IMPROVED SURVIVAL AND REDUCED CLINICAL PROGRESSION IN HIV-INFECTED PATIENTS WITH ADVANCED DISEASE TREATED WITH SAQUINAVIR PLUS ZALCITABINE

The objective of this randomized, double-blind, controlled multicentre study was to evaluate the efficacy of saquinavir alone or in combinat ion with zalcitabine compared to zalcitabine monotherapy in reducing p rogression of human immunodeficiency virus (HIV) disease. Nine hundred and forty HIV-infected patients with more than 16 weeks of prior zido vudine therapy and pre-study entry CD4 cell counts between 50 and 300 cells/mm(3) were randomized to saquinavir 600 mg every 8 h, zalcitabin e 0.75 mg every 8 h or the combination of both drugs. In an intent-to- treat analysis, the treatment arms were balanced with respect to demog raphics, baseline HIV RNA (mean 5.0 log(10) copies/ml) and CD4 lymphoc yte count (mean 170 cells/mm(3)). More patients in the zalcitabine arm stopped therapy because of toxicity than in the other two arms (25% v ersus 16%; P=0.005). Peripheral neuropathy was the most common treatme nt-limiting toxicity. Fifty-one patients in the saquinavir plus zalcit abine group developed an AIDS-defining event or died compared to 84 an d 88 in the saquinavir and zalcitabine monotherapy groups respectively ; Combination treatment with saquinavir plus zalcitabine reduced the r isk of progression to AIDS by 49% (95% confidence interval 0.36 to 0.7 2, P=0.0001) and reduced death by 68% (95% confidence interval 0.16 to 0.64, P=0.001) compared to zalcitabine monotherapy. The addition of s aquinavir to zalcitabine resulted in a significant reduction in progre ssion to AIDS or death compared with zalcitabine alone.