Compared with the current standard of care, a strategy of regimen simplification with boosted PI therapy is associated with an increased duration of survival, as long as PI resistance does not develop. Simplification regimen recipients who do not develop PI resistance have an undiscounted life expectancy of 27.9 years, compared with 27.1 years for standard-of-care subjects (). Discounted QALE for the simplification regimen subjects is 14.9 years, compared with 14.7 years for patients receiving the standard-of-care regimen. However, simplification strategy subjects who have developed PI resistance at the time of simplification regimen failure have an undiscounted life expectancy of 26.5 years and a QALE of 14.5 years. These values are shorter than the values for subjects receiving the standard of care. For an entire population, the expected QALE of the simplification strategy remains higher than that for the standard-of-care strategy, even when a large proportion of simplification strategy subjects develop PI resistance at the time of virologic failure. In the base case (in which 83% of subjects have a suppressed HIV RNA level at 48 weeks while receiving the simplification regimen), 56% of those who experience virologic failure can develop PI resistance before the QALE of the simplification strategy becomes less than that for the standard-of-care strategy.
Life expectancy and lifetime costs.
Simplification strategy subjects who do not develop PI resistance at the time of virologic failure are projected to live longer than subjects receiving the standard of care, because they receive an additional line of therapy without compromising future treatment options. Standard-of-care strategy subjects spend a mean of 6.7 discounted quality-adjusted life years (QA-LYs) receiving their first line of therapy (i.e., an NNRTI-based regimen) and 2.8 QALYs receiving their second line of therapy (a boosted PI plus NRTIs), for a total of 9.5 QALYs (). This represents a mean undiscounted total time receiving these regimens of 14.2 years. Simplification strategy subjects who do not develop PI resistance spend an average of 10.7 QALYs receiving 3 similarly effective regimens: atazanavir-ritonavir alone (5.8 QALYs), atazanavir-ritonavir with NRTIs (3.0 QALYs), and an NNRTI-based regimen (1.8 QALYs). This represents a mean undiscounted total time receiving these regimens of 16.7 years.
Figure 1 Discounted quality-adjusted life expectancy, by treatment strategy. ATV/r, atazanivir-ritonavir; DRV/r, darunavir-ritonavir; ENF, enfuvirtide; LPV/r, lopinavir-ritonavir; NNRTI, nonnucleoside reverse-transcriptase inhibitor; NRTI, nucleoside reverse-transcriptase (more ...)
We conducted sensitivity analyses that changed both the efficacy of the atazanavir-ritonavir regimen and the CD4 cell count distribution at entry into the analysis (). In the worst-case scenario, with the lowest virologic suppression rate and mean baseline CD4 cell count (i.e., 75% of patients have an HIV RNA level < 400 copies/mL at 48 weeks and with a mean CD4 cell count of 475 cells/μL at cohort entry), the QALE of subjects receiving the simplification strategy is 14.3 QALYs for those who have not developed PI resistance at the time of failure of the first regimen and 13.9 QALYs for those who have developed PI resistance, compared with 14.2 QALYs for subjects receiving the standard of care. The break-even percentage of subjects receiving the simplification strategy who can develop PI resistance decreases to 33%. In contrast, with a 90% virologic suppression rate at 48 weeks and a mean baseline CD4 cell count of 575 cells/μL, 92% of simplification strategy subjects would need to develop PI resistance before QALE would be lower for the simplification group. In this scenario, subjects undergoing the standard of care spend more time receiving regimens with lipoatrophy and neuropathy, resulting in greater quality-of-life decrements of treatment. Their slightly longer life expectancy, compared with simplification regimen subjects who develop resistance, is offset by greater reductions in quality of life associated with treatment-related adverse effects. When the efficacy of the atazanavir-ritonavir regimen with NRTIs is improved, the break-even percentages are 28% in the base case, 22% with a mean CD4 cell count of 475 cells/μL at cohort entry, and 38% with a mean CD4 cell count of 575 cells/μL at cohort entry.
Figure 2 “Break-even” proportion of subjects with HIV with protease inhibitor (PI) resistance after failure of a simplification regimen that would result in a quality-adjusted life expectancy equivalent to that of the standard of care (see Results). (more ...)
We conducted several sensitivity analyses that varied the toxicity benefit of the simplification strategy (). When toxicities are decreased by 50%, the QALE for subjects receiving the simplification strategy becomes 14.9 years for those who do not develop resistance and 14.6 years for those who develop resistance, compared with 14.8 years for subjects receiving the standard of care; the break-even threshold becomes 38%. When we ignore the toxicity benefit altogether, the break-even threshold becomes 26%; if the rate of toxicities is increased by 50%, the break-even threshold becomes 71%. If we assume the quality-of-life effects of lipoatrophy and neuropathy continue for life, the break-even percentage becomes 86%.
Average discounted lifetime costs for all patients receiving the simplification strategy, including those who develop PI resistance, are lower than for patients receiving the standard of care. The average discounted lifetime cost for simplification strategy subjects is $430,200 for those who do not develop PI resistance and $384,300 for those who develop PI resistance, compared with $456,700 for standard-of-care strategy subjects (). The average undiscounted annual cost for simplification strategy subjects without resistance ($26,200) or with resistance ($24,400) is lower than for standard-of-care subjects ($28,100), and this occurs consistently ().
Average undiscounted annual cost per patient, by treatment strategy, in 2005 US dollars. ATV/r, atazanavir-ritonavir.
If HIV RNA testing is conducted monthly (instead of every 3 months) during the first 6 months of simplified maintenance therapy, the discounted lifetime cost is $430,600 for subjects who do not develop resistance and $384,800 for subjects who do develop resistance, compared with $456,700 for subjects receiving the standard of care. If monthly HIV RNA testing continues for the duration of the simplification regimen, the cost of the simplification strategy remains lower for subjects without resistance ($436,700) and subjects with resistance ($390,900). When the cost of atazanavir-ritonavir is lowered to equal that of lopinavir-ritonavir, the discounted lifetime cost is $379,400 for subjects who do not develop resistance and $350,700 for subjects who develop resistance, compared with $440,500 for subjects receiving the standard of care.
In the scenario in which a hypothetical regimen containing an integrase inhibitor is added to each strategy, undiscounted life expectancy increases by 1.0–1.3 years. The break-even threshold is 39%, and the average discounted lifetime costs for simplification strategy subjects who do or do not develop PI resistance remain lower than the cost for standard-of-care strategy subjects.