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.
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.
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.
San Juan City Hosp, San Juan 009367344, Puerto Rico
Univ of Alabama at Birmingham Schl of Med / Pediatrics, Birmingham, Alabama 35294, United States
San Francisco Gen Hosp, San Francisco, California 941102859, United States
Stanford Univ Med Ctr, Stanford, California 943055107, United States
Summitt Med Ctr / San Francisco Gen Hosp, Oakland, California 94609, United States
Univ of Southern California / LA County USC Med Ctr, Los Angeles, California 900331079, United States
Children's Hosp of Los Angeles, Los Angeles, California 90027, United States
Harbor UCLA Med Ctr, Torrance, California 90502, United States
San Mateo AIDS Program / Stanford Univ, Stanford, California 943055107, United States
Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States
Denver Dept of Health and Hosps, Denver, Colorado 80262, United States
Kaiser Permanente Franklin Med Ctr, Denver, Colorado 80262, United States
Rose Med Ctr, Denver, Colorado 80262, United States
Univ of Miami School of Medicine, Miami, Florida 331361013, United States
Univ of Florida Health Science Ctr / Pediatrics, Jacksonville, Florida 32209, United States
Queens Med Ctr, Honolulu, Hawaii 96816, United States
Univ of Hawaii, Honolulu, Hawaii 96816, United States
Northwestern Univ Med School, Chicago, Illinois 60611, United States
Rush Presbyterian - Saint Luke's Med Ctr, Chicago, Illinois 60612, United States
Cook County Hosp, Chicago, Illinois 60612, United States
Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States
Methodist Hosp of Indiana / Life Care Clinic, Indianapolis, Indiana 46202, United States
Tulane Univ / Charity Hosp of New Orleans, New Orleans, Louisiana 701122699, United States
Johns Hopkins Hosp, Baltimore, Maryland 21287, United States
State of MD Div of Corrections / Johns Hopkins Univ Hosp, Baltimore, Maryland 212052196, United States
Harvard (Massachusetts Gen Hosp), Boston, Massachusetts 02114, United States
Beth Israel Deaconess Med Ctr, Boston, Massachusetts 02215, United States
Beth Israel Deaconess - West Campus, Boston, Massachusetts 02215, United States
Boston Med Ctr, Boston, Massachusetts 02118, United States
Univ of Minnesota, Minneapolis, Minnesota 55455, United States
St Paul Ramsey Med Ctr, St. Paul, Minnesota 55101, United States
Hennepin County Med Clinic, Minneapolis, Minnesota 55415, United States
St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis, Missouri 63112, United States
Univ of Nebraska Med Ctr, Omaha, Nebraska 681985130, United States
Montefiore Family Health Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States
SUNY / State Univ of New York, Syracuse, New York 13210, United States
Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States
Mount Sinai Med Ctr, New York, New York 10029, United States
Jack Weiler Hosp / Bronx Municipal Hosp, Bronx, New York 10465, United States
Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx, New York 10461, United States
Montefiore Med Ctr / Bronx Municipal Hosp, Bronx, New York 10467, United States
Bronx Veterans Administration / Mount Sinai Hosp, Bronx, New York 10468, United States
SUNY / Erie County Med Ctr at Buffalo, Buffalo, New York 14215, United States
Beth Israel Med Ctr, New York, New York 10003, United States
City Hosp Ctr at Elmhurst / Mount Sinai Hosp, Elmhurst, New York 11373, United States
North Central Bronx Hosp / Bronx Municipal Hosp, Bronx, New York 10467, United States
Comprehensive Health Care Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States
Adirondack Med Ctr at Saranac Lake, Albany, New York 122083479, United States
Mid - Hudson Care Ctr, Albany, New York 122083479, United States
Albany Med College / Division of HIV Medicine A158, Albany, New York 122083479, United States
Montefiore Med Ctr Adolescent AIDS Program, Bronx, New York 10467, United States
Montefiore Adolescent AIDS Prog / Bronx Municipal Hosp, Bronx, New York 10461, United States
Carolinas Med Ctr, Charlotte, North Carolina 28203, United States
Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States
Moses H Cone Memorial Hosp, Greensboro, North Carolina 27401, United States
Univ of Cincinnati, Cincinnati, Ohio 452670405, United States
Ohio State Univ Hosp Clinic, Columbus, Ohio 432101228, United States
MetroHealth Med Ctr, Cleveland, Ohio 441091998, United States
Univ of Pennsylvania at Philadelphia, Philadelphia, Pennsylvania 19104, United States
Thomas Jefferson Univ Hosp, Philadelphia, Pennsylvania 191075098, United States
Julio Arroyo, West Columbia, South Carolina 29169, United States
Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr, Knoxville, Tennessee 37920, United States
Meharry Med College, Nashville, Tennessee 37203, United States
Univ of Washington, Seattle, Washington 981224304, United States
Para MF, Dohn M, Frame P, Becker S, Finkelstein D, Walawander A. ACTG 268 trial - gradual initiation of trimethoprim/sulfamethoxazole (T/S) as primary prophylaxis for Pneumocystis carinii pneumonia (PCP). Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:65 (abstract no 2)
Para MF, Finkelstein D, Becker S, Dohn M, Walawander A, Black JR. Reduced toxicity with gradual initiation of trimethoprim-sulfamethoxazole as primary prophylaxis for Pneumocystis carinii pneumonia: AIDS Clinical Trials Group 268. J Acquir Immune Defic Syndr. 2000 Aug 1;24(4):337-43.
