PharmacoEconomics

, Volume 19, Issue 4, pp 421–436 | Cite as

Efavirenz

A Pharmacoeconomic Review of its Use in HIV Infection
  • Greg L. Plosker
  • Caroline M. Perry
  • Karen L. Goa
Adis Pharmacoeconomic Drug Evaluation

Summary

Abstract

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in the treatment of patients with HIV infection. Both US and British treatment guidelines for HIV infection recommend NNRTI- or protease inhibitor-based combinations [i.e. with nucleoside reverse transcriptase inhibitors (NRTIs)] as first-line treatment options in the management of HIV disease. Results of a pivotal randomised study (DMP 266-006) comparing efavirenz- versus indinavir-based triple combination therapy in patients with HIV infection (the majority of whom were antiretroviral therapy-naive) showed the efavirenz-based regimen was better tolerated and had greater success in achieving reductions in viral load below the limit of detection

These and other clinical data were incorporated into economic models in 2 analyses, one conducted in the US and the other in Canada. The US analysis examined long term clinical and economic outcomes predicted on the basis of response (viral load and CD4+ cell counts), tolerability and willingness to adhere to therapy. The efavirenz-based regimen was the dominant treatment strategy as it was predicted to improve survival and reduce direct medical costs in the US healthcare system. Compared with the indinavir-containing regimen, survival was increased by 11% (absolute difference) and cumulative costs were reduced by $US10 326 per patient (1998 discounted costs) at 5 years after starting treatment with efavirenz-based therapy. The Canadian analysis was conducted from the perspective of the Ontario healthcare system. This study did not consider differences in clinical efficacy between treatment groups, costs of study medication or outcomes beyond 1 year — all factors that would have favoured the efavirenz-based regimen. Of the 2 treatment options, the efavirenz-based regimen was associated with 7.4% lower average annual medical care costs, primarily because of greater costs associated with adverse clinical events with the indinavir-based regimen.

In conclusion, current treatment guidelines for HIV infection recognise efavirenz-based combination regimens as a first-line treatment option. A pivotal comparative clinical trial (DMP 266-006) showed a significantly greater virological response to efavirenz- than indinavir-based triple combination therapy, and the efavirenz-based regimen was better tolerated. These clinical data are supported by pharmacoeconomic analyses conducted in the US and Canada, both of which showed lower medical care costs with the efavirenz-based regimen. The US analysis also predicted long term health benefits, such as improved survival, with efavirenz- versus indinavir-based triple combination therapy. These results must be weighed against the inherent difficulties of predicting long term treatment failure rates from short term data, and the limited number of pharmacoeconomic analyses conducted with efavirenz to date.

Epidemiology and Cost of HIV Infection

An estimated 34.3 million individuals worldwide have HIV infection or AIDS, and estimates for the US range from 650 000 to 900 000. The disease is associated with significant morbidity, mortality and costs. In terms of average lifetime costs of direct medical care, analyses conducted in the US estimated these to be approximately $US300 000 per HIV-infected individual (1996 values). Extrapolating these data, total lifetime costs for all individuals in the US who currently have HIV infection or AIDS would reach into the hundreds of billions of dollars, and this excludes indirect costs

Costs rise markedly from early to late stages of the disease. Results of one study showed that direct costs ranged from approximately $US93 000 to $US307 000 per patient with HIV infection (year of costing not stated), depending on initial CD4+ cell counts. Along with the monetary costs, it has been estimated that, on average, each 26-year-old HIV-infected patient loses between 9.3 and 11.2 quality adjusted life-years as a result of their disease.

Clinical Profile of Efavirenz

Triple therapy with antiretroviral drug regimens including efavirenz has been shown to reduce viral load and produce immunological improvements in patients with HIV infection. Regimens comprising efavirenz (generally 600mg once daily orally) plus nucleoside reverse transcriptase inhibitors (NRTIs) and/or protease inhibitors have shown efficacy in both antiretroviral therapy—naive and—experienced adults and small numbers of children. Most randomised comparative trials were multicentre and double-blind in design.

