AIDS Clinical Trials Group study 359 was a controlled study of saquinavir with either ritonavir or nelfinavir, together with delavirdine, adefovir, or both, in indinavir-experienced persons. Saquinavir was common in all study arms, and the study investigated relationships among characteristics of patients, saquinavir area under the curve (AUC) and trough concentrations (C(min)), and virologic response. Concentrations of saquinavir were higher when it was combined with ritonavir than when it was combined with nelfinavir and were lower with adefovir-containing regimens. Females had higher AUC and C(min) values than did males. Higher saquinavir AUC and C(min) values were associated with a greater likelihood of human immunodeficiency virus (HIV) RNA levels </=500 copies/mL (P=.008) and were better predictors of response than was the saquinavir inhibitory quotient. Males had a lower probability of having HIV RNA levels </=500 copies/mL at week 16 than did females (28% vs. 42%; adjusted odds ratio, 0.43). In this study, a greater proportion of females had HIV RNA levels </=500 copies/mL than did males, which can be attributed to higher concentrations of saquinavir in females than in males.