Predicting HIV Care Costs Using CD4 Counts From Clinical Trials

Objective:To predict the effects of a new antiretroviral agent on the costs of care in a US HIV care setting.

Methods: Recent data on costs of patient care by CD4 count from 2 US cohorts (the HIV Research Network cohort and patients receiving primary care at the University of Alabama at Birmingham HIV clinic) were combined with CD4 count data from the POWER trials of the protease inhibitor darunavir. Patients in the POWER trials received either darunavir plus low-dose ritonavir (darunavir/r) or selected control protease inhibitors. The effects of rising CD4 counts with darunavir/r 600/100 mg twice daily on healthcare costs were predicted by using the US cohort data and published US antiretroviral drug prices.

Results: In the POWER trials, the overall cost of antiretroviral treatment including darunavir/r was $427 (1.4%) higher than that of combination treatment including control protease inhibitors. However, this increase may be offset by lower predicted costs of HIV care, leading to predicted net savings in overall costs of HIV treatment and care of $3613 per person-year based on data from the HIV Research Network cohort and $2836 per person-year based on data from the University of Alabama cohort. The prediction of cost savings is limited to the 12-month duration of the trial.

Conclusion: By raising the CD4 count, new antiretrovirals could lower healthcare costs for HIVinfected people. This type of analysis could be used for other antiretrovirals, for a short-term assessment of overall budget impact.

(Am J Manag Care. 2007;13:524-528)

By raising the CD4 count, new antiretrovirals could lower healthcare costs for HIV-infected people.

Effects of rising CD4 counts with the protease inhibitor darunavir plus lowdose ritonavir (darunavir/r) on healthcare costs in a US HIV care setting were predicted by using US cohort data, published US antiretroviral drug prices, and CD4 count data from the POWER trials of darunavir/r.

The higher cost of darunavir/r was offset by lower predicted costs of HIV care over the 12-month duration of the trial.

This type of analysis could be used for other antiretrovirals, for a short-term assessment of overall budget impact.

Patients with persistently low CD4 counts on antiretroviral treatment have a higher risk of progression to AIDS and related death.^1,2 The introduction of highly active antiretroviral treatment (HAART), which raised CD4 counts, led to reductions in costs of patient care.^3,4 Costs of patient care in the United States by CD4 count recently were analyzed in the HIV Research Network (HIV RN) cohort⁵ and the University of Alabama cohort.⁶

For treatment-naïve patients, a range of combination treatments are available, which can lead to a high proportion of patients achieving undetectable HIV RNA levels, followed by long-term rises in CD4 counts.^7,8 However, the proportion of treatment-experienced patients who respond to treatment is limited by drug resistance. Treatment-experienced patients take a wide range of complex combinations of antiretroviral drugs.⁸

This analysis was conducted to predict the effects of a new antiretroviral agent, darunavir, on the costs of care in a US HIV care setting. Darunavir is an HIV protease inhibitor with activity against protease inhibitor—resistant HIV.⁹ The costs of antiretroviral treatment from the POWER trials, where patients were treated either with darunavir plus low-dose ritonavir (darunavir/r) or selected control protease inhibitors, were compared with costs of patient care using cost data from the 2 US cohort studies.

METHODS

The costs of patient care from 2 US cohorts were combined with antiretroviral costs and CD4 count data from the POWER trials. The effects of rising CD4 counts with darunavir/r treatment on healthcare costs were predicted using the US cohort data and published US antiretroviral drug prices.

During 2003, 635 adult patients (age >18 years) who were in longitudinal HIV primary care at one of 14 HIV RN sites participated in face-toface interviews. Comprehensive data were obtained regarding all medications used (prescription and nonprescription), as well as inpatient, outpatient, and emergency department utilization. Computation of costs was based on nonantiretroviral medications (Red Book average wholesale price–15%), inpatient days, outpatient visits, and emergency department utilization (HIV Cost & Services Utilization Study costs).¹⁰

All encounters (except emergency department visits) of University of Alabama at Birmingham HIV clinic patients with the University of Alabama at Birmingham hospital system from March 1, 2000, to March 1, 2001, were analyzed. Medication expenditures were determined on the basis of 2001 average wholesale prices. Hospitalization expenditures were determined on the basis of 2001 Medicare diagnostic-related group reimbursement rates. Clinic expenditures were determined on the basis of 2001 Medicare current procedural terminology reimbursement rates.

Costs from both cohorts were inflation adjusted to 2005 values by using standard consumer price index assumptions.

