Baseline CD4 cell count, rate of CD4 cell decline off therapy, and ART efficacy had the greatest impact on survival outcomes, although because longer or shorter survival incurred greater or fewer costs, these parameters did not have a major influence on cost-effectiveness. Baseline CD4 count was varied from that of a cohort with WHO stage II disease (mean CD4 count = 408 cells/μL) to that of a cohort with stage IV disease (mean CD4 count = 132 cells/μL), resulting in mean life expectancies with treatment with 2 lines of ART varying from 9.83 to 6.39 years. Varying the rate of CD4 cell decline from twice to one half of the base case rate gave life expectancies with 2 lines of ART ranging from 8.14 to 10.39 years. Finally, varying first-line ART efficacy in terms of viral suppression at 6 months from 46% to 94% gave life expectancies ranging from 7.21 to 9.85 years. To test the impact of calibrated mortality rates, we varied the probability of chronic AIDS death, stratified by CD4 cell count, from twice to one half of the base case, which yielded life expectancies ranging from 8.21 to 10.06 years.
The cost of second-line ART and the strategies used to switch therapy had the greatest impact on cost-effectiveness. Decreasing second-line ART cost yielded substantially lower cost-effectiveness ratios. When the cost of second-line ART was decreased to the generic prices recently reported by Médecins Sans Frontières ($172 per month from the base case of $515 per month),30 the incremental cost-effectiveness ratio for 2 lines of ART initiated when the CD4 count was <350 cells/μL with cotrimoxazole decreased to $3530 per YLS (see Fig. 1). At the generic cost for second-line ART, total lifetime costs decreased from the base case result of $17,020 to $9290, with second-line ART costs representing 42% of the total cost of lifetime medical care. Switching from first- to second-line therapy only with an opportunistic disease (removing the criterion of CD4 cell count decrease by 50% from on-treatment peak) decreased survival to 8.17 years from the base case survival of 9.20 years, with a cost-effectiveness ratio of $70,800 per YLS (Table 3).
To provide lifetime treatment and care to the currently identified 1070 HIV-infected persons living in the OECS with the best practice strategy (2 lines of ART when the CD4 count was <350 cells/μL with cotrimoxazole), $18.2 million would be required region-wide for medical care and drugs, or $2.0 million per year over the mean length of survival of 9.20 years (Table 4). Four percent of that amount (or $685,500) is required over the next year. If second-line drug prices in the OECS were reduced to those currently available for generic second-line drugs elsewhere, the regional estimate for lifetime care cost would decrease by 45%, to $9.9 million, with $678,800 required over the next year (see Table 4).
We used the best available Caribbean data and a published computer simulation model of HIV disease to estimate the survival, cost-effectiveness, and budgetary implications of different strategies for HIV care in the OECS. The most effective strategy included 2 sequential lines of ART, initiated when the CD4 count was <350 cells/μL, with cotrimoxazole when the CD4 count was <200 cells/μL; this strategy was cost-effective throughout the OECS and provided a mean survival gain of 6.90 years per person compared with no treatment. Although this strategy was cost-effective by international standards and consistent with current regional guidelines, the cost of second-line ART comprised 68% of total lifetime care costs, making the 2-line strategy much less affordable than a 1-line strategy. Early initiation of treatment with 1 line of ART provided 89% of the life expectancy achieved with 2 lines of ART at one third of the cost. Projected costs for the complete scale-up of universal lifetime access to treatment to currently identified patients in the OECS were $18.2 million over the next 9 years.
Although there are no published studies on the cost-effectiveness of ART from the Caribbean, several studies have examined the cost-effectiveness of ART in other resource-limited settings.15,38-40 Goldie et al15 reported cost-effectiveness for ART treatment in Côte d'Ivoire that ranged from very cost-effective (less than the GDP) to cost-effective (<3 times the GDP). Two studies from South Africa reported incremental cost-effectiveness ratios that ranged from cost-effective at current ART prices to cost saving at anticipated reduced ART prices.38,39 Paton et al40 reported cost-effectiveness for treatment in Singapore, finding that ART was cost-effective across all stages of HIV infection. The results of the current analysis are consistent with these findings from Africa and Asia.
