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Cost-effectiveness of antiretroviral regimens in the World Health Organization's treatment guidelines: a South African analysis |
Bendavid E, Grant P, Talbot A, Owens DK, Zolopa A |
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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 The objective was to assess the cost-effectiveness of first-line antiretroviral therapy guidelines recommended by the World Health Organization (WHO), in resource-limited settings. The authors concluded that their results supported the decision to eliminate stavudine, lamivudine, and nevirapine from the guidelines. Tenofovir, lamivudine, and nevirapine was likely to be cost-effective, if accessible and acceptable. Zidovudine, lamivudine, and efavirenz should be not be recommended. The methods were robust, which enhances the validity of the authors’ conclusions. Type of economic evaluation Study objective The objective was to assess the cost-effectiveness of first-line antiretroviral therapy (ART) guidelines recommended by the World Health Organization (WHO) in resource-limited settings for patients with HIV who had not received treatment before. Interventions Five first-line ART regimens were considered: tenofovir, lamivudine, and efavirenz (TLE); tenofovir, lamivudine, and nevirapine (TLN); zidovudine, lamivudine, and efavirenz (ZLE); zidovudine, lamivudine, and nevirapine (ZLN); and stavudine, lamivudine, and nevirapine (SLN). The first four strategies were recommended by WHO. SLN was not recommended due to its toxicities, but was commonly used in resource-limited settings. Location/setting South Africa/primary and secondary care. Methods Analytical approach:
The analysis was based on a published mathematical model of the clinical course of HIV-infected individuals. A lifetime horizon was considered. The authors stated that a societal perspective was adopted.
Effectiveness data:
The clinical data were from a selection of relevant studies. The rates of virologic suppression and toxicities were the most important inputs. The treatment effects were from clinical trials conducted in developed countries. Most of these data were from two long-standing trials; one compared tenofovir with stavudine regimens and the other compared zidovudine with tenofovir regimens. The data on adverse events were from long-term follow-up studies of clinical trials, where possible. Otherwise, African observational studies were used. The epidemiological inputs were from South African sources and the patients’ characteristics were from Cape Town study cohorts.
Monetary benefit and utility valuations:
The utility values for HIV conditions and treatment-related toxicities were from published sources, including the clinical trials that supplied the effectiveness estimates, South African sources, and US studies.
Measure of benefit:
Quality-adjusted life-years (QALYs) were the summary benefit measure and they were discounted at an annual rate of 3%. Life expectancy and the average number of opportunistic diseases were reported.
Cost data:
The economic analysis included the costs of highly active ART, the management of toxicity, and the treatment of AIDS (in-patient stay, monitoring, and out-patient visits). The HIV costs depended on cluster of differentiation (CD) 4 cell count and the occurrence of severe opportunistic disease. The in-patient and out-patient costs for HIV care were from a South African study and the costs of ART were from the WHO Global Price Reporting Mechanism database. All costs were in US dollars ($) and the price year was 2009. A 3% annual discount rate was applied.
Analysis of uncertainty:
One-way sensitivity analyses were carried out on the rates of treatment failure, the toxicity rates, the quality-of-life weights, and the cost of ART. Published and assumed ranges of values were considered. A first-order probabilistic sensitivity analysis was performed, varying all the parameters simultaneously to create means and confidence intervals. Results The projected QALYs were 10.47 with ZLN, 10.31 with SLN, 11.08 with TLN, 10.69 with ZLE, and 11.27 with TLE. The costs were $7,711 with ZLN, $7,824 with SLN, $8,348 with TLN, $8,748 with ZLE, and $9,479 with TLE.
Both SLN and ZLE were dominated as they were less effective and more expensive than another strategy. ZLN was the base strategy and the incremental cost per QALY gained was $1,045 with TLN over ZLN and $5,950 with TLE over TLN. The acceptable cost-effectiveness threshold of the gross domestic product per capita in South Africa was $5,800 per QALY gained.
The sensitivity analysis showed that TLE was cost-effective over TLN if virologic failure was at least 1.5 times more likely with TLN. The quality-of-life weights for lipoatrophy were a driver of the analysis, but SLN remained dominated as long as its utility was below 0.95.
In 96% of simulations, ZLN dominated SLN. The incremental cost per QALY gained with TLE over TLN was within the acceptable threshold in 52% of simulations. Authors' conclusions The authors concluded that their results supported the decision to eliminate SLN from the WHO guidelines for first-line regimens, while TLN was likely to be cost-effective, if accessible and acceptable. ZLE was unlikely to be cost-effective and should be not be recommended. CRD commentary Interventions:
A justification for the selection of the comparators was given. The first four treatments were recommended by the WHO, and the fifth treatment was commonly used in developing countries even though it was no longer recommended by the WHO.
Effectiveness/benefits:
The treatment effects were mainly from clinical trials conducted in developed countries, which are likely to have had high internal validity. The authors stated that these data were transferable to developing countries, on the basis of recent findings. The adverse events, which were a key input given the toxicity profile of SLN, were from a long-term follow-up of clinical trials and observational studies in South Africa. All these sources appear to have been appropriate and representative of the setting. Uncertain parameters were extensively varied in the sensitivity analyses. The utility values were from published sources, but the methods used to derive them were not reported. QALYs were a valid benefit measure; they capture the impact of the disease on survival and quality of life. Other outcomes, such as life expectancy, were reported.
Costs:
A wide range of cost categories was included, but productivity losses were not assessed and were relevant for the societal perspective. Unit costs were reported for some items, but limited resource quantities were provided, which reduces the transparency of the analysis. The data sources were partly described and reflected the setting of a country with limited resources. Reflation exercises will be possible as the price year was reported. The impact of variations in the cost estimates was tested in the sensitivity analyses.
Analysis and results:
The results were clearly presented. An incremental approach was used to synthesise the costs and benefits, to identify the dominated strategies.The uncertainty was satisfactorily investigated, in deterministic and probabilistic sensitivity analyses, and the results were clearly illustrated. Extensive details of the model and the data sources were presented in the online appendix. Conventional discounting was applied. The authors acknowledged that their findings were specific to South Africa and will be difficult to transfer to other settings.
Concluding remarks:
The methods were robust, which enhances the validity of the authors’ conclusions. Bibliographic details Bendavid E, Grant P, Talbot A, Owens DK, Zolopa A. Cost-effectiveness of antiretroviral regimens in the World Health Organization's treatment guidelines: a South African analysis. AIDS 2011; 25(2): 211-220 Indexing Status Subject indexing assigned by NLM MeSH Adolescent; Adult; Antiretroviral Therapy, Highly Active /economics /methods; CD4 Lymphocyte Count; Cost-Benefit Analysis /economics /statistics & Female; HIV Infections /drug therapy /economics /mortality; Health Resources /economics /statistics & Humans; Male; Middle Aged; Models, Theoretical; Quality-Adjusted Life Years; South Africa /epidemiology; Viral Load; World Health Organization; Young Adult; numerical data; numerical data AccessionNumber 22011000240 Date bibliographic record published 12/10/2011 Date abstract record published 07/02/2012 |
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