The Safety and Effectiveness of Lamivudine Plus Stavudine or Zidovudine in HIV-Infected Patients Who Have Taken Zidovudine

Patients will be randomized to either Stavudine (d4T) + Lamivudine (3TC) + Zidovudine placebo or Zidovudine (ZDV) + Lamivudine + Stavudine placebo. Patients whose plasma HIV RNA levels remain >= 500 copies/ml after 8 weeks of blinded double combination therapy will have indinavir added to their treatment regimen at the week 12 visit.

Inclusion criteria

Patients must have:

• At least six months of prior cumulative ZDV therapy.
• Qualifying plasma HIV RNA count of >= 4 log10 copies/ml obtained within 2 weeks of randomization.

Exclusion criteria

Co-existing Condition:

Patients with any of the following symptoms or conditions are excluded:

• Presence of newly diagnosed AIDS defining opportunistic infection requiring acute therapy at time of enrollment.
• Intractable diarrhea (>= 6 loose stools/day for >= 7 consecutive days).
• Signs and symptoms of bilateral peripheral neuropathy >= grade 2 at the time of screening.
• Inability to tolerate oral medication.
• Any other clinical conditions that in the opinion of the investigator, would make the patient unsuitable for study or unable to comply with the dosing requirements.

Concurrent Medication:

Excluded:

• Therapy with agents with systemic myelosuppressive, neurotoxic pancreatotoxic, hepatotoxic or cytotoxic potential.
• Therapy with rifampin, rifabutin, terfenadine, astemizole, cisapride, triazolam, midazolam and ketoconazole at any time while on indinavir therapy.

Patients with any of the following prior conditions or symptoms are excluded:

• History of acute or chronic pancreatitis.
• Prior history of bilateral peripheral neuropathy.
• Intractable diarrhea (>= 6 loose stools/day for >= 7 consecutive days) within 30 days prior to study entry.

Prior Medication:

Excluded:

• Any prior antiretroviral therapy except for ddI, ddC, 3TC or ZDV (for ZDV, as specified in inclusion criteria).
• Previous therapy with agents with significant systemic myelosuppressive, neurotoxic pancreatotoxic, hepatotoxic or cytotoxic potential within 3 months of study start.
• Therapy with rifampin, rifabutin, terfenadine, astemizole, cisapride, triazolam, midazolam and ketoconazole within 2 weeks prior to starting indinavir.
• Any other prior therapy that, in the opinion of the investigator, would make the patient unsuitable for study or unable to comply with the dosing regimen.

Risk Behavior:

Excluded:

• Active alcohol abuse, sufficient in the investigator's opinion, to prevent compliance with study therapy or to increase the risk of developing pancreatitis.

Required:

At least 6 months of prior cumulative ZDV therapy.