In DMP 266-006, the largest comparative trial (which was nonblind), a triple combination of efavirenz 600mg once daily, zidovudine 300mg twice daily plus lamivudine 150mg twice daily produced more marked and durable virological responses than either indinavir 800mg every 8 hours in combination with zidovudine and lamivudine or a dual regimen of efavirenz 600mg once daily plus indinavir 1000mg every 8 hours in adults with HIV infection previously untreated with a non-nucleoside reverse transcriptase inhibitor (NNRTI), lamivudine or a protease inhibitor. Intention-to-treat analyses showed that a larger proportion of patients in the efavirenz triple therapy group than in the indinavir triple therapy group had HIV RNA levels <50 copies/ml at 48 weeks (64 vs 43%; p < 0.05) and 72 weeks (60 vs 40%; p ≤ 0.05).When the limit of detection for plasma HIV RNA levels was 400 copies/ml (primary end-point of the study), results of intention-to-treat analyses also favoured efavirenz- over indinavir-based triple combination therapy at 48 weeks (70 vs 48%; p < 0.05) and 72 weeks (67 vs 44%; p ≤ 0.05).

Efavirenz appears to be generally well tolerated. In clinical trials, dermatological effects (most notably rash) and CNS symptoms (e.g. headache, dizziness, insomnia and fatigue) were the most common adverse effects associated with efavirenz therapy. These effects were typically mild to moderate in severity and usually resolved within 2 to 3 weeks. In trial DMP 266-006, a greater proportion of patients in the indinavir-containing triple therapy group than in the efavirenz containing triple therapy group discontinued treatment because of adverse events (20.3 vs 6.5%; p < 0.001) or for any reason (43 vs 27%, p = 0.005).

Pharmacoeconomic Analyses of Efavirenz

Two pharmacoeconomic analyses have been conducted on efavirenz, 1 from the US healthcare perspective, the other from the perspective of the Ontario healthcare system in Canada. Although dissimilar in many ways, both were modeled analyses and incorporated key clinical assumptions from a randomised study (DMP 266-006) comparing efavirenz- versus indinavir-based triple combination therapy in patients with HIV infection, the majority of whom were antiretroviral therapy—naive. Importantly, if a simple analysis were undertaken considering only drug acquisition costs and short term results of DMP 266-006, efavirenz would be the dominant agent, and a more complex analysis might seem unnecessary. However, a more sophisticated analysis can explore the possibility that the cost and efficacy advantage of efavirenz versus indinavir may change over time. It also permits exploration of the sensitivity of the estimates

Results of the US analysis, which examined long term clinical and economic outcomes predicted on the basis of response (viral load and CD4+ cell counts), tolerability and willingness to adhere to therapy, showed the efavirenz-based regimen was the dominant treatment strategy in that it improved survival and reduced direct medical costs compared with the indinavir-containing regimen. Analyses were carried out for a time horizon of 5 to 15 years. At 5 years after starting treatment, the efavirenz-based regimen was associated with a cumulative discounted cost saving of $US10 326 per patient (1998 costs) and a better rate of survival (absolute difference 11%) compared with the indinavir-containing regimen. At approximately 13 years after starting medication, the cost differential disappeared and then favoured indinavir-based therapy. This result presumably reflects the survival advantage predicted for efavirenz, resulting in fewer survivors in the indinavir-based treatment group and therefore lower costs in later years. In general, results were robust to reasonable variation in key parameters in the sensitivity analysis, although increasing the indinavir response rate to 140% of the base-case value eliminated the efavirenz survival advantage within 1 year. This may be noteworthy because results of other clinical trials evaluating the efficacy of indinavir-based therapy were generally better than in the key clinical study used in the US model comparing indinavir- and efavirenz-based treatment.

Results of the Canadian analysis (published only as an abstract) also favoured the efavirenz-based regimen in economic terms, although this study did not consider outcomes beyond 1 year and assumed equivalent virological outcomes in the 2 treatment groups. Excluding study drug treatment costs, the efavirenz-based regimen was associated with 7.4% lower average annual medical care costs per patient than the indinavir-based regimen. This difference was primarily the result of higher costs for adverse clinical events with the indinavir-based regimen than with the efavirenz-based regimen (33 vs 24% of total medical care costs). Inclusion of study drug treatment costs, outcomes beyond 1 year and differences in virological response rates would have probably increased the savings associated with the efavirenz-based regimen.

