When we assumed US$ 1438 for monthly HAART costs, the scale of cumulative net benefit was reduced, reaching a plateau of approximately US$ 760 million over 30 years. However, a similar pattern of cost-effectiveness was observed, with the HAART expansion scenario reaching cost-effectiveness within 7 years and remaining cost-effective throughout the 30-year duration of simulated time.
The overall population and patient-centered incremental net benefits are shown in Fig. 3. For the first 5 years of expanded HAART, it is estimated that overall population net benefit is comprised largely of net benefits accrued by the initial group of individuals infected at baseline. The general trend continues for approximately 10 years, with the overall population net benefits gradually increasing beyond the patient-centered net benefits. After 10 years, there is a widening divergence, with overall population net benefits increasingly explained by averted infections. After 30 years, patient-centered net benefits account for approximately half of overall population net benefits.
In this study, we demonstrated the potential cost-effectiveness of expanding the use of HAART – as defined by increasing the proportion of HIV-infected individuals with CD4 cell counts below 350 cells/μl receiving HAART from 50 to 75% – in British Columbia. Increased treatment was found to reduce the incidence of new infections and, despite the up-front acquisition costs associated with an increase in HAART use, the strategy was estimated to become cost-effective within 4 years.
Several other mathematical models have been used to assess the impact of HAART on HIV transmission. Relative to the results presented here, some models have resulted in similar or more dramatic effects on HIV incidence [15,26,36], whereas others have resulted in more conservative estimates [37,38]. All investigators have reported some reduction in the incidence of new infections when treatment rates are increased. Differences across studies are due in part to varying assumptions regarding the impact of HAART on infectivity, although when evaluating infectious disease prevention strategies, the current phase of the particular epidemic being modeled is an important factor , so some discordance between studies undertaken in different settings is to be expected. To our knowledge, ours is the first study to incorporate a comprehensive economic evaluation in this context.
The microsimulation component of the model, which described the clinical course and economic implications of HIV disease, was based on high-quality population-based data for British Columbia and is thus expected to be accurate for British Columbia and other areas with similar healthcare systems. Because this component of the model was based on observational data, it describes actual clinical and virological outcomes observed in practice, rather than idealized outcomes based on the assumption of optimal medication adherence. Comprehensive direct medical costs were available so that costs associated with treating HIV symptoms, HAART toxicity, and background medical issues were included.
The model addressed multiple sources of complexity of HIV disease through the integration of microsimulation and transmission models. Because HIV is an infectious disease, a dynamic modeling method, such as the transmission model used here, is required to quantify the impact of a prevention program. Due to the relatively long clinical course of HIV, it also displays properties of a chronic disease, and lifetime direct medical costs may vary substantially across individuals. Microsimulation methods based on statistical models have been well developed within the health economics literature for describing the costs associated with a chronic disease . Microsimulation methods provide a framework for quantifying the impact of HAART use at the individual level. By combining the two modeling techniques, we were able to exploit the strengths of two complementary methods: one for addressing the infectious nature of HIV transmission and the other for addressing the chronic nature and individual-level variability associated with HIV clinical processes and medical costs.
A limitation of the study was the paucity of data available for assigning parameters to the disease-transmission component of the model. Parameters for which limited empirical data were available were based on a combination of expert opinion and calibration to historical incidence and treatment rates . We allowed parameters to vary across a relatively wide range of plausible values in the probabilistic sensitivity analysis (Appendix Table A1, http://links.lww.com/QAD/A53). The results of this sensitivity analysis were consistent with the base-case analysis regarding cost-effectiveness over time.
When considering a 30-year time horizon, long-term changes in diagnostics, treatment options, clinical indication for treatment initiation, and treatment costs may influence the future cost-effectiveness profile. Although some medication costs may decrease as product patents expire, there is also the possibility for more efficacious and more costly medications to be brought to market. The results reported here do not reflect any such hypothetical changes. Under the assumption that a favorable economic profile would be required for any future guideline changes to be made, it is not expected that they would prevent the proposed intervention of increasing HAART from achieving a positive incremental net benefit within a time frame similar to that reported here.
In order to not overestimate the net benefit associated with the HAART expansion scenario, wherever possible, we made conservative assumptions to make increased uptake of HAART appear less effective. A recent meta-analysis provides data that suggest that the impact of reduced viral load on infectivity may be larger than the figures used here , particularly at very low levels of viral load . We chose to use the more conservative figure to be certain that the impact was not overestimated. We also made the conservative choice of 0.87 as the utility value associated with individuals susceptible for HIV infection, equivalent to the highest utility reported for individuals infected with HIV . Choosing the lowest plausible utility value for susceptible individuals biases results against a prevention program. In addition, for all parameters related to primary infection, we assumed values on the upper end of the plausible range. We assumed that the phase would last 60 days, that viral load would remain at 6 log-copies/ml throughout the phase, and that there would be no decrease in risk behavior. Transmission during the primary phase was assumed to be unaffected by the program to increase uptake of HAART.
The incremental net benefit we calculated was based on a payer perspective. Taking a societal perspective and including indirect costs, although outside the scope of this study, would likely yield a higher incremental net benefit associated with HAART expansion. Indirect costs are those borne to society when individuals who would otherwise be able to work cannot due to illness or death. In the United States, the indirect costs associated with HIV have been estimated to be substantially higher than the direct costs . The HAART expansion scenario was associated with improved health among individuals currently infected with HIV as well as reduced transmission of new infections, both of which would reduce the burden of indirect costs and increase the incremental net benefit.
In this study, we described a methodology for evaluating a preventive intervention for an infectious disease with a lengthy clinical course, providing a framework that could potentially be used in other similar applications. On the basis of this methodology, an intervention to increase the HAART treatment rate from 50 to 75% of HIV-infected individuals with CD4 cell count below 350 cells/μl in British Columbia was demonstrated to be a cost-effective strategy. This result was obtained under several conservative assumptions that were chosen to bias results against the intervention. Due to these assumptions, it is plausible that the actual net benefit associated with the intervention is even higher than that reported here. These cost-effectiveness results are consistent with public health objectives: all individuals who are eligible for an established life-saving treatment should receive it.
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