Comparison of Two Dosage Regimens of Oral Dapsone for Prophylaxis of Pneumocystis Carinii Pneumonia in Pediatric HIV Infection

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 1

Conditions: Pneumonia, Pneumocystis Carinii; HIV Infections

Treatments: Drug: Dapsone

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT00000739

ACTG 179

11154 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Sex: All

Ages: 1 month to 12 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.