In March 2005, funding from the Global Fund to Fight AIDS, Tuberculosis, and Malaria began a 5-year effort to develop structure and capacity for treatment of HIV in the OECS, with a project budget of $8.9 million.1,41 According to the current study, although the 1-year cost for providing medical care and drugs to all currently identified HIV-infected persons in the OECS is $685,500, the cost to provide services over the lifetimes of these persons is between $9.9 and $18.2 million over the next 9 years, depending on the price of second-line ART. These forecasted costs do not include costs required to achieve other regional aims, including the expansion of voluntary counseling and testing; capacity for local laboratory monitoring; and capacity building, including infrastructure, new systems, and personnel training or resources needed for newly identified patients through expanded testing. Therefore, this study suggests that although implementation of universal access to treatment for currently identified patients in the OECS may be initiated with current support from the Global Fund to Fight AIDS, Tuberculosis, and Malaria, additional funding is required to sustain lifetime care for currently infected persons. Reducing the cost of second-line ART to the region would substantially lower overall expenditures required to provide universal access to treatment in the OECS.
This analysis has several limitations. There remains a dearth of region-specific data from the Caribbean, especially on CD4 cell counts, HIV RNA levels, and other markers of HIV natural history. Therefore, data for this study were derived from multiple sources. Because of the lack of complete OECS data, including data on short-term mortality from opportunistic diseases and chronic mortality, we calibrated the chronic mortality rate in the model to Jamaican national surveillance data.17 Although the calibrated chronic mortality is quite high compared with mortality in the MACS, this rate may include increased death from opportunistic diseases in the OECS as well as other AIDS-related deaths. Although better estimates for these parameters would give more specific projections for survival and cost-effectiveness, we dealt with the lack of primary data through calibration and sensitivity analyses, finding that the policy conclusions remained robust across a wide range of estimates. It was similarly difficult to find high-quality data on the prevalence of HIV infection in the region and the proportion of those infected who require treatment. The most recently reported results were used; however, as better estimates become available, the lifetime cost results of the current study can be applied to update the budgetary analysis for the region. Finally, the budgetary projections did not account for costs arising from the treatment and care of incident HIV cases, because the model used was not an epidemic model.
Most patients in the Barbados cohort, from which we derived first-line ART efficacy, were initiated on an efavirenz-based regimen with 2 nucleoside reverse transcriptase inhibitors.25,26 Although the current standard of care for first-line ART in the OECS is a nevirapine-based regimen, there is evidence of similar efficacy using either of these NNRTIs.42 Therefore, we applied the efficacy estimate from Barbados, coupled with nevirapine cost, which is used in most cases in the OECS, for the base case. Further, the percentage of patients suppressed in the Barbados cohort was similar to that in other studies, including the Antiretroviral Therapy in Lower Income Countries Collaboration (ART-LINC), the Haitian Study Group for Kaposi's Sarcoma and Opportunistic Infections, and the Médecins Sans Frontières Khayelitsha, South Africa cohort.23,43-45
Much attention has been given to the HIV epidemic in the Caribbean, yet few epidemiologic and clinical research studies have been published from the region, and most of those are from Haiti.23,46 Furthermore, there is a lack of operational and policy research to inform efficient regional HIV policy formation. The compilation of available region-specific data inputs for this analysis highlights the need for increased research in the Caribbean to understand better the natural history of HIV disease, the efficacy of prophylaxis and ART, and the impact on quality of life of HIV disease and its treatment. This analysis shows that the current cost of second-line ART is extremely high and strongly influences the cost-effectiveness and total lifetime cost of adequate HIV care in the Caribbean. Even if currently reported generic drug prices could be obtained in the region, the cost of second-line drugs remains a major component of total costs and may ultimately limit access to effective treatment. Lower drug prices are needed for second-line therapy. At the same time, national programs should distribute less expensive first-line therapy to all who need it and work to increase total funding for treatment in the region, which is going to be required in the near future. The budgetary impact of second-line ART highlights the critical importance of adherence support programs, because maximizing the effectiveness of first-line ART regimens should contribute to sustainable HIV treatment programs. ART for HIV disease in the Caribbean is cost-effective and can be further optimized by obtaining lower cost second-line therapy to make the best use of available resources.
The authors gratefully acknowledge Francis Burnett of the OECS Pharmaceutical Procurement Service for providing current regional drug costs, Dr. Peter Figureoa and the HIV/AIDS surveillance team of the Jamaican Ministry of Health for providing access to surveillance data, and the entire CEPAC team for providing contributions to the analysis and interpretation of data.
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