References

  1. 1.
    Adkins JC, Noble S. Efavirenz. Drugs 1998 Dec; 56: 1055–64CrossRefGoogle Scholar
  2. 2.
    Moyle GJ. Efavirenz: shifting the HAART paradigm in adult HIV-1 infection. Expert Opin Invest Drug 1999 Apr; 8: 473–86CrossRefGoogle Scholar
  3. 3.
    Gazzard BG. Efavirenz in the management of HIV infection. Int J Clin Pract 1999 Jan-Feb; 53: 60–4PubMedGoogle Scholar
  4. 4.
    Fauci AS. The AIDS epidemic: considerations for the 21st century. N Engl J Med 1999; 341: 1046–50PubMedCrossRefGoogle Scholar
  5. 5.
    Report on the global HIV/AIDS epidemic - June 2000 [online]. Available from: URL: http://www.unaids.org/epidemicupdate/report/gloestim.pdf [Accessed 2000 Dec 14]
  6. 6.
    Bartlett JG, Moore R. A comprehensive plan for managed care of patients infected with human immunodeficiency virus. Clin Infect Dis 1999; 29: 50–5PubMedCrossRefGoogle Scholar
  7. 7.
    Holtgrave DR, Pinkerton SD. Updates of cost of illness and quality of life estimates for use in economic evaluations of HIV prevention programs. J Acquir Immune Defic Syndrom Hum Retrovirol 1997 Sep 1; 16: 54–62CrossRefGoogle Scholar
  8. 8.
    Moore RD. Understanding the clinical and economic outcomes of HIV therapy: the Johns Hopkins HIV Clinical Practice Cohort. J Acquir Immune Defic Syndrom Hum Retrovirol 1998; 17 Suppl. 1: S38–41CrossRefGoogle Scholar
  9. 9.
    Petrou S, Dooley M, Whitaker L, et al. The economic costs of caring for people with HIV infection and AIDS in England and Wales. Pharmacoeconomics 1996 Apr; 9: 332–40PubMedCrossRefGoogle Scholar
  10. 10.
    Bhattacharyya SK, Langley PC, Draugalis JR, et al. Lifetime costs of treating-HIV infected patients using a protease inhibitor [abstract]. J Manage Care Pharm 1999 Sep-Oct; 5: 398Google Scholar
  11. 11.
    Gill MJ, Webek M, Davidson WE. Comparative health care costs in a regional HIV/AIDS population [abstract]. 12th World AIDS Conference; 1998 Jun 28-Jul 3; Geneva: 466Google Scholar
  12. 12.
    Gebo KA, Chaisson RE, Folkemer JG, et al. Costs of HIV medical care in the era of highly active antiretroviral therapy. AIDS 1999 May 28; 13: 963–9CrossRefGoogle Scholar
  13. 13.
    Lapins D, Barrett J, Hamel EC, et al. Trends in costs of care for patients with HIV [abstract no. O-21]. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24–27; San Diego: 613Google Scholar
  14. 14.
    Pinkerton SD, Holtgrave DR. Economic impact of delaying or preventing AIDS in persons with HIV. Am J Manage Care 1999 Mar; 5: 289–98Google Scholar
  15. 15.
    Carpenter CCJ, Cooper DA, Fischl MA, et al. Antiretroviral therapy in adults: updated recommendations of the International AIDS Society - USA panel. JAMA 2000 Jan 19; 283: 381–90CrossRefGoogle Scholar
  16. 16.
    BHIVA Writing Committee, on behalf of the BHIVA Executive Committee. British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy [online].Available from: URL: http://www.aidsmap.com/bhiva/bhivagd1299.htm [Accessed 2000 Oct 31]
  17. 17.
    SUSTIVA (efavirenz capsules) Rx only. Product monograph. DuPont Pharmaceuticals Company; Feb 2000; Wilmington (DE): 1–21Google Scholar
  18. 18.
    Staszewski S, Morales-Ramirez J, Tashima KT, et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. N Engl J Med 1999 Dec 16; 341: 1865–73CrossRefGoogle Scholar
  19. 19.
