A Comparison of Atovaquone and Pentamidine in the Prevention of Pneumocystis Carinii Pneumonia in HIV-Infected Patients Who Cannot Take TMP/SMX

Patients are randomized to receive oral atovaquone at 1 of 2 doses once daily or aerosolized pentamidine once every 4 weeks. Treatment continues until 18 months after the last patient is enrolled. Patients are stratified into primary or secondary prophylaxis strata based on prior occurrence of a PCP episode.

Inclusion criteria

Concurrent Medication:

Allowed:

• Antimicrobial agents not specifically prohibited.

Concurrent Treatment:

Allowed:

• Transfusion.

Patients must have:

• HIV positivity.
• Prior PCP (histologically confirmed) OR documented CD4 count < 200 cells/mm3 OR constitutional symptoms such as thrush or unexplained fever (> 100 F) for 2 or more weeks.
• No current or suspected active PCP, and no signs of active PCP on chest x-ray.
• Prior intolerance to TMP/SMX or other trimethoprim or sulfa-containing regimens.
• Life-expectancy of at least 6 months.

NOTE:

• Pregnant women are eligible at the discretion of the investigator.

Exclusion criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Significant psychosis or emotional disorder that would preclude study compliance.
• Severe chronic diarrhea (e.g., > five stools/day) that may negatively affect absorption of oral medication.
• Unable to take oral medication or unable or unwilling to take medication with food.

Concurrent Medication:

Excluded:

• Rifampin.
• Other investigational agents except for drugs available through Treatment INDs or expanded access programs.
• Medications likely to have anti-pneumocystis effect (e.g., dapsone, trimethoprim, pyrimethamine, trimetrexate, other DHFR inhibitors, sulfadiazine, sulfamethoxazole, other sulfonamides, primaquine, clindamycin, and sulfonylureas.
• Corticosteroids in greater than physiologic replacement doses for more than 21 consecutive days.
• Systemic therapy for CNS toxoplasmosis, Kaposi's sarcoma, lymphoma, other active malignancies, or other disease that may decrease life expectancy or confound assessment.

Patients with the following prior conditions are excluded:

• History of severe or intractable intolerance to atovaquone or aerosolized pentamidine.
• Prior hypoglycemia, pancreatitis, arrhythmias, or severe hypotension associated with any form of pentamidine.
• Prior enrollment in this protocol. Active substance abuse that would preclude study compliance.