ACTG 229 compared the three drug combination of Saquinavir (formerly Ro 31-8959), zalcitabine (ddC) and zidovudine (ZDV) to the two-drug combination of saquinavir and ZDV and the two-drug combination of ddC and ZDV. The 302 patients on the study had CD4 counts between 50 and 300 and had received prior ZDV therapy for at least four months. The trial was double-blind and patients were treated for 24 weeks. The dose of saquinavir 600 mg tid, and the dose of ddC was .75 mg tid. ZDV at 200 mg tid was given as an open label medication to all patients. The principal measures of efficacy were increases in CD4 lymphocyte counts and drops in viremia measured by HIV PBMC co-culture.
The rate of increase of CD4 counts was greater in patients receiving the triple combination (n=96) than that of ddC/ZDV (n=100) (p=0.001) and that of saquinavir/ZDV (n=98) (p=0.08). The normalized area under the CD4 curve was greater with the triple combination than with either saquinavir/ZDV (n=98) (p=0.03) or ddC/ZDV (p<0.001). At 24 weeks, 31% of the patients on the triple combination had CD4 counts which had returned to baseline as compared to 37% on saquinavir/ZDV and 55 % on ddC/ZDV. The results of HIV PBMC co-culture demonstrated that the triple combination produced significantly greater reductions in viral burden than either of the other arms.
There were no major differences in the toxicities noted on the three treatments. Eleven patients had a major clinical event (new AIDS-defining opportunistic infection or death) on the study. One patient was on the triple combination, six were on saquinavir/ZDV and four were on ddC/ZDV (p=0.18). There were two deaths on the study during the first 24 weeks, both occurring on the saquinavir/ZDV arm, and both attributed to brain masses.
In conclusion, the triple combination treatment of saquinavir, zalcitabine, and zidovudine was as safe and was more effective than saquinavir/ZDV or ddC/ZDV in this 24 week study.