Cost-effectiveness of newer antiretroviral drugs in treatment-experienced patients with multidrug-resistant HIV disease

Abstract

Objective: Newer antiretroviral drugs provide substantial benefits but are expensive. The cost-effectiveness of using antiretroviral drugs in combination for patients with multidrug-resistant HIV disease was determined.

Design: A cohort state-transition model was built representing treatment-experienced patients with low CD4 counts, high viral load levels, and multidrug-resistant virus. The effectiveness of newer drugs (those approved in 2005 or later) was estimated from published randomized trials. Other parameters were estimated from a randomized trial and from the literature. The model had a lifetime time horizon and used the perspective of an ideal insurer in the United States. The interventions were combination antiretroviral therapy, consisting of 2 newer drugs and 1 conventional drug, compared with 3 conventional drugs. Outcome measures were life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness.

Results: Substituting newer antiretroviral drugs increased expected survival by 3.9 years in advanced HIV disease. The incremental cost-effectiveness ratio of newer, compared with conventional, antiretroviral drugs was $75,556/QALY gained. Sensitivity analyses showed that substituting only one newer antiretroviral drug cost $54,559 to $68,732/QALY, depending on assumptions about efficacy. Substituting 3 newer drugs cost $105,956 to $117,477/QALY. Cost-effectiveness ratios were higher if conventional drugs were not discontinued.

Conclusions: In treatment-experienced patients with advanced HIV disease, use of newer antiretroviral agents can be cost-effective, given a cost-effectiveness threshold in the range of $50,000 to $75,000 per QALY gained. Newer antiretroviral agents should be used in carefully selected patients for whom less expensive options are clearly inferior.

Figure 1. Calibration of Model Outputs to OPTIMA data

Comparison of outcomes observed in the OPTIMA model (dark solid line) and those predicted by the simulation model using conventional antiretroviral drugs approved before 2005 (light dotted line). Observed curves are Kaplan-Meier plots. The top panel illustrates the time to death and the bottom panel the time to first AIDS-defining illness or death.

Figure 2. Costs and Quality-adjusted Survival Associated with Substituting Newer for Conventional Antiretroviral Drugs

Each point in the curve represents a distinct strategy, either treatment with conventional antiretroviral drugs or addition of newer antiretroviral drugs combined with withdrawal of an equal number of conventional drugs. Each additional drug is assumed to increase the odds of suppression 2-fold. The baseline estimate is assumed to apply to the situation in which 2 drugs are substituted. The slope of each line yields the incremental cost-effectiveness of each strategy relative to the next least expensive (boxes).

Figure 3. Sensitivity to Virologic Efficacy and Intolerance of Newer Antiretroviral Therapy

Sensitivity analysis of the odds ratio of achieving virologic suppression under assumptions of high discontinuation (49%, equal to conventional therapy, solid line) or low discontinuation (24.5%, dashed line) of newer antiretroviral drug therapies. The vertical line represents the base case estimate of the odds ratio and the shaded box represents the range of the 95% confidence interval (Supplementary Digital Content).