Skip to main content
Erschienen in: PharmacoEconomics 5/2000

01.11.2000 | Review Article

HIV-1 Drug Resistance Genotyping

A Review of Clinical and Economic Issues

verfasst von: Carine Chaix-Couturier, Christopher Holtzer, Kathryn A. Phillips, Professor Isabelle Durand-Zaleski, John Stansell

Erschienen in: PharmacoEconomics | Ausgabe 5/2000

Einloggen, um Zugang zu erhalten

Abstract

The development of mutations associated with resistance to antiretroviral therapy (ART) has been shown to be a major cause of treatment failure in patients infected with HIV-1. These resistance mutations can be assessed by a genotyping test that probes for specific mutations within the HIV genome or sequences specific genes, at a cost $US500/test (2000 prices). The stated goal of HIV-1 genotyping is to target HIV therapy effectively. This, as shown in the preliminary research, should result in better clinical outcomes and a lower incidence of virological failure and may be associated with lower costs of treatment. Failure of ART may result in an increase in costs of at least $US250 per patient per month, as assessed in 1 study, with costs rising further as patients experience multiple virological failures. Therefore, there is an economic as well as a therapeutic premium on the prevention of ART failure.
The actual economic cost of genotyping has been preliminarily explored in the context of the antiretro VIRal ADAPTation (VIRADAPT) trial, which found no significant difference in the 1-year treatment cost of patients with and without genotyping. There is some evidence of cost neutrality or savings with genotypic testing but it needs to be further explored within the context of carefully framed prospective trials.
Literatur
1.
Zurück zum Zitat Deeks S, Loftus R, Cohen P, et al. Incidence and predictors of virologic failure to indinavir and/or ritonavir in an urban health clinic [abstract no. LB-2]. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): 1997 Sep 28-Oct 1, Toronto (ON) Deeks S, Loftus R, Cohen P, et al. Incidence and predictors of virologic failure to indinavir and/or ritonavir in an urban health clinic [abstract no. LB-2]. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): 1997 Sep 28-Oct 1, Toronto (ON)
2.
Zurück zum Zitat Deeks S, Hecht FM, Swanson M, et al. HIV RNA and CD4 cell count response to protease inhibitor therapy in an urban AIDS clinic: response to both initial and salvage therapy. AIDS 1999; 13: F35–44CrossRef Deeks S, Hecht FM, Swanson M, et al. HIV RNA and CD4 cell count response to protease inhibitor therapy in an urban AIDS clinic: response to both initial and salvage therapy. AIDS 1999; 13: F35–44CrossRef
3.
Zurück zum Zitat Fatkenheuer G, Theisen A, Rockstroh J, et al. Virologic treatment failure of protease inhibitor therapy in an unselected cohort of HIV patients. AIDS 1997; 11: F113–6CrossRef Fatkenheuer G, Theisen A, Rockstroh J, et al. Virologic treatment failure of protease inhibitor therapy in an unselected cohort of HIV patients. AIDS 1997; 11: F113–6CrossRef
4.
Zurück zum Zitat Drake JW. Rates of spontaneous mutations among RNA viruses. Proc Natl Acad Sci U S A 1993; 90: 4171–5PubMedCrossRef Drake JW. Rates of spontaneous mutations among RNA viruses. Proc Natl Acad Sci U S A 1993; 90: 4171–5PubMedCrossRef
5.
Zurück zum Zitat Ho D, Neuman AU, Perelson AS. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 1995; 373: 123–6PubMedCrossRef Ho D, Neuman AU, Perelson AS. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 1995; 373: 123–6PubMedCrossRef
6.
Zurück zum Zitat Perelson AS, EssunNeumann AU, Markowitz M, et al. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 1996; 271: 1582–6PubMedCrossRef Perelson AS, EssunNeumann AU, Markowitz M, et al. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 1996; 271: 1582–6PubMedCrossRef
7.
Zurück zum Zitat Perrin L, Telenti A. HIV treatment failure: testing for HIV resistance in clinical practice. Science 1998; 280: 1871–3PubMedCrossRef Perrin L, Telenti A. HIV treatment failure: testing for HIV resistance in clinical practice. Science 1998; 280: 1871–3PubMedCrossRef
