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/mm(3)

Background: Benefits in patient health-related quality of life (HRQL) have not yet been demonstrated for combination antiretroviral therapy with prote ase inhibitors and nucleoside analogues. This double-blind study evaluated zalcitabine or saquinavir monotherapy and combination saquinavir plus zalci tabine therapy on HRQL of human immunodeficiency virus (HIV)-infected adult s. Methods: 940 HIV-infected patients (CD4 counts 50-300 cells/mm(3)) who had discontinued zidovudine therapy (for intolerance or treatment failure) were randomized to one of three regimens: zalcitabine 0.75 mg every 8 h; saquin avir 600 mg every 8 h; or combination zalcitabine 0.75 mg plus saquinavir 6 00 mg every 8 hours. HRQL was measured at baseline, 24 and 48 weeks using t he Medical Outcome Study HIV Health Survey (MOS-HIV). The primary endpoints were the physical and mental health summary scores (PHS; MHS) of the MOS-H IV as well as a global visual analogue scale (VAS) score. Results: After 24 weeks, the zalcitabine-treated patients demonstrated sign ificantly 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 patien ts. No differences were observed on the VAS (P=0.172). Nine of 10 MOS-HIV s ubscales demonstrated results consistent with the primary endpoints. After 48 weeks, a statistically significant difference between the saquinavir-tre ated groups and the zalcitabine monotherapy group was observed for PHS scor es (zalcitabine: -5.8+/-0.6: saquinavir: -4.1+/-0.6; zalcitabine -3.5+/-0.6 ; P=0.014). Conclusions: Saquinavir monotherapy and combination saquinavir plus zalcita bine demonstrated a benefit in HRQL relative to zalcitabine monotherapy in patients with prior zidovudine therapy. The HRQL findings are concordant wi th improved survival and reduced clinical progression of HIV infection foun d in this study.