Cost-effectiveness of antiretroviral regimens in the World Health Organization's treatment guidelines: a South African analysis

Abstract

Objective: the World Health Organization (WHO) recently changed its first-line antiretroviral treatment guidelines in resource-limited settings. The cost-effectiveness of the new guidelines is unknown.

Design: comparative effectiveness and cost-effectiveness analysis using a model of HIV disease progression and treatment.

Methods: using a simulation of HIV disease and treatment in South Africa, we compared the life expectancy, quality-adjusted life expectancy, lifetime costs, and cost-effectiveness of five initial regimens. Four are currently recommended by the WHO: tenofovir/lamivudine/efavirenz; tenofovir/lamivudine/nevirapine; zidovudine/lamivudine/efavirenz; and zidovudine/lamivudine/nevirapine. The fifth is the most common regimen in current use: stavudine/lamivudine/nevirapine. Virologic suppression and toxicities determine regimen effectiveness and cost-effectiveness.

Results: choice of first-line regimen is associated with a difference of nearly 12 months of quality-adjusted life expectancy, from 135.2 months (tenofovir/lamivudine/efavirenz) to 123.7 months (stavudine/lamivudine/nevirapine). Stavudine/lamivudine/nevirapine is more costly and less effective than zidovudine/lamivudine/nevirapine. Initiating treatment with a regimen containing tenofovir/lamivudine/nevirapine is associated with an incremental cost-effectiveness ratio of $1045 per quality-adjusted life year compared with zidovudine/lamivudine/nevirapine. Using tenofovir/lamivudine/efavirenz was associated with the highest survival, fewest opportunistic diseases, lowest rate of regimen substitution, and an incremental cost-effectiveness ratio of $5949 per quality-adjusted life year gained compared with tenofovir/lamivudine/nevirapine. Zidovudine/lamivudine/efavirenz was more costly and less effective than tenofovir/lamivudine/nevirapine. Results were sensitive to the rates of toxicities and the disutility associated with each toxicity.

Conclusion: among the options recommended by WHO, we estimate only three should be considered under normal circumstances. Choice among those depends on available resources and willingness to pay. Stavudine/lamivudine/nevirapine is associated with the poorest quality-adjusted survival and higher costs than zidovudine/lamivudine/nevirapine.

Figure 1. Study regimens with associated toxicities and regimen substitutions

The five first-line strategies evaluated in this study are shown with each of the associated toxicities we evaluated. Toxicities resulted in a substitution to another 1^st line regimen, if another regimen is thought to have a superior toxicity profile. The rates of toxicities and virologic failure of each regimen are shown in Table 1.

Figure 2. Health and Cost Outcomes for First-line Antiretroviral Strategies

Lifetime discounted costs in 2009 US dollars and quality-adjusted life expectancy for the five first-line antiretroviral regimens. Strategies that could be considered cost-effective are connected with a line that indicates the incremental cost-effectiveness ration of moving from one strategy to the next. Two strategies – stavudine/lamivudine/nevirapine and zidovudine/lamivudine/efavirenz – are unlikely to be cost effective. The results support the decision to exclude stavudine/lamivudine/nevirapine from the list of recommended regimens, and suggest an important role for tenofovir-based regimens.

Figure 3. Results of a Probabilistic Sensitivity Analysis

This presents the results of repeated simulations allowing for simultaneous uncertainty in all model parameters. The small markers represent the results of individual simulations, while the large central markers represent the results from the primary analysis. The figure shows the dominance of zidovudine/lamivudine/nevirapine over stavudine/lamivudine/nevirapine is less certain than the other comparative results.

Figure 1. Model flow of routine patient care management

Squares represent states or processes, and diamonds represent decision nodes. For example, newly diagnosed HIV+ patients are seen in clinic, and evaluated whether they meet criteria to start ART. If they meet criteria, they are started on first-line ART, and if they do not meet criteria, the model evaluates them again next month. The model does not show the development of acute clinical events such as severe opportunistic diseases or some medication toxicities, which may occur at any time.