Cost-efficacy comparison among three antiretroviral regimens in HIV-1 infected, treatment-experienced patients.

BACKGROUND AND OBJECTIVE: In the face of increasing antiretroviral (ARV) treatment options and costs, payers are progressively challenged with prioritising resources. The cost effectiveness of the ARV agent enfuvirtide has been shown to be comparable to that of other available HIV treatment strategies, based on Markov modeling. However, an evaluation of enfuvirtide treatment costs that considers the impact of virological and immunological responses to therapy may provide a more clinically meaningful perspective for primary HIV healthcare providers. The aim of this study was to assess the cost per unit change in efficacy (HIV RNA decreases and CD4 count increases) of three different ARV regimens for triple class-experienced HIV-1 infected patients using actual drug costs and data from randomised, controlled clinical trials. STUDY DESIGN: The analysis included three steps. First, re-analysis of 48-week clinical trial data (T-20 vs Optimized Regimen Only [TORO]) to allow for a more direct comparison of enfuvirtide versus other commonly used ARV agents. All patients included in the re-analysis received a common optimised background (COB) regimen of three drugs: two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and a ritonavir-boosted protease inhibitor (PI), lopinavir. HIV RNA levels and CD4 count changes were determined for three patient groups according to the treatment received - group 1: COB + enfuvirtide; group 2: COB + PI; group 3: COB + NRTI + PI. The second step of the analysis involved calculating the annualised regimen costs ($US wholesaler acquisition cost) for each patient group. In the third step, cost-efficacy ratios were calculated and compared between groups: (a) the annualised regimen cost ($US)/change in viral load from baseline, and (b) the annualised regimen cost ($US)/change in CD4+ cell count from baseline. RESULTS: One hundred and fifty-seven patients were included in this previously unplanned secondary analysis (group 1: 79 patients; group 2: 42 patients; group 3: 36 patients). HIV RNA and CD4 count changes from baseline to week 48 were -1.80, -0.89 and -0.61 log(10) copies/mL (p < 0.001 for enfuvirtide vs each non-enfuvirtide group) and +102, +57 and +52 cells/mm(3) (p < 0.05 for enfuvirtide versus each non-enfuvirtide subgroup) for groups 1, 2 and 3, respectively. The annualised costs of the combination therapies were $US 35,624, $US 27,549 and $US 30,624; and the costs per 0.50 log(10) copies/mL HIV RNA decrease were $US 9,872, $US 15,542 and $US 24,907 (p < 0.05 for enfuvirtide vs each non-enfuvirtide subgroup) for groups 1, 2 and 3, respectively. The costs per 25 cells/mm(3) CD4 count increase were $US 8,722, $US 12,127 and $US 14,636 for subgroups 1, 2 and 3, respectively. Similar patterns in regimen cost per unit change were achieved after adjusting for baseline prognostic variables. The incremental cost-efficacy ratios for group 1 versus the combination of groups 2 and 3 were $US 3,124 for HIV RNA reduction and $US 3,239 for CD4 count increase. CONCLUSION: Enfuvirtide-containing regimens are associated with higher cost as well as improved virological and immunological outcomes when compared with alternative four- and five-drug regimens. When costs and outcomes are considered jointly, an enfuvirtide-based regimen is more cost efficacious than alternative regimens in this patient population.

The lifetime cost of current human immunodeficiency virus care in the United States.

