An Open-Label, Staggered Rising Dose Cohort Study Assessing the Pharmacokinetics, Safety, and Tolerance of BI-RG-587 in Combination With Zidovudine in Patients With HIV Infection (CD4+ Cell Count < 400/mm3)

To assess the safety and tolerance of multiple oral doses of nevirapine in combination with zidovudine (AZT); to get information on the pharmacokinetics (blood levels) and dose proportionality of nevirapine/AZT with multiple dosing; to characterize the pattern of virological activity in vivo (in humans) of nevirapine in combination with AZT; to determine whether development of resistance to either drug is slowed by the use of the combination. Drugs now used in treatment for patients with AIDS show some toxicity which limits their usefulness. In addition, with long-term treatment with AZT, there is evidence of virus resistance to the drug. Compounds that are more effective and less toxic than those in present use would be beneficial, especially if they are active against AZT-resistant viruses. Nevirapine has shown in vitro (test tube studies) activity in inhibiting HIV replication (reproduction). In vitro studies have shown that nevirapine and AZT work together to inhibit HIV replication. Drugs now used in treatment for patients with AIDS show some toxicity which limits their usefulness. In addition, with long-term treatment with AZT, there is evidence of virus resistance to the drug. Compounds that are more effective and less toxic than those in present use would be beneficial, especially if they are active against AZT-resistant viruses. Nevirapine has shown in vitro (test tube studies) activity in inhibiting HIV replication (reproduction). In vitro studies have shown that nevirapine and AZT work together to inhibit HIV replication. Groups of 10 patients are studied at each of three dose levels. Five patients at each dose level have less than 3 months of prior AZT treatment; five patients at each dose level have at least 12 months of previous AZT treatment and tolerated an AZT regimen of 600 mg/day (200 mg every 8 hours). At least 24 patient-weeks of treatment with the combination treatment must be completed without requiring dose interruption before the next dosage level can be started. All 30 patients must be enrolled at a lower dosage level before a higher dosage level is started. Patients begin treatment with AZT. 14 days later, patients begin treatment with nevirapine in addition to the AZT. After 24 weeks, patients have the option to continue long-term treatment with either nevirapine or standard treatment.