    Gallant J, Seekins D, Hicks C, et al. A phase II, double-blind, placebo-control, dose-ranging study to assess the antiretroviral activity & safety of efavirenz (EFV, SUSTIVA, DMP266) in combination with open-label zidovudine (ZDV) w/ lamivudine (3TC) at >48 weeks. [DMP266–005] [abstract no. I-245]. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24–27; San Diego, 441Google Scholar
  20. 20.
    De TP, Force G, Chemlal K, et al. La Francilienne, a pilot open-label study to evaluate safety and efficacy of a potent combination therapy without protease inhibitor (3TC+ZDV+ abacavir+ efavirenz) in antiretroviral therapy naive adults: preliminary results [abstract]. 7th European Conference on Clinical Aspects and Treatment of HIV-Infection; 1999 Oct 23–27; Lisbon, 18–19Google Scholar
  21. 21.
    Cohen C, Lang J, Luskin-Hawk R, et al. Efavirenz (EFV) in combination with stavudine (D4T) and didanosine (DDI) or lamivudine (3TC) is well tolerated and efficacious in the majority of patients treated [abstract]. 7th European Conference on Clinical Aspects and Treatment of HIV-Infection; 1999 Oct 23–27; Lisbon, 15Google Scholar
  22. 22.
    Jaeger H, Gersbacher E, Wolf E, et al. Efavirenz versus nevirapine: efficacy and effects on blood lipids in PI-sparing regimens [abstract]. 13th International AIDS Conference; 2000 Jul 9; 2: 75Google Scholar
  23. 23.
    Kagan S, Jemsek J, Martin DG, et al. Initial effectiveness and tolerability of nelfinavir (NFV) in combination with efavirenz (EFV, SUSTIVA, DMP 266) in antiretroviral therapy naive or nucleoside analogue experienced HIV-1 infected patients: characterization in a phase II, open-label, multi-center study at greater than 36 weeks (Study DMP 266–024) [abstract]. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24: San Diego, 394Google Scholar
  24. 24.
    Molina JM, Ferchal F, Rancinan C, et al. A pilot study of FTC + ddI + efavirenz in treatment-naive HIV-infected adult: a potent and convenient once-a-day HAART (ANRS 091 Trial). 7th Conference on Retroviruses and Opportunistic Infections [abstract; online]. Available from: URL: http://www.retroconference.org/2000/abstracts/518.htm [Accessed 2000 Jun 7]
  25. 25.
    Knechten H, Welter U, Holmgren HC, et al. Switch from protease inhibitor containing regimens with stavudin (D4T) and lamivudin(3TC) to D4T, 3TC and efavirenz (EFV) in patients with sustained viral suppression [abstract]. 7th European Conference on Clinical Aspects and Treatment of HIV-Infection; 1999 Oct 23–27: Lisbon, 91Google Scholar
  26. 26.
    Haas DW, Fessel WJ, Delapenha RA, et al. A phase III, double-blind, placebo-controlled, multicenter study to determine the effectiveness and tolerability of the combination of efavirenz (EFV, SUSTIVA TM, DMP 266) and indinavir (IDV) versus IDV in HIV-1-infected patients receiving nucleoside analogue therapy (NRTI) at 24 weeks (study DMP 266–020) [abstract]. Clin Microbiol Infect 1999 Mar; 5 Suppl. 3: 54–5Google Scholar
  27. 27.
    Haas DW, Fessel WJ, Delapenha RA, et al. A phase II, double-blind, placebo-controlled, multi-center study to determine the effectiveness and tolerability of the combination of efavirenz (EFV, SUSTIVA, DMP 266) and indinavir (IDV) versus IDV in HIV-1 infected patients receiving nucleoside analogue (NRTI) therapy at >36 weeks. [Study DMP 266–020]. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24–27; San Diego, 441Google Scholar
  28. 28.