OBJECTIVE: We sought to project the lifetime cost of medical care for human immunodefiency virus (HIV)-infected adults using current antiretroviral therapy (ART) standards. METHODS: Medical visits and hospitalizations for any reason were from the HIV Research Network, a consortium of high-volume HIV primary care sites. HIV treatment drug regimen efficacies were from clinical guidelines and published sources; data on other drugs used were not available. In a computer simulation model, we projected HIV medical care costs in 2004 U.S. dollars. RESULTS: From the time of entering HIV care, per person projected life expectancy is 24.2 years, discounted lifetime cost is Dollars 385,200, and undiscounted cost is Dollars 618,900 for adults who initiate ART with CD4 cell count < 350/microL. Seventy-three percent of the cost is antiretroviral medications, 13% inpatient care, 9% outpatient care, and 5% other HIV-related medications and laboratory costs. For patients who initiate ART with CD4 cell count < 200/microL, projected life expectancy is 22.5 years, discounted lifetime cost is Dollars 354,100 and undiscounted cost is Dollars 567,000. Results are sensitive to drug manufacturers' discounts, ART efficacy, and use of enfuvirtide for salvage. If costs are discounted to the time of infection, the discounted lifetime cost is Dollars 303,100. CONCLUSIONS: Effective ART regimens have substantially improved survival and have increased the lifetime cost of HIV-related medical care in the U.S.

Cost-effectiveness of enfuvirtide in HIV therapy for treatment-experienced patients in the United States.

Enfuvirtide (ENF) is the first of a new class of antiretrovirals (ARVs) known as the HIV fusion inhibitors. Two phase III studies of ENF, TORO 1 and TORO 2, demonstrated that ENF given in combination with optimized background (OB) therapy significantly improved virological response, increased the time to virological failure, and increased CD4-cell count compared with OB alone among highly treatment-experienced patients. The present study investigated the long-term clinical outcomes, costs, and cost-effectiveness of ENF. Outcomes, costs, and cost-effectiveness were estimated using a Markov model. Viral suppression and immune reconstitution were determined from the outcomes of the clinical trials. Time to immunological failure, time to AIDS-defining event (ADE), and time to death were estimated based on published mathematical models of disease progression. Costs were based on published estimates of the use and costs of ARVs, cost of managing ADEs, and cost of laboratory and other outpatient services. Cost-effectiveness was calculated as the incremental cost per year of life gained, adjusted for quality of life. The combined effects of an increase in CD4 count and delayed time to virological and immunological failure with ENF + OB were predicted to produce a mean life expectancy of 7.4 years from initiation of therapy, which was 1.8 years (1.5 quality-adjusted lifeyears [QALYs]) greater than the life expectancy associated with OB alone. The incremental cost-effectiveness of ENF + OB was estimated to be Dollars 24,604 per QALY. ENF is projected to increase time to immunological failure, delay onset of new AIDS-defining events, and increase life expectancy by more than 1.5 years among treatment-experienced HIV-infected patients. The cost-effectiveness of ENF is comparable to many existing treatment and prevention management strategies for HIV.

Cost-effectiveness of enfuvirtide for treatment-experienced patients with HIV in Italy.

BACKGROUND: Enfuvirtide (ENF) plus an optimized background (OB) antiretroviral regimen delays virological failure (VF), reduces HIV-1 viral load, and increases CD4 count compared with OB only in pretreated patients. PURPOSE: To forecast long-term outcomes, costs, and cost-effectiveness of ENF+OB vs. OB in the Italian health care system. METHOD: A Markov model was developed and clinical trial results on viral suppression and CD4 count were linked with data from HAART-era studies of the risk of AIDS-defining events (ADEs) and death. Resource data were obtained from Italian sources on direct medical costs. Cost-effectiveness was computed as the incremental cost per quality-adjusted life year (QALY) saved. RESULTS: Patients receiving ENF+OB were projected to experience a mean time to virological failure of 1.0 years vs. 0.5 years for OB and mean time to immunological failure of 3.1 years vs. 1.3 years for OB. Life expectancy and QALYs were greater for ENF+OB than OB by 1.8 and 1.5 years, respectively. Total lifetime medical cost was euro 126,487 for ENF+OB and euro 84,416 for OB, a difference of euro 42,071 due to the cost of ENF itself (euro 18,400) and the medical costs associated with additional life expectancy (euro 23,671). The incremental cost-effectiveness of ENF+OB was euro 23,721 per life year (euro 28,669 per QALY). CONCLUSION: ENF+OB is predicted to increase life expectancy at a cost per life year that is comparable to many well-accepted therapies in Europe.

