This is a phase I/II open label combination therapy study in two parts separated by at least eight weeks. In Part 1, HIV-infected infants and children will receive therapy with saquinavir plus two nucleoside antiretroviral agents chosen by the investigator and patient (or guardian). In Part 2, HIV-infected infants and children will receive therapy with saquinavir, nelfinavir and nucleoside antiretroviral agent(s) as chosen by the investigator and patient (or guardian). At least four patients (two each in Parts 1 and 2) will be enrolled in each of three age strata: six months to two years; greater than two years to six years; and greater than six years to 13 years. Each patient will receive therapy for at least 24 weeks. Clinical and laboratory pharmacokinetic, safety, virologic, and immunologic evaluations will be performed every four weeks for the first 16 weeks and then every eight weeks until week 72. Pharmacokinetic studies will be done at day 0, day 1, every four weeks until week 24, and at week 72 in patients who are willing and able to take both the adult and pediatric formulations, and patients who take only one formulation will have pharmacokinetic studies done at day 0, every four weeks until week 24, and at week 72. Saquinavir dosing may be adjusted based on the results of initial pharmacokinetic studies. Any patient in Part 1 who does not achieve acceptable saquinavir levels after dose adjustment will be given the opportunity to further modify dose and/or dose interval, or add nelfinavir to the original regimen at week eight. Preliminary study results indicate that both treatment regimens are associated with excellent short-term safety and tolerability. Most patients in both study parts have had suppression of virus load below levels of detectability. This study formed the basis for a multicenter AIDS Clinical Trials Group protocol (ACTG 397).
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