Quality of life outcomes of saquinavir, zalcitabine and combination saquinavir plus zalcitabine therapy for adults with advanced HIV infection with CD4 counts between 50 and 300 cells/mm³

Background: Benefits in patient health-related quality of life (HRQL) have not yet been demonstrated for combination antiretroviral therapy with protease inhibitors and nucleoside analogues. This double-blind study evaluated zalcitabine or saquinavir monotherapy and combination saquinavir plus zalcitabine therapy on HRQL of human immunodeficiency virus (HIV)-infected adults. Methods: 940 HIV-infected patients (CD4 counts 50-300 cells/mm³) who had discontinued zidovudine therapy (for intolerance or treatment failure) were randomized to one of three regimens: zalcitabine 0.75 mg every 8 h; saquinavir 600 mg every 8 h; or combination zalcitabine 0.75 mg plus saquinavir 600 mg every 8 hours. HRQL was measured at baseline, 24 and 48 weeks using the Medical Outcome Study HIV Health Survey (MOS-HIV). The primary endpoints were the physical and mental health summary scores (PHS; MHS) of the MOS-HIV as well as a global visual analogue scale (VAS) score. Results: After 24 weeks, the zalcitabine-treated patients demonstrated significantly greater decreases in PHS scores (-4.4 ± 0.6; saquinavir: -1.3 ± 0.6; zalcitabine plus saquinavir: -1.7 ± 0.6; P < 0.0001) and MHS scores (-2.2 ± 0.5; saquinavir: -1.0 ± 0.5; zalcitabine plus saquinavir: -0.5 ± 0.5; P = 0.032) compared to saquinavir and zalcitabine plus saquinavir treated patients. No differences were observed on the VAS (P = 0.172). Nine of 10 MOS-HIV subscales demonstrated results consistent with the primary endpoints. After 48 weeks, a statistically significant difference between the saquinavir-treated groups and the zalcitabine monotherapy group was observed for PHS scores (zalcitabine: -5.8 ± 0.6; saquinavir: -4.1 ± 0.6; zalcitabine plus saquinavir: -3.5 ± 0.6; P = 0.014). Conclusions: Saquinavir monotherapy and combination saquinavir plus zalcitabine demonstrated a benefit in HRQL relative to zalcitabine monotherapy in patients with prior zidovudine therapy. The HRQL findings are concordant with improved survival and reduced clinical progression of HIV infection found in this study.