We evaluated the degree of correlation between the variation of different HIV-1 viral load measures in response to antiretroviral therapy. A quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for plasma HIV-RNA, and HIV plasma infectivity titration, were performed on prospective samples obtained from 86 antiretroviral-naive patients with symptomatic infection and CD4+ < 300/mm3, enrolled in a randomized double-blind trial of the HIV protease inhibitor saquinavir (SQV) in combination with zidovudine (ZDV). Subjects were stratified according to plasma virus infectivity and examined for correlations between distinct response categories with respect to CD4 count and HIV RNA copy number changes. Infectious virus could be titrated in 72% of patients at baseline. A significant reduction (< 1 log10) in HIV plasma infectivity titer was observed during the study in 69% of these patients. The reduction in plasma infectivity was a good predictor of sustained CD4+ cell increases and of sustained decrease in HIV RNA plasma copies. A decrease of at least 0.5 log10 in HIV RNA copy number was observed in 82% of the treated patients. A good correlation was found between HIV plasma infectivity titer and plasma HIV RNA copy number variations (p < 0.001). However, 10 of 17 patients with unchanged plasma infectivity titer showed a significant reduction in HIV RNA copies. While a good correlation was found between plasma infectivity and RNA plasma copies variations, only a minor correlation was found between CD4+ cell count variation and plasma infectivity titer variation. However, reduction in plasma infectivity was a very good predictor of high CD4 changes.