Cost Effectiveness of Lopinavir/Ritonavir Compared with Atazanavir plus Ritonavir in Antiretroviral-Experienced Patients in the US

Kit N. Simpson; Walter J. Jones; Rukmini Rajagopalan; Birgitta Dietz


Clin Drug Invest. 2007;27(7):443-452. 

In This Article

Abstract and Introduction


Objective: To estimate the cost effectiveness and long-term combined effects of HIV disease and antiretroviral (ARV) therapy-related risk for coronary heart disease (CHD) on quality-adjusted survival and healthcare costs for ARV-experienced patients.
Methods: A previously validated Markov model was updated and supplemented with the Framingham CHD risk equation. The representative patient in the model was male, aged 37 years and had a baseline 10-year CHD risk of 4.6%. Patients started with either lopinavir/ritonavir (LPV/r) or ritonavir-boosted atazanavir (ATV+RTV) as the protease inhibitor (PI). The proportions of patients with viral suppression below 400 and 50 copies/mL, respectively, at week 48 reported in clinical trials were used to estimate the differences between these two therapies. The daily ARV costs were $US24.60 for LPV/r capsules (2005 costs) and $US26.54 for LPV/r tablets (2006 costs), $US29.76 for ATV and $US8.57 for ritonavir (2005 costs). Costs of other ARV drugs were taken from average wholesale drug reports for 2005. The cost of AIDS events was estimated from Medicaid billing databases and reflected a medical care system perspective and 2005 treatment costs. Cost-effectiveness calculations assumed a lifetime time horizon. The effects of different model assumptions were tested in a multiway sensitivity analysis by combining extreme values of parameters.
Results: The model estimated a clinical and economic advantage to using LPV/r over ATV+RTV, which varied depending upon the use of LPV/r capsules or tablets. Using LPV/r capsules was comparatively beneficial for ARV-experienced patients in quality-adjusted life-months (QALMs) of 4.6 (corrected for differences in CHD risk) compared with ATV+RTV. In addition, there were 5- and 10-year overall per-patient cost savings of $US17 995 and $US21 298, respectively. Estimates for the LPV/r tablet formulation approved in 2005 (assuming similar efficacy) improved cost savings over 5- and 10-year periods to $US19 598 and $US23 126 per patient, respectively, because of a drug price differential. Sensitivity analysis tested numerous assumptions about the model cost and efficacy parameters and found that the results were robust to most changes. Model limitations were the uncertainty associated with the model parameters used.
Conclusion: LPV/r appears to be a highly cost-effective regimen relative to ATV+RTV for the treatment of HIV. The long-term CHD risk associated with LPV/r was minimal compared with the increased risk of AIDS/death and costs projected for a less efficacious PI-based regimen.


There have been considerable improvements in the clinical prognoses for HIV-infected individuals, particularly in recent years with the rise of multidrug therapies. However, these patients usually have to adjust therapies frequently as the virus adjusts to the treatment combination.[1,2] It is becoming increasingly difficult to choose follow-up antiretroviral (ARV) therapies because consideration must be given to numerous factors, including efficacy, adverse event risk, resistance concerns and treatment costs. The efficacy of a regimen and its durability, as demonstrated in controlled clinical trials and long-term follow-up studies, must be reassessed in the light of reported adverse effects, ease of adherence to the recommended dosage schedule, the regimen's likelihood of causing viral resistance to subsequent therapies, patient preferences, and the presence of co-morbid conditions and risk factors that are specific to each individual patient. Increased risk of coronary heart disease (CHD) is of special concern for the selection of an ARV regimen, because regimens may impact CHD risk factors differently.[2]

If treatment by a new drug combination can prevent or delay the onset of later disease stages, there may be major cost savings through the reduction of more intensive healthcare, both in terms of a less costly ARV regimen and in terms of fewer AIDS events. The patient may also significantly benefit through increased quality-adjusted life-years (QALYs), since they live longer periods of time before needing a switch to salvage therapy.

This study estimates the cost effectiveness and long-term combined effects of HIV disease, the benefits of ARV therapy and ARV-related risk for heart disease of an ARV regimen containing lopinavir/ritonavir (LPV/r) compared with another regimen containing atazanavir with ritonavir (ATV+RTV), where ritonavir is used for pharmacokinetic enhancement ('boosting') of ATV drug concentrations for ARV-experienced patients. We chose to examine the comparison of LPV/r and ATV+RTV for two reasons. Firstly, we have previously modeled the outcomes for ATV and LPV/r in ARV-naive patients and found both health and economic benefits for the LPV/r regimen[3] and would like to examine the model estimates for ARV-experienced patients. Secondly, this comparison gives us the opportunity to explore the expected long-term health and economic impacts of differences in viral load suppression to below 50 copies/mL reported by Mocroft and colleagues.[4]

We used a Markov model[5] that integrates data and information from the epidemiology of HIV and CHD, combined with clinical trial data under a clearly specified set of assumptions to estimate differences in QALYs (which have been reported in quality-adjusted life-months [QALMs] in places where length of survival is discussed) and costs for the two regimens.


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