Los Angeles,
California
90095
Purpose:
Primary: To compare the toxicity of daily versus weekly dapsone in HIV-infected infants and
children; to study the pharmacokinetics of orally administered dapsone in HIV-infected
infants and children.
Secondary: To obtain information on the rate of Pneumocystis carinii pneumonia ( PCP )
breakthrough in children receiving two different dose regimens of dapsone.
Prophylaxis for Pneumocystis carinii pneumonia ( PCP ) is recommended for all HIV-infected
children considered to be at high risk. Approximately 15 percent of children are intolerant
to trimethoprim / sulfamethoxazole, the first choice drug for PCP prophylaxis. Since many
children are also unable to take or tolerate aerosolized pentamidine, dapsone is a second
choice for PCP prophylaxis. The most favorable dose regimen for dapsone has not been
established.
Study summary:
Prophylaxis for Pneumocystis carinii pneumonia ( PCP ) is recommended for all HIV-infected
children considered to be at high risk. Approximately 15 percent of children are intolerant
to trimethoprim / sulfamethoxazole, the first choice drug for PCP prophylaxis. Since many
children are also unable to take or tolerate aerosolized pentamidine, dapsone is a second
choice for PCP prophylaxis. The most favorable dose regimen for dapsone has not been
established.
Ninety-six HIV-infected infants and children who are intolerant to trimethoprim /
sulfamethoxazole ( TMP / SMX ) are randomized to receive oral dapsone in a lower dose once
daily or at a higher dose once weekly. Treatment continues until the last patient enrolled
has received at least 3 months of therapy. Blood samples are drawn between weeks 4 and 8, at
weeks 12 and 24, and every 3 months thereafter during dapsone administration.
Criteria:
Inclusion Criteria
Concurrent Medication:
Allowed:
- Rifampin and rifampin derivatives for up to 1 week during the study.
- Rifabutin or other drugs that could alter dapsone metabolism (if prescribed by the
child's primary care physician).
Patients must have:
- Evidence of HIV infection.
PER AMENDMENT 11/16/95:
- Children who require prophylaxis. (Was written - Risk of developing PCP.)
- Known intolerance to TMP / SMX.
- Consent of parent or guardian. Patients entering this study may be co-enrolled in
other ACTG pediatric studies.
Exclusion Criteria
Co-existing Condition:
Patients with the following symptoms and conditions are excluded:
- Glucose-6-phosphate dehydrogenase deficiency.
- Known allergy to dapsone.
Concurrent Medication:
Excluded:
- Rifampin, rifampin derivatives, or oxidant drugs for more than 1 week.
Patients with the following prior conditions are excluded:
- Serious or life-threatening reactions to TMP / SMX (e.g., anaphylaxis,
Stevens-Johnson syndrome, hypotension) that would contraindicate therapy with sulfa
drugs.
Prior Medication:
Excluded:
- Prior dapsone.
- Rifampin, rifampin derivatives, or oxidant drugs within 1 week prior to study entry.
- TMP / SMX within 7 days prior to study entry (and toxicity must be clearly
resolving).
Prior Treatment:
Excluded:
- RBC transfusion within 4 weeks prior to study entry.