    Albrecht M, Katzenstein D, Bosch RJ, et al. ACTG 364: virologic efficacy of nelfinavir (NFV) and/or efavirenz (EFV) in combination with new nucleoside analogs in nucleoside experienced subjects [abstract]. 12th World AIDS Conference; 1998 Jun 28 – Jul 3; Geneva, 52Google Scholar
  29. 29.
    Albrecht M, Katzenstein D, Bosch R, et al. ACTC 364- nelfinavir (NFV) and/or efavirenz (EFV) in combination with new NRTIs in nucleoside experienced subjects (Subj): week-48 ultrasensitive (US) HIV RNA results. 7th Conference on Retroviruses and Opportunistic Infections [abstract; online]. Available from: URL: http://www.retroconference.org/2000/abstracts/531.htm [Accessed 2000 Jun 7]
  30. 30.
    Starr SE, Fletcher CV, Spector SA, et al. Combination therapy with efavirenz, nelfinavir, and nucleoside reverse-transcriptase inhibitors in children infected with human immunodeficiency virus type 1. N Engl J Med 1999 Dec 16; 341: 1874–81CrossRefGoogle Scholar
  31. 31.
    Staszewski S, Tashima K, Stryker R, et al. A phase III, multicenter, randomized, open label study to compare the antiretroviral activity and tolerability of efavirenz (EFV) + indinavir (IDV), versus EFV + zidovudine (ZDV) + lamivudine (3TC), versus IDV + ZDV + 3TC at 48 weeks (Study DMP 266006) macrolide subinhibitory concentrations [abstract]. Clin Microbiol Infect 1999 Mar; 5 Suppl. 3: 229Google Scholar
  32. 32.
    Staszewski S, Morales-Ramirez JO, Godofsky EW, et al. Longer time-to-treatment failure and durability of response with efavirenz + ZDV + 3TC: first analysis of full 1266 patient cohort from study 006 [abstract]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29: San Francisco, 473Google Scholar
  33. 33.
    Staszewski S, Nelson M, Barros Aguado C, et al. Efavirenz (EFV) + zidovudine (ZDV) + lamivudine (3TC) provides superior long-term antiretroviral activity and tolerability versus IDV + ZDV + 3TC at 72 weeks: results from a phase III, multicenter, randomized, open-label study in 450 patients (Study DPC266–006 initial cohort) [abstract]. 7th European Conference on Clinical Aspects and Treatment of HIV-Infection; 1999 Oct 23–27: Lisbon, 16Google Scholar
  34. 34.
    Levy R, Labriola D, Ruiz N. Low two year risk of virologic failure with first regimen HAART [abstract]. 8th Conference on Retroviruses and Opportunistic Infections; 2001 Feb 4–8: Chicago. In pressGoogle Scholar
  35. 35.
    Riddler S, Kahn J, Martin G, et al. Durable HIV suppression and tolerability with efavirenz (EFV) + indinavir (IDV): results at 132 weeks (Study 003-Cohort IV). 7th Conference on Retroviruses and Opportunistic Infections [online] [abstract]. Available from: URL: http://www.retroconference.org/2000/abstracts/513.htm [Accessed 2000 Jun 7]
  36. 36.
    Ruiz N, Manion D, Riddler S, et al. Durable clinical anti-HIV-1 activity at 84 weeks and tolerability for efavirenz (EFZ) in combination with indinavir (IDV) [study DMP 266–003, cohort IV] [abstract no. P75]. AIDS 1998 Nov; 12 Suppl. 4: S36Google Scholar
  37. 37.
    Römer K, Fatkenheuer G, Bethe U, et al. Salvage therapy with efavirenz [abstract]. 7th European Conference on Clinical Aspects and Treatment of HIV-Infection; 1999 Oct 23–27: Lisbon, 112Google Scholar
  38. 38.
    Masur H, Falloon J, Thomas D, et al. Durability of abacavir/amprenavir/efavirenz combination salvage therapy - preliminary 48-week response (CNA2007) [abstract]. 7th European Conference on Clinical Aspects and Treatment of HIV-Infection; 1999 Oct 23–27: Lisbon, 281Google Scholar
  39. 39.
