THRESHOLDS FOR COST-EFFECTIVENESS OF ADDING AN AGENT THAT IMPROVES IMMUNE RESPONSES TO INITIAL ANTIRETROVIRAL THERAPY (ART) IN HIV-INFECTED PATIENTS: GUIDANCE FOR DRUG DEVELOPMENT

Purpose: The strategy of adding an immune-enhancing drug to stable ART in HIV-infected patients with suboptimal immune reconstitution has been investigated without success. An alternative strategy being considered is to incorporate such an enhancer into initial ART. We evaluated the threshold clinical benefits and cost that would be required for such a strategy to have a cost-effectiveness ratio <$100,000/QALY in the US.

Method: We used a widely-published Monte Carlo simulation of HIV disease progression and treatment in the US (the CEPAC model) to compare initial ART with or without a drug that could potentially improve immune reconstitution (CD4 cell response) in the first 6 months after treatment initiation. In the base case, patients had mean CD4 175 cells/µl, and the 6-month additional cost was $10,560 based on the cost of a drug currently under investigation (maraviroc).  Immune-enhanced ART benefit was modeled as a 10-50% increase over a mean 116 CD4 cell gain in the first 6 months with standard ART and we assumed the additional CD4 cell increase would have clinical benefit. Outcomes include life expectancy and cost-effectiveness in $US/QALY. Costs and QALYs were discounted at 3%/year. Treatment costs and mean CD4 cells at ART initiation were varied in sensitivity analyses.  

Result: Immune-enhanced ART with an additional 10% increase in CD4 cell count over 6 months yields a projected life expectancy increase of 1.6 months compared to standard ART with a cost-effectiveness ratio of $149,000/QALY. To achieve a cost-effectiveness ratio <$100,000/QALY (see Figure), CD4 cell count improvement must be >20% (solid diamond) or cost must be at least 40% lower (open circle) than the base case.  For patients with lower CD4 cells (mean CD4 75/µl at ART initiation), the CD4 count improvement must be >30% or cost must be at least 50% lower.

                 

     

 

Conclusion: Immune-enhanced therapies added to first-line ART have the potential to improve life expectancy. For such an intervention to be cost-effective, however, it needs to provide >20% improvement in immune reconstitution or cost substantially less than drugs currently being evaluated.