Comparison of Stavudine Used Alone or in Combination With Didanosine in HIV-Infected Children

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 2

Conditions: HIV Infections

Treatments: Drug: Didanosine; Drug: Stavudine

Study type: Interventional

Funder types: NIH

Identifiers

NCT00000851

ACTG 327

11300 (Registry Identifier)

Details and patient eligibility

About

To evaluate the safety and determine the pharmacokinetic disposition of stavudine (d4T) alone and in combination with didanosine (ddI), and whether concurrent administration alters the disposition of either drug. To compare d4T versus d4T plus ddI with respect to short and long term changes from baseline in plasma HIV RNA concentrations. To determine the relationship, if any, between drug exposure and viral burden.

In a pilot study of d4T and ddI given to eight children with advanced HIV for 24 weeks, the three children with baseline counts greater than 50 cells/micro liter experienced a 20% increase in their CD4+ lymphocyte counts. Based on these results, controlled trials of the same regimen for children with less advanced HIV disease should be undertaken.

Full description

In a pilot study of d4T and ddI given to eight children with advanced HIV for 24 weeks, the three children with baseline counts greater than 50 cells/micro liter experienced a 20% increase in their CD4+ lymphocyte counts. Based on these results, controlled trials of the same regimen for children with less advanced HIV disease should be undertaken.

Eligible subjects receiving d4T will be assigned in an open manner to Arm 1, and subjects who have been receiving zidovudine (AZT) will be assigned in a randomized, double blind manner to Arms 2 and 3. Each subject will receive study drug for 48 weeks as follows: Arm 1 - d4T plus ddI, Arm 2 - d4T alone, Arm 3 - d4T plus ddI.

Sex: All

Ages: 6 months to 10 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Patients must:

• Be on-study, on-treatment in ACTG 240, or receiving AZT monotherapy by prescription for at least 6 months immediately preceding enrollment.
• Have laboratory evidence of HIV-1 infection < 18 months - 2 positive viral tests >= 18 months - 2 positive viral tests or 2 or more positive tests for HIV antibody
• Have parent or legal guardian willing to sign a consent.

Prior Medication: Required:

• On-study, on-treatment in ACTG 240 (D4T or AZT) or receiving AZT monotherapy by prescription for at least six months immediately preceding this trial.

Exclusion Criteria

Co-existing Condition:

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

• Intractable diarrhea or vomiting.
• Current clinical or laboratory Grade 3 or worse toxicities.

Concurrent Medication:

Excluded:

• Concurrent use of antiretroviral agents other than those provided by the study, immunomodulators (other than IVIG or corticosteroids), or other investigational drugs except for those in ACTG 254 and ACTG 219.
• Chemotherapy for active malignancy.

Patients with any of the following prior conditions are excluded:

• Reached an ACTG 240 defined endpoint, or are permanently off ACTG 240 study treatment.
• Prescription AZT recipients may not have received > 6 weeks of d4T or ddI previously.
• Subjects who have had chemotherapy for active malignancy.

Prior Medication:

Excluded:

• Prescription AZT recipients may not have received > 6 weeks of d4T or ddI previously.