    Testa L, Suter F, Maggiolo F, et al. Salvage therapy with non nucleoside reverse transcriptase inhibitors (NNRTI) in patients failing protease inhibitors containing regimens [abstract]. AIDS 1998 Nov; 12 Suppl. 4: S49Google Scholar
  40. 40.
    Farthing C, Sampson M, Somero M, et al. Effectiveness of adefovir+abacavir+efavirenz as salvage therapy for patients with documented virologic failure to other combination antiretroviral drug regimens [abstract]. Clin Infect Dis 1998 Oct; 27: 1004Google Scholar
  41. 41.
    Falloon J, Masur H, Brosgart C, et al. Salvage therapy with abacavir, amprenavir, and efavirenz in subjects with plasma HIV-1 RNA > 500 copies /mL despite protease inhibitor (PI) therapy [abstract]. Clin Infect Dis 1998 Oct; 27: 1004Google Scholar
  42. 42.
    Shulman N, Zolopa A, Passaro DJ, et al. Efavirenz and adefovir dipivoxil-based salvage in highly treatment-experienced patients: clinical and genotypic predictors of virologic response. J Acquir Immune Defic Syndr 2000; 23: 221–6PubMedGoogle Scholar
  43. 43.
    Wasmuth J-C, Römer K, Salzberger B, et al. Efficacy and safety of abacavir+efavirenz plus background combination therapy as a salvage regimen in HIV-infected individuals [abstract]. 7th European Conference on Clinical Aspects and Treatment of HIV-Infection; 1999 Oct 23–27: Lisbon, 15Google Scholar
  44. 44.
    Seminari E, Maggiolo F, Villani P, et al. Efavirenz, nelfinavir, and stavudine rescue combination therapy in HIV-1-positive patients heavily pretreated with nucleoside analogues and protease inhibitors. J Acquir Immune Defic Syndr 1999 Dec 15; 22: 453–60Google Scholar
  45. 45.
    Gilson I, Busalacchi M. Abacavir/efavirenz/adefovir salvage regimen for refractory HIV disease [abstract]. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24; San Diego, 428Google Scholar
  46. 46.
    Antela A, Moreno A, Hertogs K, et al. Different efficacy of efavirenz-containing rescue regimens for patients failing protease inhibitors depending on previous nevirapine experience [abstract no. 514]. Seventh European Conference on Clinical Aspects and Treatment of HIV-Infection; 1999 Oct 23–27; Lisbon, 106–7Google Scholar
  47. 47.
    Hammer S, Mellors J, Vaida F, et al. A randomized, placebo-controlled trial of saquinavir (SQV)sgc, indinavir (IDV) or nelfinavir (NFV) in combination with amprenavir (APV), abacavir (ABC), efavirenz (EFZ) and adefovir (ADV) in patients (Pts) with protease inhibitor (PI) failure. 7th Conference on Retroviruses and Opportunistic Infections; 2000 Jan 30 – Feb 2; San FranciscoGoogle Scholar
  48. 48.
    Ruiz NM, Manion DJ, Cain VA, et al. Potential adverse experiences associated with efavirenz [abstract]. Clin Infect Dis 1998 Oct; 27: 1013Google Scholar
  49. 49.
    Temesgen Z, Wright AJ. Antiretrovirals. Mayo Clin Proc 1999; 74: 1284–301PubMedCrossRefGoogle Scholar
  50. 50.
    Caro JJ, O’Brien JA, Migliaccio-Walle K, et al. Economic analysis of initial HIV treatment: efavirenz- versus indinavir-containing triple therapy. Pharmacoeconomics 2001; 19 (1): 95–104PubMedCrossRefGoogle Scholar
  51. 51.
    Williams G, Palmer R, McMurchy D, et al. Cost comparison of efavirenz (EFV) and indinavir (IDV) combination therapies for HIV infection [abstract]. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1999 Sep 26–29: San Francisco, 736Google Scholar
  52. 52.
    Hammer SM, Squires KE, Hughes MD, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. N Engl J Med 1997; 337: 725–33PubMedCrossRefGoogle Scholar