8.
Zurück zum Zitat Durant J, Clevenbergh P, Halfon P, et al. Drug-resistance genotyping in HIV-1 therapy: the VIRADAPT randomised controlled trial. Lancet 1999; 353: 2195–9PubMedCrossRef Durant J, Clevenbergh P, Halfon P, et al. Drug-resistance genotyping in HIV-1 therapy: the VIRADAPT randomised controlled trial. Lancet 1999; 353: 2195–9PubMedCrossRef
9.
Zurück zum Zitat Baxter JD, Mayers DL, Wentworth DN, et al. A pilot study of the Short-term effects of antiretroviral management based on plasma genotypic antiretroviral resistance testing (GART) in patients failing antiretroviral therapy [abstract no. LB8]. In: 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jan 31–Feb 4; Chicago (IL) Baxter JD, Mayers DL, Wentworth DN, et al. A pilot study of the Short-term effects of antiretroviral management based on plasma genotypic antiretroviral resistance testing (GART) in patients failing antiretroviral therapy [abstract no. LB8]. In: 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jan 31–Feb 4; Chicago (IL)
10.
Zurück zum Zitat Melnick D, Rosenthal DL, Cameron M, et al. Impact of phenotypic antiretroviral drug resistance testing on the response to salvage antiretroviral therapy (ART) in heavily experienced patients [abstract no. 786]. Presented at: 7th Conference on Retroviruses and Opportunistic Infections; 2000 Feb; San Francisco (CA) Melnick D, Rosenthal DL, Cameron M, et al. Impact of phenotypic antiretroviral drug resistance testing on the response to salvage antiretroviral therapy (ART) in heavily experienced patients [abstract no. 786]. Presented at: 7th Conference on Retroviruses and Opportunistic Infections; 2000 Feb; San Francisco (CA)
11.
Zurück zum Zitat Cohen C, Hunt S, Sension M, et al. Phenotypic resistance testing significantly improves response to therapy (Tx): a randomized trial (VIRA 3001) [abstract no. 237]. Presented at: 7th Conference on Retroviruses and Opportunistic Infections; 2000 Feb; San Francisco (CA) Cohen C, Hunt S, Sension M, et al. Phenotypic resistance testing significantly improves response to therapy (Tx): a randomized trial (VIRA 3001) [abstract no. 237]. Presented at: 7th Conference on Retroviruses and Opportunistic Infections; 2000 Feb; San Francisco (CA)
12.
Zurück zum Zitat Clevenbergh P, Durant J, Halfon P. Persisting long-term benefit of genotypic-guided treatment of HIV-infected patients failing HAART. The Viradapt study: week 48 follow-up. Antiviral Ther 2000; 5: 65–70 Clevenbergh P, Durant J, Halfon P. Persisting long-term benefit of genotypic-guided treatment of HIV-infected patients failing HAART. The Viradapt study: week 48 follow-up. Antiviral Ther 2000; 5: 65–70
13.
Zurück zum Zitat Chaix C, Grenier-Sennelier C, Durant J, et al. Economic Evaluation of drug resistance genotyping for the adaptation of treatment in HIV-infected patients in the VIRADAPT study. J Acquir Immune Defic Syndr 2000; 24 (3): 227–31PubMed Chaix C, Grenier-Sennelier C, Durant J, et al. Economic Evaluation of drug resistance genotyping for the adaptation of treatment in HIV-infected patients in the VIRADAPT study. J Acquir Immune Defic Syndr 2000; 24 (3): 227–31PubMed
14.
Zurück zum Zitat Hirsch MS, Brun-Vizinet F, D’Aquila RT. Antiretroviral drug resistance testing in adult HIV-1 infection - recommendations of an International AIDS Society - USA Panel. JAMA 2000; 283: 2417–26PubMedCrossRef Hirsch MS, Brun-Vizinet F, D’Aquila RT. Antiretroviral drug resistance testing in adult HIV-1 infection - recommendations of an International AIDS Society - USA Panel. JAMA 2000; 283: 2417–26PubMedCrossRef
15.
Zurück zum Zitat Donovan R, Berrey M, Corey L, et al. Prevalence of protease inhibitor and reverse transcriptase inhibitor resistance mutations in recent HIV-1 seroconverters in Seattle [abstract no. 217]. In: 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jan 31–Feb 4; Chicago (IL) Donovan R, Berrey M, Corey L, et al. Prevalence of protease inhibitor and reverse transcriptase inhibitor resistance mutations in recent HIV-1 seroconverters in Seattle [abstract no. 217]. In: 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jan 31–Feb 4; Chicago (IL)
