The goal of AIDS Clinical Trials Group (ACTG) Protocol 229 was to evaluate the shorter term (24 week) and longer term (48 week) safety and activity of the HIV-1 proteinase inhibitor saquinavir in combination with zalcitabine (ddC) and zidovudine (ZDV) versus saquinavir in combination with ZDV versus ddC in combination with ZDV. This study confirms and extends the conclusions from the first 24 weeks of this study and showed that in subjects with extensive prior antiretroviral experience, the triple combination of saquinavir, ddC and ZDV was well-tolerated, safe and remained superior to the other double drug regimens as measured by CD4+ cell counts, quantitative HIV-1 microculture and plasma HIV-1 RNA levels.