617    

Background:  Improving or preserving health-related quality of life is an increasingly important goal in the treatment of HIV. We compared the effect of tipranavir vs comparator regimens on health-related quality of life in 2 randomized clinical trials for ARV-experienced patients with AIDS.

Methods:  Patients were enrolled in 2 multinational phase III randomized open-label clinical trials in North American and Australia (RESIST-1), and Europe and Latin America (RESIST-2). Data are from the planned 24-week interim analyses. Tipranavir 500 mg twice daily boosted with ritonavir 200 mg twice daily (TPV/r) was evaluated vs boosted comparator protease inhibitor (CPI/r) regimens selected based on genotype and treatment history. All patients received an optimized background regimen. Eligible patients had received prior nuclease reverse transcription inhibitors (NRTI), non-nuclease reverse transcription inhibitors (NNRTI), and at least 2 different protease inhibitors (PI); had 1 or 2 primary PI-resistance mutations; and HIV RNA ≥ 1000 copies/mm³. Health-related quality of life was assessed at weeks 8, 16, and 24 using the 35-item MOS-HIV, translated and validated in the relevant languages. Analyses included all randomized patients who had received at least 1 dose of study drug and completed at least 1 survey. The primary outcome was change from baseline to 24 weeks in the physical health and mental summary scores. Exploratory analyses examined subscale scores. Multivariable longitudinal analyses used GEE modeling to explore treatment effects across all time points.

Results:  A total of 620 and 494 patients were included in RESIST-1 and RESIST-2. Patients on CPI/r were more likely to be lost to follow-up at all time-points after baseline (at 24 weeks:  RESIST-1, 46 vs 15%; RESIST-2, 66 vs 43%). Larger differences between groups were observed in RESIST-2 compared with RESIST-1. In RESIST-2, at week 8 patients on TPV/r reported improvements in all MOS-HIV dimensions, with differences in change scores of 7.6 points for pain, 4.1 for cognitive functioning, and 1.9 for physical health score (p all < 0.05). At week 24, TPV/r patients had significantly larger changes in general health (6.2) and mental health score (3.6). Using GEE, there was a non-significant trend favoring TPV/r. In RESIST-1, non-significant trends generally favored TPV/r. Differential loss to follow-up raises the possibility that scores for the CPI/r arm may have been overestimated.

Conclusions:  The results from this sample of ARV experienced patients suggest that TPV/r does not adversely affect HEALTH-RELATED QUALITY OF LIFE . The impact of TPV/r on quality of life was at least as positive as that with comparator agents.

Keywords: quality of life; tipranavir; clinical trial