Comparison of the Virologic Efficacy of Nelfinavir and/or DMP 266 (Efavirenz, EFV) in Combination With One or Two New Nucleoside Analogs in Nucleoside Experienced Subjects: A Roll-Over Study to ACTG 302/303

Inclusion Criteria

Concurrent Medication:

Required:

• Chemoprophylaxis for Pneumocystis carinii pneumonia for all patients who have a CD4 count of 200 cells/mm3 or less.

Allowed:

• Topical and oral antifungal except for oral ketoconazole.
• Treatment, maintenance, or chemoprophylaxis with approved agents for opportunistic infections as clinically indicated.
• All antibiotics as clinically indicated.
• Systemic corticosteroid use for no more than 21 days for acute problems as medically indicated. Note: Steroid use for more than 21 days is considered on a case-by-case basis.
• Recombinant erythropoietin (rEPO) and granulocyte colony-stimulating factor (G-CSF) as medically indicated.
• Regularly prescribed medications such as antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives, megestrol acetate, testosterone, or any other medications as medically indicated.

[AS PER AMENDMENT 4/25/00:

Allowed with caution:

• Pentamidine, allopurinol, hydroxyurea. Use of these medications may increase exposure to ddI.]

Concurrent Treatment:

Allowed:

• Dependency of less than 3 units of blood per 21-day period.
• Alternative therapies such as acupuncture and visualization techniques.

Patients must have:

• HIV infection documented by a licensed ELISA and confirmed by Western blot, positive HIV culture, positive HIV antigen, positive plasma HIV RNA, or second antibody test positive by a method other than ELISA. Repeat HIV-antibody testing is not required for enrollment in this trial (implicit in patients having been enrolled in ACTG 302/303).
• Signed, informed consent from parent or legal guardian for patients under 18 years of age.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Inability to tolerate ddI at 200-400 mg/day, 3TC at 300 mg/day, or d4T at 60-80 mg/day, with intolerance defined as recurrent toxicities requiring dose interruptions and reductions or permanent discontinuation of the drugs (other than Grade 3 or 4 anemia).
• Grade 2 or higher peripheral neuropathy.
• Malignancy requiring systemic therapy.
• Co-enrollment in other antiretroviral protocols; co-enrollment in other ACTG protocols is encouraged, particularly those involving prophylaxis for opportunistic infections.

Concurrent Medication:

Excluded:

• All antiretroviral therapies other than study medications.
• Investigational drugs and vaccines without specific approval from the Protocol Chair/Vice Chairs.
• Systemic cytotoxic chemotherapy.
• Interferon, interleukins, GM-CSF, and HIV-1 vaccines.
• Rifabutin and rifampin.
• Ketoconazole, astemizole, cisapride, midazolam, terfenadine, and triazolam.
• Acute therapy for an infection or other medical illness.
• Herbal medications.
• Vitamins. [10. AS PER AMENDMENT 3/5/98:
• Ergot alkaloids or drugs containing derivatives or ergot alkaloids.]

Patients with the following prior conditions are excluded:

• History of acute or chronic pancreatitis.

Prior Medication:

Excluded:

• PIs.
• NNRTIs.
• Acute therapy for an infection or other medical illness within 14 days prior to the time of study entry.
• Chronic long-term steroid use is not permitted unless it is within physiologic replacement levels; protocol chair/vice chairs must be contacted in these instances.

Risk Behavior:

Excluded:

• Current ethanol abuse by personal history or a report from a primary physician.

History of severe allergic reactions to study medication Currently pregnant or breastfeeding Recent participation in another clinical trial within the last 30 days Presence of uncontrolled medical conditions that could affect safety