A Comparative Study of Combination Antiretroviral Therapy in Children and Adolescents With Advanced HIV Disease

The duration of clinical benefit from zidovudine (AZT) may be limited because of development of viral resistance to the drug. Use of combination antiretroviral therapy can potentially reduce viral load and prevent emergence of multidrug resistance.

In Stage 1 of the study, a minimum of 22 patients are randomized to each of three treatment arms: didanosine (ddI) plus AZT plus nevirapine (NVP); ddI plus AZT; and ddI plus NVP. After 12 weeks of treatment, the study proceeds to Stage 2 provided at least 40 percent of patients in Stage 1 show a reduction of at least 40 percent from baseline ICD p24 antigen of greater than or equal to 70 pg/ml AND fewer than two patients experience grade 4 rash. Patients in Stage 1 continue treatment for an additional 36 weeks. In Stage 2, additional patients are randomized to each original treatment regimen until a maximum of 130 patients per arm have been entered. Stage 2 patients receive treatment for at least 48 weeks.

AS PER AMENDMENT 02/12/97: As of 2/28/97, patients receiving study drugs will be offered blinded study drugs for an additional 16 weeks (until 6/30/97). Patients will be unblinded on or about 5/23/97.

Inclusion criteria

Concurrent Medication:

Allowed:

• Erythropoietin.

Concurrent Treatment:

Allowed:

• Transfusion.

Patients must have:

• Progressive HIV disease.
• At least 24 weeks prior cumulative nucleoside analog antiretroviral monotherapy or combination therapy.

Exclusion criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Active malignancy requiring chemotherapy.
• Currently receiving therapy in an ACTG primary therapy or salvage protocol who have NOT met an endpoint on that study.
• Known intolerance (other than hematologic) or toxicity to ddI, AZT, or NVP at the doses used in this study.

Concurrent Medication:

Excluded (unless exemption made by study chair):

• Oral anticoagulants (warfarin, dicumarol).
• Oral contraceptives.
• Digitalis glycosides.
• Phenytoin.
• Theophylline.

Patients with the following prior conditions are excluded:

• History of clinical pancreatitis.
• History of grade 2 or worse peripheral neuropathy.

Prior Treatment:

Excluded:

• Acute treatment for a serious bacterial, viral, or opportunistic infection within 14 days prior to study entry.