  53. 53.
    Gazzard B, AVANTI 2. A randomised double blind, comparative trial to evaluate the efficacy, safety and tolerance of AZT/3TC vs. AZT/3TC/indinavir in anti-retroviral naive patients: 100 week data. AIDS 1998; 12 Suppl. 4: S35Google Scholar
  54. 54.
    Mellors JW, Muñoz A, Giorgi JV, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers forHIV-1 infection. Ann Intern Med 1997; 126: 946–54PubMedGoogle Scholar
  55. 55.
    Yerly S, Perneger TV, Hirschel B, et al. A critical assessment of the prognostic value of HIV-1 RNA levels and CD4+ cell counts in HIV-infected patients. Arch Intern Med 1998; 158: 247–52PubMedCrossRefGoogle Scholar
  56. 56.
    Katzenstein DA, Hammer SM, Hughes MD, et al. The relation of virologic and immunologic markers to clinical outcomes after nucleoside therapy in HIV-infected adults with 200 to 500 CD4 cells per cubic millimeter. N Engl J Med 1996; 335: 1091–8PubMedCrossRefGoogle Scholar
  57. 57.
    Plosker GL, Noble S. Indinavir: a review of its use in the management of HIV infection. Drugs 1999 Dec; 58 (6): 1165–203PubMedCrossRefGoogle Scholar
  58. 58.
    Clumeck N. Choosing the best initial therapy for HIV-1 infection. N Engl J Med 1999 Dec 16; 341 (25): 1925–6PubMedCrossRefGoogle Scholar
  59. 59.
    Rogers PA, Gore SM, Whitmore-Overton SE, et al. United Kingdom AIDS survival in adults. AIDS 1996; 10: 1571–8PubMedCrossRefGoogle Scholar
  60. 60.
    Palella Jr FJ, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998; 338: 853–60PubMedCrossRefGoogle Scholar
  61. 61.
    Egger M, Hirschel B, Francioli P, et al. Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study. Swiss HIV Corhort Study. BMJ 1997; 315: 1194–9PubMedCrossRefGoogle Scholar
  62. 62.
    Mocroft A, Vella S, Benfield TL, et al. Changing patterns of mortality across Europe in patients infected with HIV-1. Lancet 1998; 352: 1725–30PubMedCrossRefGoogle Scholar
  63. 63.
    Elliott EB. Hope for HIV patients: news from the 12th International Conference on HIV and AIDS [news]. Can Fam Physician 1999 Mar; 45: 829–31PubMedGoogle Scholar
  64. 64.
    Hogg RS, Yip B, Kully C, et al. Improved survival among HIV infected patients after initiation of triple-drug antiretroviral regimens. Can Med Assoc J 1999; 160 (5): 659–65Google Scholar
  65. 65.
    Mole L, Ockrim K, Holodniy M. Decreased medical expenditures for care of HIV-seropositive patients: the impact of highly active antiretroviral therapy at a US Veterans Affairs Medical Center. Pharmacoeconomics 1999 Sep; 16: 307–15PubMedCrossRefGoogle Scholar
  66. 66.
    Vittinghoff E, Scheer S, O’Malley P, et al. Combination antiretroviral therapy and recent declines in AIDS incidence and mortality. J Infect Dis 1999; 179: 717–20PubMedCrossRefGoogle Scholar
  67. 67.
    Rachlis AR, Palmer RWH, Doswell M. Improved survival time and CD4 slope associated with recent advances in HIV antiretroviral therapy [abstract no. 194]. 5th Conference on Retrovirus and Opportunistic Infections; 1998 Feb 1–5; ChicagoGoogle Scholar
  68. 68.
    Anis AH, Hogg RS, Wang X-h, et al. Modelling the potential economic impact of viral load-driven triple drug combination antiretroviral therapy. Pharmacoeconomics 1998 Jun; 13: 697–705PubMedCrossRefGoogle Scholar
  69. 69.
    McCollum M, Klaus B, La Rue R, et al. HAART reduced overall costs of HIV care at DVAMC-Denver [abstract no. 200/ Session 28]. 5th Conference on Retrovirus and Opportunistic Infections; 1998 Feb 1–5; ChicagoGoogle Scholar