16.
Zurück zum Zitat Hecht FM, Grant RM, Petropoulos CJ. Sexual transmission of an HIV-1 variant resistant to multiple reverse-transcriptase and protease inhibitors. N Engl J Med 1998; 339: 307–11PubMedCrossRef Hecht FM, Grant RM, Petropoulos CJ. Sexual transmission of an HIV-1 variant resistant to multiple reverse-transcriptase and protease inhibitors. N Engl J Med 1998; 339: 307–11PubMedCrossRef
17.
Zurück zum Zitat Precious H, Leigh-Brown AJ, Gunthard HF. A multiple regression model predicting response to combination therapy from baseline sequence data identifies amino acid sites not previously associated with resistance [abstract no. 14]. In: 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jan 31–Feb 4; Chicago (IL) Precious H, Leigh-Brown AJ, Gunthard HF. A multiple regression model predicting response to combination therapy from baseline sequence data identifies amino acid sites not previously associated with resistance [abstract no. 14]. In: 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jan 31–Feb 4; Chicago (IL)
18.
Zurück zum Zitat Holder DJ, Condra JC, Schleif WA, et al. Virologic failure during combination therapy with Crixivan and RT inhibitors is often associated with expression of resistance-associated mutations in RT only [abstract no. 491]. In: 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jan 31–Feb 4; Chicago (IL) Holder DJ, Condra JC, Schleif WA, et al. Virologic failure during combination therapy with Crixivan and RT inhibitors is often associated with expression of resistance-associated mutations in RT only [abstract no. 491]. In: 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jan 31–Feb 4; Chicago (IL)
19.
Zurück zum Zitat Montoya JG, Schapiro JM, Zolopa AR, et al. Treatment of patients (pts.) who have virus with mutations suggesting panprotease and -reverse transcriptase drug resistance [abstract no. 135]. In: 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jan 31–Feb 4; Chicago (IL) Montoya JG, Schapiro JM, Zolopa AR, et al. Treatment of patients (pts.) who have virus with mutations suggesting panprotease and -reverse transcriptase drug resistance [abstract no. 135]. In: 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jan 31–Feb 4; Chicago (IL)
20.
Zurück zum Zitat Lorenzi P, Opravil M, Hirschel B. Resistance mutations as predictor of response to salvage therapy [abstract no. 140]. In: 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jan 31–Feb 4; Chicago (IL) Lorenzi P, Opravil M, Hirschel B. Resistance mutations as predictor of response to salvage therapy [abstract no. 140]. In: 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jan 31–Feb 4; Chicago (IL)
21.
Zurück zum Zitat Bozzette SA, Berry SH, Duan N, et al. The care of HIV-infected adults in the United States. HIV cost and services utilization study consortium. N Engl J Med 1998; 339 (26): 1897–904PubMedCrossRef Bozzette SA, Berry SH, Duan N, et al. The care of HIV-infected adults in the United States. HIV cost and services utilization study consortium. N Engl J Med 1998; 339 (26): 1897–904PubMedCrossRef
22.
Zurück zum Zitat Beck EJ, Tolley K, Power A, et al. The use and cost of HIV service provision in England in 1996. National Prospective Monitoring System (NPMS) Steering Group and NPMS Working Party on Costs. Pharmacoeconomics 1998; 14: 639–52PubMedCrossRef Beck EJ, Tolley K, Power A, et al. The use and cost of HIV service provision in England in 1996. National Prospective Monitoring System (NPMS) Steering Group and NPMS Working Party on Costs. Pharmacoeconomics 1998; 14: 639–52PubMedCrossRef
23.
