Abstract and Introduction
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 log10 copies/mL (p < 0.001 for enfuvirtide vs each non-enfuvirtide group) and +102, +57 and +52 cells/mm3 (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 $US35 624, $US27 549 and $US30 624; and the costs per 0.50 log10 copies/mL HIV RNA decrease were $US9872, $US15 542 and $US24 907 (p < 0.05 for enfuvirtide vs each non-enfuvirtide subgroup) for groups 1, 2 and 3, respectively. The costs per 25 cells/mm3 CD4 count increase were $US8722, $US12 127 and $US14 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 $US3124 for HIV RNA reduction and $US3239 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.
Over the past decade, specialty drugs (i.e. drugs that require special handling, dispensing or administration) have been made available for the treatment of various conditions.[1,2,3] Such drugs often reflect significant clinical advances beyond current standards of care, which is further mirrored by their higher cost. For example, in 2003 the annual costs for non-specialty drugs in the US increased 10-15%, while the annual costs for specialty drugs increased 27-39%.[4,5] Increasing demand for higher cost drugs may pose a considerable financial burden to insurance providers, public health departments or patients.
Treatment of HIV infection consists of use of various combinations of antiretroviral agents (ARVs) from the four classes of agents currently available: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs); non-nucleoside reverse transcriptase inhibitors (NNRTIs); protease inhibitors (PIs) and entry inhibitors. In patients with limited or no prior ARV exposure, three-drug/two-class regimens are common, while patients with prior exposure to three classes may require four or more ARVs from at least three classes for sufficient anti-HIV activity.[6,7,8,9] The necessity for use of greater numbers of ARVs in advancing patients is further complicated by the need to perform costly resistance tests to help guide the selection of active drugs.[10,11] Despite a significant reduction in HIV-associated morbidity and mortality over the past decade, fiscal challenges are increasing and decisions regarding reimbursement for combination ARV therapy are becoming more complicated. The challenge, from both payer and societal points of view, is the prioritisation of resources in limited budget settings and the development of metrics that can evaluate the cost effectiveness of different therapeutic interventions aimed at various HIV-infected patient populations.
The initial step of HIV viral entry is the attachment of the virus to the CD4 molecule located on the host cell, followed by binding to a co-receptor. Once bound, the virus fuses with the cell membrane and transfers the nucleocapsid containing viral RNA into the host cell cytoplasm. Entry inhibitors prevent viral entry by interfering with any one of these steps. Enfuvirtide is the first and currently only available fusion inhibitor, the most recently introduced class of ARVs. Enfuvirtide is a novel, synthetic, 36-amino acid peptide that inhibits the fusion of the HIV with the CD4+ host cell, thereby preventing entry and viral replication. Two international, multicentre, randomised, controlled clinical trials (T-20 vs Optimized Regimen Only Study 1 and 2 [TORO 1 and 2]) demonstrated that in patients with prior exposure to at least one ARV from each of the three previously available ARV classes, inclusion of enfuvirtide with an optimised ARV regimen provided significant virological and immunological benefit through 48 weeks compared with patients who received an optimised ARV regimen without enfuvirtide.[6,7,13]
The development and market availability of enfuvirtide was accompanied by a controversial health economics discussion. While initial responses primarily focused on costs and drug price,[14,15] a more comprehensive assessment that applied standard health economic methods and provided modeling of clinical outcomes beyond clinical trial duration and the estimated cost-effectiveness ratios was conducted. These analyses included an estimate of increased life expectancy (1.8 years) in enfuvirtide-treated patients as well as an estimated cost per quality-adjusted life-year (QALY) gained of $US24 604, which is consistent with the incremental cost-effectiveness ratios that were reported when the third class of drugs, PIs, was first introduced.[17,18] Another cost-effectiveness study of enfuvirtide reported a higher cost-effectiveness ratio ($US69 500 per QALY gained). These studies used Markov-modeling techniques to derive costs per projected long-term outcome. Additionally, both of these analyses evaluated the use of enfuvirtide as an incremental, 'add-on' therapy, as compared with no add-on therapy.
In the TORO studies,[6,7,13] the ARV regimen (optimised background [OB] regimen) was selected by individual investigators in a controlled clinical trial setting prior to their knowledge of randomisation results (enfuvirtide vs non-enfuvirtide). This may not be reflective of ARV selection strategies in clinical practice, where drug choices are made in an unblinded, uncontrolled environment. For instance, therapeutic decision making for triple class-experienced patients involves selections of drug options based on multiple considerations, including the likelihood of antiviral activity in those patients harbouring drug-resistant variants, individual patient safety/tolerability concerns, pharmacological limitations, drug coverage/access issues and cost effectiveness. This analysis was conducted using the perspective of a healthcare practitioner who is concerned about both clinical outcomes of patients and the costs of treatment. In order to determine and compare virological and immunological responses and the cost of enfuvirtide versus other ARV options, a comparative cost-effectiveness analysis was performed. The primary objective of this analysis was to assess the cost per unit change in effectiveness (HIV RNA decrease and CD4 count increase) of enfuvirtide-inclusive regimens versus other ARV regimens.
Clin Drug Invest. 2007;27(7):469-479. © 2007 Adis Data Information BV
This research was presented in part at the XVI International AIDS Conference 13-18 August 2006, Toronto, Canada (Abstract TuPe0070).
Cite this: Cost-Efficacy Comparison among Three Antiretroviral Regimens in HIV-1 Infected, Treatment-Experienced Patients - Medscape - Jul 01, 2007.