Comparator Protease Inhibitor Research Articles

Cost-effectiveness of Tipranavir in Treatment-Experienced HIV Patients in the United States

Objective: To compare the estimated long-term outcomes, costs, and cost-effectiveness of tipranavir boosted with ritonavir (TPV/r) versus investigator-selected ritonavir-boosted comparator protease inhibitor (CPI/r) using the observed 48-week data from the RESIST trials in a previously published Markov model. Method: A previously developed 3-stage Markov model was modified to reflect US practice patterns for treatment-experienced HIV patients using 2007 costs and combined phase III tipranavir trial data (RESIST-1 and -2). The 12 model health states were defined by CD4 cell count and viral load that have previously been identified as predictors of HIV/AIDS progression. Resource use and quality of life weights were linked to each health state. Disease progression beyond the 48-week trial period was based on HAART treatment-experienced patients from data collected by the University of South Carolina. Costs were estimated from the payer perspective. Results: TPV/r patients remained longer in health states defined by higher CD4 cell count and lower viral load compared to CPI/r patients. This reduced the rate of AIDS-defining events by 12.35% over 5 years and resulted in 0.64 quality-adjusted life-years (QALYs) gained (discounted at 3%) over the model time horizon (remaining lifetime). The incremental cost-effectiveness ratio (ICER) of TPV/r versus CPI/r was $56,517/QALY (discounted at 3%). Excluding patients also treated with enfuvirtide reduced the ICER to $46,147/QALY. Conclusion: TPVI/r is cost-effective in the United States compared to CPI/r in treatment-experienced HIV-1—infected patients.

Efficacy of the Protease Inhibitors Tipranavir plus Ritonavir in Treatment-Experienced Patients: 24-Week Analysis from the RESIST-1 Trial

Improved treatment options are needed for patients infected with multidrug-resistant human immunodeficiency virus type 1 (HIV-1). The nonpeptidic protease inhibitor tipranavir has demonstrated antiviral activity against many protease inhibitor-resistant HIV-1 isolates. The Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST-1) trial is an ongoing, open-label study comparing the efficacy and safety of ritonavir-boosted tipranavir (TPV/r) with an investigator-selected ritonavir-boosted comparator protease inhibitor (CPI/r) in treatment-experienced, HIV-1-infected patients. Six hundred twenty antiretroviral-experienced patients were treated at 125 sites in North America and Australia. Before randomization, all patients underwent genotypic resistance testing, which investigators used to select a CPI/r and an optimized background regimen. Patients were randomized to receive TPV/r or CPI/r and were stratified on the basis of preselected protease inhibitor and enfuvirtide use. Treatment response was defined as a confirmed reduction in the HIV-1 load of > or = 1 log10 less than the baseline level without treatment change at week 24. Mean baseline HIV-1 loads and CD4+ cell counts were 4.74 log10 copies/mL and 164 cells/mm3, respectively. At week 24, a total of 41.5% of patients in the TPV/r arm and 22.3% in the CPI/r arm had a > or = 1-log10 reduction in the HIV-1 load (intent-to-treat population; P<.0001). Mean increases in the CD4+ cell count of 54 and 24 cells/mm3 occurred in the TPV/r and CPI/r groups, respectively. Adverse events were slightly more common in the TPV/r group and included diarrhea, nausea, and vomiting. Elevations in alanine and aspartate aminotransferase levels and in cholesterol/triglyceride levels were more frequent in the TPV/r group. TPV/r demonstrated superior antiviral activity, compared with investigator-selected, ritonavir-boosted protease inhibitors, at week 24 in treatment-experienced patients with multidrug-resistant HIV-1 infection.