Zurück zum Zitat Perdue BE, Weidle PJ, Everson-Mays RE, et al. Evaluating the cost of medications for ambulatory HIV-infected persons in association with landmark changes in antiretroviral therapy. J Acquir Immune Defic Syndr Human Retrovirol 1998; 17: 354–60CrossRef Perdue BE, Weidle PJ, Everson-Mays RE, et al. Evaluating the cost of medications for ambulatory HIV-infected persons in association with landmark changes in antiretroviral therapy. J Acquir Immune Defic Syndr Human Retrovirol 1998; 17: 354–60CrossRef
24.
Zurück zum Zitat Anis AH, Hogg RS, Yip B, et al. Average annual drug cost and its determinants in a population based cohort of HIV-positive adult men and women. Pharmacoeconomics 1999; 13: 327–36CrossRef Anis AH, Hogg RS, Yip B, et al. Average annual drug cost and its determinants in a population based cohort of HIV-positive adult men and women. Pharmacoeconomics 1999; 13: 327–36CrossRef
25.
Zurück zum Zitat Shapiro MF, Morton SC, McCaffrey DF, et al. Variations in the care of HIV-infected adults in the United States. JAMA1999; 281: 2305–15PubMedCrossRef Shapiro MF, Morton SC, McCaffrey DF, et al. Variations in the care of HIV-infected adults in the United States. JAMA1999; 281: 2305–15PubMedCrossRef
26.
Zurück zum Zitat Palella Jr FJ, Delaney KM, Moorman AC. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998; 338: 853–60PubMedCrossRef Palella Jr FJ, Delaney KM, Moorman AC. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998; 338: 853–60PubMedCrossRef
27.
Zurück zum Zitat Holtzer CD, Jacobson MA, Hadley WK. Decline in the rate of specific opportunistic infections at the San Francisco General Hospital: 1994–1997 [letter]. AIDS 1998; 12: 1931–2PubMed Holtzer CD, Jacobson MA, Hadley WK. Decline in the rate of specific opportunistic infections at the San Francisco General Hospital: 1994–1997 [letter]. AIDS 1998; 12: 1931–2PubMed
28.
Zurück zum Zitat Brettle RP, Wilson A, Povey S. Combination therapy for HIV: the effect on inpatient activity, morbidity and mortality of a cohort of patients. Int J Std Aids 1998; 9: 80–7PubMedCrossRef Brettle RP, Wilson A, Povey S. Combination therapy for HIV: the effect on inpatient activity, morbidity and mortality of a cohort of patients. Int J Std Aids 1998; 9: 80–7PubMedCrossRef
29.
Zurück zum Zitat Lapins D, Barrett J, Hamel E, et al. Trends in costs of care for patients with HIV[abstract]. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 1998 Sep 26–30; San Diego (CA) Lapins D, Barrett J, Hamel E, et al. Trends in costs of care for patients with HIV[abstract]. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 1998 Sep 26–30; San Diego (CA)
30.
Zurück zum Zitat Rabeneck L, Menke T, Wray N. How good are US studies of HIV costs of care? Med Care 1999; 37: 748–59PubMedCrossRef Rabeneck L, Menke T, Wray N. How good are US studies of HIV costs of care? Med Care 1999; 37: 748–59PubMedCrossRef
31.
Zurück zum Zitat Pinkerton SD, Holtgrave DR. Economic impact of delaying or preventing AIDS in persons with HIV. Am J Manage Care 1999; 3: 289–98 Pinkerton SD, Holtgrave DR. Economic impact of delaying or preventing AIDS in persons with HIV. Am J Manage Care 1999; 3: 289–98
32.
Zurück zum Zitat Moore RD, Gebo K, Barlett JG, et al. Health care costs for 1995–1998 in AIDS [abstract no. 102]. In: 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jan 31–Feb 4; Chicago (IL) Moore RD, Gebo K, Barlett JG, et al. Health care costs for 1995–1998 in AIDS [abstract no. 102]. In: 6th Conference on Retroviruses and Opportunistic Infections; 1999 Jan 31–Feb 4; Chicago (IL)
33.
Zurück zum Zitat Holtzer C, Deeks SG. Impact of HIV-1 protease inhibitors on the cost of treating HIV/AIDS patients. Drug Benefit Trends 1998; 10: 27–31 Holtzer C, Deeks SG. Impact of HIV-1 protease inhibitors on the cost of treating HIV/AIDS patients. Drug Benefit Trends 1998; 10: 27–31
34.
Zurück zum Zitat Stansell J, Barrett J, Holtzer C, et al. Incremental costs of HIV suppression in HIV therapeutic failure. In: 7th Conference on retroviruses and opportunistic infections; 2000 Jan 30–Feb 03; San Francisco (CA) Stansell J, Barrett J, Holtzer C, et al. Incremental costs of HIV suppression in HIV therapeutic failure. In: 7th Conference on retroviruses and opportunistic infections; 2000 Jan 30–Feb 03; San Francisco (CA)
