A Randomized, Comparative Study of Daily Dapsone and Daily Atovaquone for Prophylaxis Against PCP in HIV-Infected Patients Who Are Intolerant of Trimethoprim and/or Sulfonamides

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 3

Conditions: Pneumonia, Pneumocystis Carinii; HIV Infections

Treatments: Drug: Dapsone; Drug: Atovaquone

Study type: Interventional

Funder types: NIH

Identifiers

NCT00000802

CPCRA 034

11253 (Registry Identifier)

ACTG 277

Details and patient eligibility

About

To compare the efficacy and safety of dapsone versus atovaquone in preventing or delaying the onset of histologically proven or probable Pneumocystis carinii pneumonia in HIV-infected patients with CD4 counts <= 200 cells/mm3 or <= 15 percent of the total lymphocyte count who are intolerant to trimethoprim and/or sulfonamides.

Trimethoprim/sulfamethoxazole (TMP/SMX), which is effective for secondary PCP prophylaxis, is associated with allergic manifestations and side effects that limit its use. Patients who are intolerant of TMP/SMX require an effective alternative. Dapsone and atovaquone have both shown promise as PCP prophylactic agents.

Full description

Trimethoprim/sulfamethoxazole (TMP/SMX), which is effective for secondary PCP prophylaxis, is associated with allergic manifestations and side effects that limit its use. Patients who are intolerant of TMP/SMX require an effective alternative. Dapsone and atovaquone have both shown promise as PCP prophylactic agents.

Patients are randomized to receive either dapsone or atovaquone daily, with follow-up at the clinic every 4 months.

Sex: All

Ages: 13+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Concurrent Medication: Strongly recommended:

• Pyrimethamine (50 mg) and folinic acid (15 mg) weekly in patients receiving dapsone who have CD4 count < 100 cells/mm3 and are toxoplasmosis seropositive.

Patients must have:

• Working diagnosis of HIV infection.
• CD4 count <= 200 cells/mm3 or <= 15 percent of total lymphocyte count at any time in the past OR a history of PCP.
• History of intolerance of trimethoprim and/or sulfonamides that required permanent discontinuation.

NOTE:

• Pregnant patients are eligible at the clinician's discretion.

Prior Medication:

Allowed:

• Prior PCP prophylaxis.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Active pneumocystosis.

Concurrent Medication:

Excluded:

• PCP prophylaxis (other than study drug) or any medication with potential anti-PCP activity.

Patients with the following prior conditions are excluded:

• Known treatment-limiting reaction to dapsone or atovaquone.