expectancy found by Freedberg et al. was 1.38 years, which was calculated, with an annual discount rate of 3 percent, as the difference between 2.91 additional years with triple therapy and 1.53 additional years with no treatment. This gain was large because the reference category was no treatment. If monotherapy is used for comparisons, the gain in life expectancy becomes a much less impressive 0.88 year (2.91 minus the 2.03 years from our estimate), and the analysis of cost effectiveness will yield quite different results. The gain becomes even smaller if double therapy is used as the reference category.
2 ReferencesAndrea Messori, Pharm.D.
Sabrina Trippoli, Pharm.D.
Monica Vaiani, Pharm.D.
Laboratorio di Farmacoeconomia, 50134 Florence, Italy
md3439@mclink.it 1
Freedberg KA ,Losina E ,Weinstein MC , et al. The cost effectiveness of combination antiretroviral therapy for HIV disease. N Engl J Med 2001;344:824-831
Full Text | Web of Science | Medline2
Messori A ,Becagli P ,Berto V , et al. Advanced HIV infection treated with zidovudine monotherapy: lifetime values of absolute cost-effectiveness as a pharmacoeconomic reference for future studies evaluating antiretroviral combination treatments. Ann Pharmacother 1997;31:1447-1454
Web of Science | Medline
To the Editor:
The cost effectiveness of combination antiretroviral therapy for HIV-infected patients in the United States, as reported by Freedberg and associates, was important to document. However, over 90 percent of HIV infections occur elsewhere, in the developing world. Recently, attention has focused on the cost of antiretroviral drugs and their distribution; these economic analyses will need to be considered by those advocating widespread use of antiretroviral therapy in the developing world. As Freedberg et al. noted, current antiretroviral therapy extends the lives of HIV-infected patients by only a few years. Viral resistance and adverse effects of the drugs undermine their utility.
Strategies to mitigate the failure of antiretroviral therapy, such as testing for resistance and monitoring of compliance, were not included in their survey. Because of the public health consequences, such procedures should be an integral part of the discussion of the economic aspects of HIV and AIDS. The recent calls for wide distribution of antiretroviral therapy, in Africa and other parts of the world being decimated by HIV, could be acted on without adequate oversight.
A total of 5.8 percent of patients newly infected with HIV in the United States and Canada have strains resistant to two classes of anti-HIV drugs, as compared with just 0.4 percent six years ago.1 One in seven newly infected persons in the United States now acquires a strain resistant to at least one class of antiviral agents.1 Many factors may facilitate such resistance, but noncompliance of patients and drug interactions are key and, given existing economic limitations, can only exacerbate the situation in the developing world.
1 ReferencesJeffrey Laurence, M.D.
Weill Medical College of Cornell University, New York, NY 10021
jlaurenc@med.cornell. edu 1
Stephenson J . 20 Years after AIDS emerges, HIV's complexities still loom large. JAMA 2001;285:1279-1281
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: We agree with Messori and colleagues that all relevant and available alternatives should be included and compared incrementally in a cost-effectiveness analysis and that the choice of those alternatives should be guided by clinical research.1 In our study, the efficacy of antiretroviral therapy was based on data from clinical trials, and we assessed the costs and effects of all treatments studied in each trial. For example, in our analysis of the AIDS Clinical Trials Group 320 Study, we compared triple therapy with double therapy, as well as with no therapy. As we stated, we found that double therapy was both less effective and less cost effective than triple therapy; the quantitative results of this analysis were not included because of space constraints. If triple therapy is not a viable option (e.g., because of limited resources), then double therapy would be cost effective as compared with monotherapy or no therapy. Further details are available through the National Auxiliary Publications Service. (See document no. 05582 for 6 pages of supplementary material. To order, contact National Auxiliary Publications Service, c/o Microfiche Publications, 248 Hempstead Tpke., West Hempstead, NY 11552.)
Laurence states that antiretroviral therapy extends life by only a few years. However, the analysis to which he refers focuses on patients with advanced HIV disease; gains in life expectancy with earlier treatment are greater. We also argue that a few additional years of life is a substantial clinical benefit relative to gains in life expectancy associated with other well-accepted clinical interventions. For example, gains in life expectancy associated with combination antiretroviral therapy are greater than those resulting from other widely used treatments, such as coronary-artery bypass graft surgery and treatment of both moderate hypertension and hypercholesterolemia.2
We share Laurence's concern about viral resistance and adverse effects of drugs. The effects of resistance, noncompliance, and drug toxicity were all included in our analysis. Moreover, the flexibility of the model has allowed us to evaluate specific strategies that enhance the efficacy of antiretroviral therapy, such as genotypic resistance testing and interventions to improve compliance.3,4
Finally, we agree with Laurence that effects of HIV disease are largest in low-income countries. Providing antiretroviral therapy in these settings will present formidable challenges, including linking treatment with prevention programs, developing approaches to facilitate compliance, and monitoring for drug resistance. However, as recently outlined by over 130 members of the faculty of Harvard University,5 with sufficient scientific and financial efforts to advance HIV care in low-income countries, these challenges can be overcome.
5 ReferencesKenneth A. Freedberg, M.D.
Massachusetts General Hospital, Boston, MA 02114
kfreedberg@partners.org Elena Losina, Ph.D.
Boston University School of Public Health, Boston, MA 02118Sue J. Goldie, M.D., M.P.H.
Harvard School of Public Health, Boston, MA 021151
Gold MR, Siegel JE, Russel LB, Weinstein MC. Cost-effectiveness in health and medicine. New York: Oxford University Press, 1996.
2
Wright JC ,Weinstein MC . Gains in life expectancy from medical interventions -- standardizing data on outcomes. N Engl J Med 1998;339:380-386
Full Text | Web of Science | Medline3
Weinstein MC ,Goldie SJ ,Losina E , et al. Use of genotypic resistance testing to guide HIV therapy: clinical impact and cost-effectiveness. Ann Intern Med 2001;134:440-450
Web of Science | Medline4
Goldie SJ ,Paltiel AD ,Weinstein MC , et al. Cost-effectiveness of inter ventions to improve adherence to highly-active antiretroviral therapy (HAART) in HIV-infected patients. J Gen Intern Med 2000;15:Suppl 1:117-118 abstract.
Web of Science5
Individual Members of the Faculty of Harvard University. Consensus statement on antiretroviral treatment for AIDS in poor countries. April 2001. Accessed June 15, 2001. (See http://www.cid.harvard.edu/cidinthenews/pr/consensus_aids_therapy.pdf.)
- Citing Articles (1)
Citing Articles
1
John Hornberger, J. Michael Kilby, Neil Wintfeld, Jesse Green. (2006) Cost-Effectiveness of Enfuvirtide in HIV Therapy for Treatment-Experienced Patients in the United States. AIDS Research and Human Retroviruses 22:3, 240-247
CrossRef
