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Scaling up the 2010 World Health Organization HIV treatment guidelines in resource-limited settings: a model-based analysis |
Walensky RP, Wood R, Ciaranello AL, Paltiel AD, Lorenzana SB, Anglaret X, Stoler AW, Freedberg KA, Cost Effectiveness of AIDS Complications International Investigators |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. CRD summary This study examined the cost-effectiveness of 2010 guidelines from the World Health Organization for HIV treatment, in resource-limited settings where their immediate implementation was not feasible. The authors concluded that antiretroviral therapy initiation at a cluster of differentiation (CD) 4 cell count of less than 350 cells per microlitre produced the longest survival and was highly cost-effective, followed by switching to tenofovir, and then adding second-line therapy. The methods were valid and the authors’ conclusions appear to be robust. Type of economic evaluation Cost-effectiveness analysis Study objective This study examined the cost-effectiveness of the 2010 guidelines from the World Health Organization (WHO) for HIV treatment in resource-limited settings, where the immediate implementation of these guidelines was not feasible. The analysis focused on evaluating stepwise implementation scenarios. Interventions The reference strategy was the WHO 2006 guidelines, where all HIV patients who had WHO stage III or IV disease, started on stavudine-based antiretroviral therapy and received one line of treatment. The 2010 WHO guidelines recommended more sequences of antiretroviral therapy, routine cluster of differentiation (CD) 4 cell counts, earlier initiation of therapy, and the replacement of stavudine with the less-toxic drug tenofovir. There were 12 possible combinations of the following: stavudine or tenofovir (nucleoside analogues); antiretroviral therapy initiation based on WHO stage, CD4 less than 200 cells per microlitre (μL), or CD4 less than 350 cells/μL; and one or two regimens, or lines, of antiretroviral therapy. A strategy with no antiretroviral therapy was considered. Location/setting South Africa/primary care. Methods Analytical approach:The analysis was based on the published Cost Effectiveness of AIDS Complications (CEPAC) International model, which was a Monte Carlo simulation of the natural history and treatment of HIV disease. A lifetime horizon was considered. The authors stated that a modified societal perspective was adopted.
Effectiveness data:The clinical data were identified by a systematic review of the literature in commonly used electronic databases. Meta-analysis was used to pool the evidence from multiple robust sources, or the source with the most robust methods was selected. Most of the epidemiological evidence was from South African sources. The natural history of disease was from a large cohort study. Treatment efficacy and failure (inefficacy and toxicity) were the key inputs for the model and these data were mainly from clinical trials.
Monetary benefit and utility valuations:Not considered.
Measure of benefit:Life-years were the summary benefit measure and they were discounted at an annual rate of 3%.
Cost data:The economic analysis included the direct medical costs of HIV, such as in-patient days, out-patient visits, medications, and laboratory tests. The cost and resource use data were from published sources, most of which related directly to South Africa. The costs were estimated in South African rand and converted to US dollars ($). Future costs were discounted at an annual rate of 3% and the price year was 2008.
Analysis of uncertainty:One-way sensitivity analyses were carried out to identify the drivers of the model, which were then investigated in multivariate sensitivity analyses. The ranges of values were generally from the literature. The time horizon for the analysis was varied. Results After excluding the dominated strategies, which were more expensive and less effective than another strategy, the discounted costs were $5,550 with stavudine, started at CD4 count under 350/μL, and one line of therapy, $6,870 with tenofovir, under 350/μL, and one line; and $12,820 with tenofovir, under 350/μL, and two lines. The expected survival was 104.3 months with stavudine, under 350/μL, and one line; 118.3 months with tenofovir, under 350/μL, and one line; and 148.4 months with tenofovir, under 350/μL, and two lines.
The incremental cost per life-year gained was $610 with stavudine, under 350/μL, and one line; $1,140 with tenofovir, under 350/μL, and one line; and $2,370 with tenofovir, under 350/μL, and two lines.
Variations in the mean CD4 cell count for the cohort did not alter the base-case findings substantially. A key driver of the model was the price of tenofovir, while the results were less sensitive to variations in the price of the second-line regimen. Authors' conclusions The authors concluded that, in settings where the immediate implementation of the WHO treatment guidelines was not feasible due to limited resources, antiretroviral therapy initiation at a CD4 cell count under 350 cells/μL was associated with the longest survival, and was highly cost-effective. Switching to tenofovir was the next option that should be introduced, and making a second line of therapy available provided more benefit, but at the greatest cost. CRD commentary Interventions:The rationale for the selection of the comparators was clear as all the possible treatment combinations were considered, for countries where the immediate implementation of the WHO treatment guidelines was not feasible.
Effectiveness/benefits:A valid approach was used to identify the relevant sources of data, as the literature was systematically reviewed and the data were meta-analysed, where required. The treatment effect was mainly from clinical trials that usually have high internal validity, while the epidemiological data were appropriately from South African large cohort studies. More details of these studies would have been useful to fully assess the validity of these data. Expected survival was a valid benefit measure as this was the main outcome of the HIV treatment programmes. Life-years allow cross-disease comparisons to be made. Quality-adjusted life-years would have been more appropriate, but were not possible because of a lack of quality of life estimates.
Costs:The cost categories were consistent with the modified societal perspective, which did not include direct non-medical and indirect costs. A list of cost items was reported and key data on unit costs were presented. The data sources were specific to the study setting and might not be generalisable to other countries. The cost data were varied in the sensitivity analysis. Other details, such as the price year and currency conversions, were reported. A standard discount rate was applied to future costs.
Analysis and results:The results were extensively presented, with more information in an online appendix. The uncertainty was investigated, using a deterministic approach, which initially focused on individual inputs and then assessed the impact of simultaneous parameter variations. The results of the sensitivity analyses were generally well reported. The policy implications for countries with limited resources were reported: antiretroviral therapy initiation at a CD4 count of less than 350 cells/μL was the first option, then a switch from stavudine to tenofovir, and lastly the introduction of a second-line antiretroviral therapy.
Concluding remarks:The methods were valid and the authors’ conclusions appear to be robust. Funding Supported by the National Institute of Allergy and Infectious Diseases, the National Institute of Drug Abuse, and the Doris Duke Charitable Foundation, USA. Bibliographic details Walensky RP, Wood R, Ciaranello AL, Paltiel AD, Lorenzana SB, Anglaret X, Stoler AW, Freedberg KA, Cost Effectiveness of AIDS Complications International Investigators. Scaling up the 2010 World Health Organization HIV treatment guidelines in resource-limited settings: a model-based analysis. PLOS Medicine 2010; 7(12):e1000382 Indexing Status Subject indexing assigned by NLM MeSH Acquired Immunodeficiency Syndrome /drug therapy; Adult; Anti-HIV Agents /administration & Cost-Benefit Analysis; Female; Guidelines as Topic; HIV Infections /drug therapy; Humans; Male; Models, Theoretical; World Health Organization; Young Adult; dosage /economics /therapeutic use AccessionNumber 22011000084 Date bibliographic record published 06/04/2011 Date abstract record published 29/06/2011 |
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