35.
Zurück zum Zitat Mole L, Ockrim K, Holodniy M. Decrease medical expenditures for care of HIV-seropositive patients. Pharmacoeconomics 1999; 16 (3): 307–15PubMedCrossRef Mole L, Ockrim K, Holodniy M. Decrease medical expenditures for care of HIV-seropositive patients. Pharmacoeconomics 1999; 16 (3): 307–15PubMedCrossRef
36.
Zurück zum Zitat Anis AH, Wang X, Harrigan R, et al. The cost-effectiveness of immediate ritonavir-saquinavir therapy versus reistance testing and a drug holiday in HIV patients failing protease inclusive regimens [abstract]. Med Decision Making. Reno (NV): Society for Medical Decision Making, 1999 Oct 3–6 Anis AH, Wang X, Harrigan R, et al. The cost-effectiveness of immediate ritonavir-saquinavir therapy versus reistance testing and a drug holiday in HIV patients failing protease inclusive regimens [abstract]. Med Decision Making. Reno (NV): Society for Medical Decision Making, 1999 Oct 3–6
37.
Zurück zum Zitat Anis AH, Wang X, Harrigan R, et al. Optimizing drug treatment: a cost-effectiveness analysis of HIV/AIDS drug resistance testing [abstract]. Med Decision Making. Reno (NV): Society for Medical Decision Making, 1999 Oct 3–6 Anis AH, Wang X, Harrigan R, et al. Optimizing drug treatment: a cost-effectiveness analysis of HIV/AIDS drug resistance testing [abstract]. Med Decision Making. Reno (NV): Society for Medical Decision Making, 1999 Oct 3–6
38.
Zurück zum Zitat Weinstein MC, Goldie SJ, Cohen C, et al. Resistance testing to guide the choice of second-line antiretroviral therapy in HIV: clinical impact and cost-effectiveness [abstract]. Med Decision Making. Reno (NV): Society for Medical Decision Making, 1999 Oct Weinstein MC, Goldie SJ, Cohen C, et al. Resistance testing to guide the choice of second-line antiretroviral therapy in HIV: clinical impact and cost-effectiveness [abstract]. Med Decision Making. Reno (NV): Society for Medical Decision Making, 1999 Oct
39.
Zurück zum Zitat Gold M, Siegel J, Russell L, et al. Cost-effectiveness in health and medicine. New York: Oxford University Press, 1996 Gold M, Siegel J, Russell L, et al. Cost-effectiveness in health and medicine. New York: Oxford University Press, 1996
40.
Zurück zum Zitat Hall J, Viney R, Haas M. Taking a count: the evaluation of genetic testing. Aust N Z J Public Health 1998; 22: 754–8PubMedCrossRef Hall J, Viney R, Haas M. Taking a count: the evaluation of genetic testing. Aust N Z J Public Health 1998; 22: 754–8PubMedCrossRef
41.
Zurück zum Zitat Grann V, Whang W, Jacobson J, et al. Benefits and costs of screening Ashkenazi Jewishwomen for BRCA1 and BRCA2. J Clin Oncol 1999; 17: 494–500PubMed Grann V, Whang W, Jacobson J, et al. Benefits and costs of screening Ashkenazi Jewishwomen for BRCA1 and BRCA2. J Clin Oncol 1999; 17: 494–500PubMed
42.
Zurück zum Zitat Sadee W. Genomics and drugs: finding the optimal drug for the right patient. Pharmaceut Res 1998; 15: 959–36CrossRef Sadee W. Genomics and drugs: finding the optimal drug for the right patient. Pharmaceut Res 1998; 15: 959–36CrossRef
43.
Zurück zum Zitat Phillips K, Holtgrave D. Using cost-effectiveness/cost-benefit analysis to allocate health resources: a level playing field for prevention? Am J Prev Med 1997; 13: 18–25PubMed Phillips K, Holtgrave D. Using cost-effectiveness/cost-benefit analysis to allocate health resources: a level playing field for prevention? Am J Prev Med 1997; 13: 18–25PubMed
Metadaten
Titel
HIV-1 Drug Resistance Genotyping
A Review of Clinical and Economic Issues
verfasst von
Carine Chaix-Couturier
Christopher Holtzer
Kathryn A. Phillips
Professor Isabelle Durand-Zaleski
John Stansell
Publikationsdatum
01.11.2000
Verlag
Springer International Publishing
Erschienen in
PharmacoEconomics / Ausgabe 5/2000
Print ISSN: 1170-7690
Elektronische ISSN: 1179-2027
DOI
https://doi.org/10.2165/00019053-200018050-00002

Weitere Artikel der Ausgabe 5/2000

PharmacoEconomics 5/2000 Zur Ausgabe