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Cost-Effectiveness of Maraviroc for Antiretroviral Treatment- Gob.Mx/00Cifras/Proy/ [Accessed May 5, 2008] View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Volume 13 • Number 8 • 2010 VALUE IN HEALTH Cost-Effectiveness of Maraviroc for Antiretroviral Treatment-Experienced HIV-infected Individuals in Mexicovhe_798 903..914 Iris Contreras-Hernandez, MD, MSc,1 Debbie Becker, MSc,2 Jeremy Chancellor, MSc,3 Felicitas Kühne, MSc,4 Joaquin Mould-Quevedo, PhD, MSc, MBA,5 Gabriela Vega, MSc,6 Shalaka Marfatia, BPharm, MS, MPH7 1Health Economics Research Unit, Social Security Mexican Institute, Mexico City, Mexico; 2Health Economics and Outcomes Research, i3 Innovus, Burlington, ON, Canada; 3Health Economics and Outcomes Research, i3 Innovus, Uxbridge, United Kingdom (at the time of the conduct of this study); 4Health Economics and Outcomes Research, i3 Innovus; PharmacoConsult, Uxbridge, United Kingdom; 5Pfizer Mexico, Mexico City, Mexico; 6Pfizer Mexico, Mexico City, Mexico (at the time of the conduct of this study); 7Pfizer Inc., New York, NY, USA (at the time of the conduct of this study) ABSTRACT Objective: Maraviroc is the first approved drug in a new class of antiret- undiscounted life expectancy and discounted quality-adjusted life expect- rovirals, the CCR5 antagonists. The objective of this study was to predict ancy from 7.54 to 8.71 years and 4.42 to 4.92 quality-adjusted life years the long-term clinical impact and cost-effectiveness of maraviroc in (QALYs), respectively, at an incremental cost of $228,215 (US$21,329). treatment-experienced adults with HIV/AIDS in Mexico. The resultant incremental cost-effectiveness ratio (ICER) was $453,978 Methods: The AntiRetroviral Analysis by Monte Carlo Individual Simu- (US$42,429) per QALY gained. The ICER was somewhat lower when lation (ARAMIS) model was adapted to the Mexican context to predict maraviroc was modeled in individuals susceptible to Յ2 components of clinical and economic outcomes of treating with optimized background OBT ($407,329; US$38,069), while the ICER was higher in individuals therapy (OBT) versus testing for viral tropism status and treating with susceptible to Ն3 OBT components ($718,718; US$67,171). OBT Ϯ maraviroc accordingly in treatment-experienced adults in Mexico. Conclusion: In treatment-experienced individuals with HIV/AIDS in Baseline characteristics and efficacy were from the MOTIVATE trials’ Mexico, maraviroc may be cost-effective, particularly in individuals with screening cohort. Costs and population mortality data were specific to limited options for active antiretroviral therapy (ART). Mexico. Results were reported from the perspective of health care payers Keywords: AIDS, anti-HIV agents, cost-effectiveness, economic model, in 2008 Mexican pesos (converted to 2008 US$ in parentheses). HIV, maraviroc, Mexico. Results: Compared to treatment with OBT alone, treatment with OBT Ϯ maraviroc contingent on tropism test result increased projected Introduction strains after long exposure to ART therapies, resulting in treat- ment failure. Acquired immunodeficiency syndrome (AIDS) continues to be a The newly developed drug maraviroc is the first of a class major health epidemic with an estimated 39.5 million people known as CCR5 antagonists. Maraviroc selectively and revers- living with human immunodeficiency virus (HIV) worldwide and ibly binds to CCR5 receptor on CD4+ cells, preventing interac- 2.9 million people dying from AIDS in 2006 [1]. Based on data tion with the gp120 protein of CCR5-tropic virions and from the Mexican National Center for the Prevention and the subsequent entry. In double-blind, placebo-controlled clinical Control of the HIV/AIDS, it was estimated in 2006 that 182,000 trials, maraviroc in addition to optimized background therapy people in Mexico were living with the disease [2,3]. In 2007, the (OBT) were compared to OBT alone in treatment-experienced World Health Organization (WHO) estimated HIV prevalence in adults infected with CCR5-tropic HIV-1 [7]. Patients treated Mexico, among adults aged 15 years and older, to be 244 per with maraviroc achieved a substantially greater viral load reduc- 100,000 population [4]. From 1992 to 1997, only social security tion than did patients treated with OBT alone (-1.84 and -0.78 beneficiaries had free access to antiretroviral therapies (ARTs) log10 copies/mL, respectively), with over twice the proportion of and HIV care in Mexico [5]. However, by 2006, accessibility to patients achieving undetectable levels of HIV-1 (56.1% and ART had increased to 78% of the infected Mexican population 22.5% with <400 copies/mL at 48 weeks) [8,9]. [6]. To predict the long-term clinical and economic impact of Currently, highly active antiretroviral therapy (HAART) rep- maraviroc as add-on therapy to OBT, we