Cost-effectiveness of enfuvirtide in treatment-experienced patients with advanced HIV disease.

OBJECTIVE: Enfuvirtide (ENF) has been shown to improve short-term virologic responses when given to highly treatment-experienced patients with advanced HIV disease. Because of the high cost of ENF compared with other antiretroviral agents, our objectives were to determine the potential long-term clinical impact and cost-effectiveness of ENF in these patients. METHODS: We used a computer simulation model of HIV disease to project life expectancy, quality-adjusted life expectancy, cost, and cost-effectiveness of ENF in treatment-experienced patients. Input data were from the T-20 versus Optimized Regimen Only (TORO) 1 and 2 trials, 2 studies comparing ENF plus an optimized background regimen (OBR) with an OBR alone. RESULTS: ENF plus an OBR increased projected discounted quality-adjusted life expectancy from 45.4 months with an OBR alone to 54.9 months, a difference of 9.5 quality-adjusted life-months. At the current annual ENF cost of US 18,500 dollars per year (in 2001 US dollars), the incremental cost-effectiveness ratio for ENF plus an OBR was US 69,500 dollars per quality-adjusted life-year (QALY) compared with an OBR alone. When 48-week virologic suppression rates for ENF plus an OBR were varied from a 50% reduction to a 250% increase in the suppression rate attributable to ENF, gains in quality-adjusted life expectancy ranged from 4.5 to 25.9 quality-adjusted life-months compared with an OBR alone, with cost-effectiveness ratios ranging from US 97,900 dollars per QALY to US 52,300 dollars per QALY gained. If ENF is continued after the HIV RNA level returns to the pretreatment baseline, the cost-effectiveness ratio increases to US 168,200 dollars per QALY. CONCLUSIONS: In highly treatment-experienced patients, ENF plus an OBR provides substantial gains in quality-adjusted life expectancy compared with an OBR alone. Although ENF plus an OBR is less cost-effective than other commonly used interventions in HIV disease, its use may be justified, given the poor prognosis of these patients and their otherwise limited options for antiretroviral therapy.

Enfuvirtide, a new treatment for HIV infection.

Enfuvirtide is the first in a new class of drugs called fusion inhibitors. It was recently approved in Canada for the treatment of patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. Current evidence on safety and efficacy is limited to 48-week studies. Two phase III trials found that in treatment-experienced patients failing antiretroviral treatment, the addition of subcutanous enfuvirtide to an optimized oral background antiretroviral regimen significantly reduced viral load and increased CD4 cell counts. Potential high cost and limited supply may reduce access to this treatment.

FDA news. Price criticized for new anti-HIV drug.

The FDA approved a new class of anti-HIV drugs that will benefit patients whose virus has become resistant to other treatments. But as states are facing funding shortfalls for AIDS drug assistance programs, activists say most patients won't be able to afford the drug.

T-20: most expensive AIDS drug ever at $25,000 per year?

A new kind of HIV treatment will probably cost several times as much as other AIDS drugs and be unavailable to many who need it.

Enfuvirtide (Fuzeon): the first fusion inhibitor.

With the number of people living with HIV infection increasing and the problems of drug resistance and long-term toxicity associated with current antiretroviral agents continuing, there is a growing need for new therapy options. Enfuvirtide is the first fusion inhibitor, a new class of drug, to be licensed for the treatment of HIV infection and is a welcome addition to the arsenal of antiretrovirals. This paper, which is the result of a multidisciplinary discussion meeting, reviews current practice in treating HIV infection, the clinical data available on enfuvirtide and discusses its introduction into clinical practice. Data available to date indicate that enfuvirtide is appropriate for use in patients who have previously taken nucleoside reverse transcriptase inhibitor (NRTI), non-NRTI and protease inhibitor containing regimens and are either intolerant of them or have experienced virological failure. Enfuvirtide should ideally be used while the patient still has other active drug options available to them to combine with enfuvirtide in an effective therapy regimen.