  70. 70.
    Melnick D, Greiner D, Little P, et al. Impact of aggressive management of HIV infection on clinical outcome and cost of care within a health maintenance organization [abstract no. 201/ Session 28]. 5th Conference on Retrovirus and Opportunistic Infections; 1998 Feb 1–5; ChicagoGoogle Scholar
  71. 71.
    Domingo P, Guardiola JM, Ris J, et al. The impact of new antiretroviral regimes on HIV-associated hospital admissions and deaths. AIDS 1998; 12: 529–43PubMedGoogle Scholar
  72. 72.
    Mouton Y, Alfandari S, Valette M, et al. Impact of protease inhibitors on AIDS-defining events and hospitalizations in 10 French AIDS reference centres. AIDS 1997 Oct; 11: F101–5CrossRefGoogle Scholar
  73. 73.
    Pehrson P, Hejdeman B, Lidman K. New principals for treatment — how does it affect the costs for HIV care? [abstract no. 60546]. 12th World AIDS Conference; 1998 Jul; GenevaGoogle Scholar
  74. 74.
    Ruane PJ, Tam JT, Zakowski PC, et al. Recent advances in antiviral therapy (ARV) for HIVcan result in lower total costs - 3 year analysis [abstract no. 24136]. 12th World AIDS Conference; 1998 Jul; GenevaGoogle Scholar
  75. 75.
    Stansell JD, Daly D, Hamel E, et al. Economic impact of protease inhibitors on HIV treatment [abstract]. J Manage Care Pharm 1999 Sep-Oct; 5: 406Google Scholar
  76. 76.
    Shinohara YT, Wallace MR, Tasker SA, et al. The changing economics of HIV care [abstract]. Clin Infect Dis 1998 Oct; 27: 1046Google Scholar
  77. 77.
    Urdaneta ME, Markson LE, Barrett J, et al. Economic impact of HIV care in a managed care environment [abstract]. J Manage Care Pharm 1999; 5 (3): 202Google Scholar
  78. 78.
    Sendi PP, Bucher HC, Harr T, et al. Cost effectiveness of highly active antiretroviral therapy in HIV-infected patients. AIDS 1999 Jun 18; 13: 1115–22CrossRefGoogle Scholar
  79. 79.
    Gazzard B, Moyle G, on behalf of the BHIVA Guidelines Writing Committee. 1998 revision to the British HIV Association guidelines for antiretroviral treatment of HIV seropositive individuals. Lancet 1998; 352: 314–6PubMedCrossRefGoogle Scholar
  80. 80.
    Youle M, Trueman P, Simpson K. Health economics in HIV disease: a review of the European literature. Pharmacoeconomics 1999; 15 Suppl. 1: 1–12PubMedCrossRefGoogle Scholar
  81. 81.
    Johannesson M, Jonsson B, Kjekshus J, et al. Cost effectiveness of simvastatin treatment to lower cholesterol levels in patients with coronary heart disease. Scandinavian Simvastatin Survival Study Group. N Engl J Med 1997; 336: 332–6PubMedCrossRefGoogle Scholar
  82. 82.
    Schulman KA, Lynn LA, Glick HA, et al. Cost effectiveness of low-dose zidovudine therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection. Ann Intern Med 1991; 114: 798–802PubMedGoogle Scholar
  83. 83.
    Fumaz CR, Tuldrà A, Ferrer MJ, et al. Assessment of quality of life, adherence and emotional status in patients treated with efavirenz [abstract]. 7th European Conference on Clinical Aspects and Treatment of HIV-Infection (Late Breakers); 1999 Oct 23–27; Lisbon, 4Google Scholar

Copyright information

© Adis International Limited 2001

Authors and Affiliations

  • Greg L. Plosker
    • 1
  • Caroline M. Perry
    • 1
  • Karen L. Goa
    • 1
  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

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