In this study of pharmacokinetic interactions, (1) the effect of ritonavir on the pharmacokinetics of amprenavir; (2) the effect of efavirenz on the pharmacokinetics of amprenavir and ritonavir, and (3) the effect of efavirenz on the pharmacokinetics of amprenavir and nelfinavir were examined. Twenty-two patients who have a viral burden of at least 500 copies/mL on combination therapy with a protease inhibitor for at least 20 weeks were to be enrolled to receive open-label treatment, 6 with abacavir 300 mg po BID, amprenavir 1200 mg po BID, ritonavir 200 mg po BID and efavirenz 600 mg po QD, 6 with abacavir 300 mg po BID, amprenavir 1200 mg po BID, ritonavir 500 mg po BID and efavirenz 600 mg po QD, and 10 with abacavir 300 mg po BID, amprenavir 1200 mg po BID, nelfinavir 1250 mg po BID and efavirenz 600 mg po QD. The groups enrolled sequentially: low-dose ritonavir combination group, then the full dose ritonavir combination group, and then the nelfinavir combination group. Subjects were seen at pre-entry, baseline (Day 1), and thereafter at study weeks 1 (serial sampling), 2 (serial sampling), 4, 8, 12, 16, 24 then every 8 weeks through one year. Patients discontinued current therapy and without a washout period began dosing. For the groups who will receive ritonavir, the schedule was: dose with abacavir and amprenavir and, after one-week, serial plasma sampling was performed for baseline amprenavir levels. Next ritonavir at the assigned dose was added (for the full-dose, there is a rapid dose escalation) and plasma sampling was repeated one week later; finally, efavirenz 600 mg once daily will be added and plasma sampling was again be repeated between 2 weeks after beginning the combination. For the nelfinavir group, the schedule was: dose with nelfinavir, amprenavir, and abacavir for one week and obtain serial plasma sampling, then add efavirenz for another week and obtain serial plasma sampling. Patients with a confirmed increase in viral burden of one log or greater from baseline will end study participation. The safety and antiviral activity of each combination were also assessed and continue to be assessed; toxicity management is outlined in the protocol. This study remains open in order to continue to provide these drugs to subjects who completed the original one-year study period and who wish to continue medications that appear, by viral load, to be of benefit to them.