Gradual Initiation of Sulfamethoxazole/Trimethoprim as Primary Pneumocystis Carinii Pneumonia Prophylaxis

To determine whether gradual initiation of sulfamethoxazole/trimethoprim (SMX/TMP) reduces the incidence of treatment-limiting adverse reactions compared to the routine initiation of the drugs for Pneumocystis carinii pneumonia (PCP) prophylaxis in HIV-infected patients.

Although a number of clinical trials have demonstrated the superiority of SMX/TMP for PCP prophylaxis, the incidence of adverse reactions to this medication is high. In a pilot study in which patients were initiated with SMX/TMP prophylaxis by gradually increasing the dose over 2 weeks, no significant adverse reactions have occurred.

Although a number of clinical trials have demonstrated the superiority of SMX/TMP for PCP prophylaxis, the incidence of adverse reactions to this medication is high. In a pilot study in which patients were initiated with SMX/TMP prophylaxis by gradually increasing the dose over 2 weeks, no significant adverse reactions have occurred.

Patients are randomized to receive either gradually increasing doses of SMX/TMP suspension or routine daily initiation of SMX/TMP double strength (DS) tablets for 2 weeks. All patients will then be switched over to receive open-label SMX/TMP DS tablets daily for 10 weeks.

Eligibility Criteria:
Inclusion Criteria

Concurrent Medication:

Allowed if clinically indicated:

* Recombinant erythropoietin (rEPO) and G-CSF.

Allowed for symptomatic treatment of mild study drug toxicity:

* Antipyretics and analgesics (ibuprofen).
* Antihistamines (diphenhydramine HCl).
* Terfenadine or astemizole (but not allowed with concomitant antifungal or macrolide use).
* Systemic steroids.

Patients must have:

* HIV infection.
* CD4 count \<= 250 cells/mm3 OR history or presence of thrush.
* No history of confirmed or probable pneumocystosis.

NOTE:

* Pregnant women are not excluded, but safety issues should be discussed with patient prior to enrollment.
* This study is appropriate for prisoner participation.
* Coenrollment in ongoing ACTG antiretroviral studies is permitted provided no new study drugs are added to the patient's drug regimen for 4 weeks before or after initiation of SMX/TMP.

Prior Medication:

Allowed:

* Prior aerosolized pentamidine and dapsone for primary PCP prophylaxis.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

* Known adverse reactions to sulfa, trimethoprim, or SMX/TMP.
* Inability to comply with dosing schedule or complete dosing record.

Concurrent Medication:

Excluded:

* Procysteine.
* Glutathione.
* N-acetylcysteine (NAC).
* Antihistamines (unless used for symptomatic treatment of study drug toxicity).
* Systemic corticosteroids (unless used for replacement purposes).
* Leucovorin calcium (unless used for symptomatic treatment of study drug toxicity).
* TMP or sulfa drugs outside of the study.

Prior Medication:

Excluded at any time:

* Prior SMX/TMP as primary PCP prophylaxis.

Excluded within 4 weeks prior to study entry:

* Initiation of antiretroviral agents.
* Initiation of anti-infective agents (including SMX/TMP for another indication).

Excluded within 2 weeks prior to study entry:

* Antihistamines.
* Procysteine.
* Glutathione.
* N-acetylcysteine (NAC).
* Systemic corticosteroids (unless used for replacement purposes).
* Leucovorin calcium.
* TMP and sulfa drugs separately.