used the Anti Retroviral resents the mainstay among treatments for HIV-infected indi- Analysis by Monte Carlo Individual Simulation (ARAMIS) viduals, which suppress viral load, improve immune function, model [10] to analyze the cost-effectiveness of maraviroc for the and delay the progression of the disease. Since its introduction in management of individuals infected with only CCR5-tropic 1996, HAART has dramatically improved survival rates for indi- HIV-1 detectable, and who have evidence of viral replication and viduals with HIV infection. However, new classes of antiretrovi- HIV-1 strains resistant to multiple antiretroviral agents (The ral agents with novel mechanisms of action are now receiving ARAMIS cost-effectiveness model is the property of Pfizer Inc., greater consideration due to side effects and poor tolerability and is protected by US and international copyright laws. Unau- with existing agents and the emergence of drug-resistant viral thorized reproduction, modification, republication, distribution, or display of all, or any portion, of the ARAMIS cost- Address correspondence to: Debbie Becker, i3 Innovus, 1016 Sutton Drive, effectiveness model is prohibited). The analysis was conducted Burlington, ON, Canada L7L 6B8. E-mail: [email protected] from the perspective of the health care payer in Mexico to a 10.1111/j.1524-4733.2010.00798.x lifetime horizon. © 2010, International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 1098-3015/10/903 903–914 903 904 Contreras-Hernandez et al. Methods Analytic Overview The analysis was conducted using ARAMIS, a previously vali- dated and published computer-based microsimulation model of HIV disease progression and treatment [10]. The ARAMIS model was designed to be applicable to countries with well- developed systems for the care of individuals with HIV/AIDS, and was adapted to include Mexico-specific inputs. The model was used to extrapolate 48-week results from the MOTIVATE-1 and -2 studies and predict clinical and economic outcomes over a lifetime, using disease progression data derived from epidemio- logical cohort studies. Individuals screened for entry to the MOTIVATE trials (the “MOTIVATE screening cohort”) included adults with an HIV-1 RNA of greater than 5000 copies/mL despite at least 6 months of prior therapy with at least one agent from three ART classes or documented resistance or intolerance to at least one member of each class [8,9]. All indi- Figure 1 Markov state transition diagram for the ARAMIS model. OI, oppor- viduals in the MOTIVATE screening cohort were tested for viral tunistic infection. ↓ Denotes allowable transitions. ↑ Denotes transitions only tropism status, and only those in whom only CCR5 tropic virus allowable with treatment. was detectable were eligible for entry into the trial. The primary economic analysis was a comparison of two treatment strategies: 1) a “contingent maraviroc” strategy in untreated patients is known to be strongly related to the HIV which individuals would be treated with OBT, with or without viral load set point (i.e., the stabilized viral load in the postacute the addition of maraviroc according to viral tropism test results phase) (Table 1) [15]. As set point data were unavailable for the (“OBT Ϯ maraviroc”) versus 2) an “OBT alone” strategy of study population, baseline viral load was deemed to be a reason- treating the entire population with OBT alone, without testing able proxy for modeling the rate of decline of CD4+ cells in for tropism. Hence, the economic comparison was specified patients failing treatment. The loss of CD4+ cells in HIV-infected slightly differently from the design of the MOTIVATE trials, in individuals who are untreated or failing treatment drives transi- order to represent the ex ante policy decision on the use of tion through successively lower CD4+ states, while successful maraviroc in a treatment-experienced population, without prior antiretroviral treatment results in reconstitution of CD4+ cells knowledge of individuals’ tropism status. The primary outcomes and transitions from lower to higher CD4+ states. The CD4+ cell of the analysis were lifetime costs, life expectancy and quality- count trajectory and other aspects of each individual’s simulated adjusted life years (QALYs) resulting from each treatment strat- lifetime clinical history are recorded within the model. egy. Incremental cost effectiveness ratios (ICERs), including cost Independently of CD4+ cell count, the risk of an opportunis- per life year and cost per QALY gained, were calculated and tic infection and chronic HIV mortality is modified by history of reported in 2008 Mexican pesos (with values converted to 2008 an opportunistic infection and current exposure to antiretroviral US$ reported in parentheses). The analysis
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