POWER Trials: CD4 and Cost DataThe POWER 1 and 2 trials recruited patients with >1000 copies of HIV RNA per milliliter; prior exposure to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors; and at least 1 primary protease inhibitor mutation.¹¹ Patients were given either darunavir/r or investigator-selected control protease inhibitors.^9,11,12 In addition, all patients were given optimized background antiretrovirals: nucleoside analogues and in some cases the fusion inhibitor enfuvirtide (T-20).

Of the 4 dosages of darunavir/r studied, the 600/100 mg twice-daily dosage showed the strongest efficacy and was selected for further development. Therefore, data from the darunavir/r 600/100 mg twice daily (n = 131) and control protease inhibitor (n = 124) arms of the POWER trials were used in this analysis. The baseline mean HIV RNA and median CD4 counts were 4.6 log₁₀ copies per milliliter and 153 cells per microliter, respectively, for the darunavir/r group, versus 4.5 log₁₀ copies per milliliter and 163 cells per microliter, respectively, for the control protease inhibitor group. Darunavir/r 600/100 mg twice daily led to a rise in CD4 count of 102 cells and to 45.5% of patients having fewer than 50 copies of HIV RNA per milliliter at Week 48, compared with a rise in CD4 count of 19 cells and 10% of patients having fewer than 50 copies of HIV RNA per milliliter at Week 48 in the control protease inhibitor arm. There was no overall difference in the incidence or severity of adverse events by treatment arm.

Table

In the POWER trials, the proportion of patients with CD4 counts in the categories used in the HIV RN and University of Alabama cohorts was assessed by treatment arm for patient visits from baseline to Week 48 (). The cost of antiretrovirals in the POWER trials was calculated using the most recent US prices (March 2006, Medi-Span, Indianapolis, Ind). For darunavir, the list price at launch in June 2006 was used. A weighted average of the antiretroviral treatment use by arm was used to calculate mean annual per patient costs of antiretrovirals. For this analysis, patients were assumed to continue taking all treatments assigned at baseline for a full 52 weeks. The cost of ritonavir 100 mg daily was increased from US $624 per patient-year to US $3128 per patient-year in late 2003. However, public payers in the United States were not affected by this price increase. Therefore, the original cost of ritonavir 100 mg daily (US $624 per patient-year) was retained for this analysis.

DISCUSSION

In the POWER trials, the overall cost of antiretroviral treatment including darunavir/r was $427 (1.4%) higher than that of combination treatment including control protease inhibitors. However, this increase in antiretroviral drug cost may be offset by lower predicted costs of HIV care, leading to a predicted net saving in overall costs of HIV treatment and care of $3613 per person-year based on data from the HIV RN cohort and $2836 per person-year based on data from the University of Alabama cohort.

This analysis is based on data from antiretroviral-experienced patients, in whom darunavir/r treatment showed a significant efficacy benefit over alternative protease inhibitors. Clinical trials are under way to evaluate darunavir/r compared with other protease inhibitors in less experienced or treatment-naïve patients, and it is currently unknown whether efficacy benefits also will be seen in these populations. Patients in the POWER trials had relatively low CD4 counts at baseline. For populations with higher overall baseline CD4 levels, the same efficacy benefits may not be seen. In addition, the analysis does not take into account second-line treatments taken after initial failure of the randomized treatment. The rate of virologic failure was higher in the control protease inhibitor arm than in the darunavir/r arm. Virologic failure is a persistently detectable HIV RNA level despite good adherence to antiretroviral treatment. Treatments that lead to higher rates of resistance development at treatment failure may compromise future treatment options.^13,14 Treatment-experienced patients with virologic failure may need more complex and expensive salvage options over the longer term, potentially involving more use ofenfuvirtide, which could increase costs for the control protease inhibitor arm.

The prediction of cost savings is limited to the 12-month duration of the trial during which information on CD4 counts was available. Longerterm follow-up is needed to make predictions of subsequent benefits, and this analysis could be repeated once

Andrew Hill, PhD, Pharmacology Research Laboratories, University of Liverpool, 70 Pembroke Place, Liverpool, L69 3GF, United Kingdom. E-mail: microhaart@aol.com.1.The PLATO Collaboration 2004. Predictors of trend in CD4 positive T-cell

5. Gebo K, Fleishman J, Conviser R, et al. Contemporary costs of HIV healthcare in the HAART era. In: Program and abstracts of the 13th Conference on Retroviruses and

8. Hammer SM, Saag MS, Schechter M, et al. Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel. JAMA.

14. Simpson K, Luo M, Chumney E, Sun E, Brun S, Ashraf T. Cost-effectiveness

15. Gallant J, Staszewski S, Pozniak A, et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviralnaïve patients: a 3 year randomized trial. JAMA. 2004;292:191-201.

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