PRIMARY: To compare the relative safety and tolerance of oral zidovudine (AZT) versus oral stavudine (d4T) in symptomatic HIV-infected children.

SECONDARY: To compare the clinical, virologic, and immunologic responses between the two treatment groups, and to obtain pharmacokinetic data for both drugs.

At present, AZT is considered the drug of choice for initial treatment of most children with HIV infection, although disease progression or drug intolerance is associated with its long-term use. In preliminary studies in children, d4T, another HIV inhibitor, has been well tolerated, although an optimum dose has not been determined.

At present, AZT is considered the drug of choice for initial treatment of most children with HIV infection, although disease progression or drug intolerance is associated with its long-term use. In preliminary studies in children, d4T, another HIV inhibitor, has been well tolerated, although an optimum dose has not been determined.

Patients are randomized to receive either oral AZT or oral d4T. Treatment continues until the last patient enrolled has received 52 weeks of therapy, or until the study is terminated.

• Drug: Stavudine
• Drug: Zidovudine

• Kline MW, Fletcher CV, Federici ME, Harris AT, Evans KD, Rutkiewicz VL, Shearer WT, Dunkle LM. Combination therapy with stavudine and didanosine in children with advanced human immunodeficiency virus infection: pharmacokinetic properties, safety, and immunologic and virologic effects. Pediatrics. 1996 Jun;97(6 Pt 1):886-90.
• Kline MW, Van Dyke RB, Lindsey JC, Gwynne M, Culnane M, McKinney RE Jr, Nichols S, Mitchell WG, Yogev R, Hutcheon N. A randomized comparative trial of stavudine (d4T) versus zidovudine (ZDV, AZT) in children with human immunodeficiency virus infection. AIDS Clinical Trials Group 240 Team. Pediatrics. 1998 Feb;101(2):214-20.
• Dankner WM, Lindsey JC, Levin MJ. Correlates of opportunistic infections in children infected with the human immunodeficiency virus managed before highly active antiretroviral therapy. Pediatr Infect Dis J. 2001 Jan;20(1):40-8.

Inclusion Criteria

Concurrent Medication:

Recommended:

• PCP prophylaxis.

Allowed:

• Immunoglobulin.
• Erythropoietin, G-CSF, and GM-CSF.
• Corticosteroids.
• Ethionamide or isoniazid for TB if no alternative is available.
• Pyridoxine (up to 50 mg/day) as vitamin supplement.

Patients must have:

• Symptomatic HIV infection.
• No more than 6 weeks of prior antiretroviral or immunomodulator therapy (other than steroids and IVIG).
• Consent of parent or guardian.

NOTE:

• Coenrollment on another ACTG protocol not involving antiretroviral therapy is permitted.

Prior Medication:

Allowed:

• Maternal immunomodulator or antiretroviral therapy (including during pregnancy).
• Antiretroviral therapy prior to 2 months.
• Up to 6 weeks of prior antiretroviral therapy or specific immunomodulator therapy (other than corticosteroids and IVIG).

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Current grade 3 or worse neuropathy / lower motor neuropathy.
• Other grade 3 or worse clinical or laboratory toxicities.
• Known intolerance to either AZT or d4T.

Concurrent Medication:

Excluded:

• Chemotherapy for active malignancy.

Patients with the following prior conditions are excluded:

• History of grade 3 or worse neuropathy/lower motor neuropathy.

Prior Medication:

Excluded:

• More than 6 weeks of prior antiretroviral or immunomodulator therapy.
• Antiretroviral or immunomodulator therapy within 7 days prior to study entry. Ongoing drug or alcohol abuse.

• Glaxo Wellcome
• Bristol-Myers Squibb