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.

Condition	Treatment or Intervention	Phase
Pneumonia, Pneumocystis carinii HIV Infections	Drug: Sulfamethoxazole-Trimethoprim	Phase IV

Further Study Details: 

Expected Total Enrollment:  370

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.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

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.

Alabama
      Univ of Alabama at Birmingham Schl of Med / Pediatrics, Birmingham,  Alabama,  35294,  United States
California
      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
Colorado
      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
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States
      Univ of Florida Health Science Ctr / Pediatrics, Jacksonville,  Florida,  32209,  United States
Hawaii
      Queens Med Ctr, Honolulu,  Hawaii,  96816,  United States
      Univ of Hawaii, Honolulu,  Hawaii,  96816,  United States
Illinois
      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
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
      Methodist Hosp of Indiana / Life Care Clinic, Indianapolis,  Indiana,  46202,  United States
Louisiana
      Tulane Univ / Charity Hosp of New Orleans, New Orleans,  Louisiana,  701122699,  United States
Maryland
      Johns Hopkins Hosp, Baltimore,  Maryland,  21287,  United States
      State of MD Div of Corrections / Johns Hopkins Univ Hosp, Baltimore,  Maryland,  212052196,  United States
Massachusetts
      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
Minnesota
      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
Missouri
      St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis,  Missouri,  63112,  United States
Nebraska
      Univ of Nebraska Med Ctr, Omaha,  Nebraska,  681985130,  United States
New York
      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
North Carolina
      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
Ohio
      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
Pennsylvania
      Univ of Pennsylvania at Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
      Thomas Jefferson Univ Hosp, Philadelphia,  Pennsylvania,  191075098,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
Tennessee
      Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr, Knoxville,  Tennessee,  37920,  United States
      Meharry Med College, Nashville,  Tennessee,  37203,  United States
Washington
      Univ of Washington, Seattle,  Washington,  981224304,  United States
Puerto Rico
      San Juan City Hosp, San Juan,  009367344,  Puerto Rico

Study chairs or principal investigators

Para MF,  Study Chair
Dohn MN,  Study Chair
Frame P,  Study Chair

Study ID Numbers:  ACTG 268
Record last reviewed:  October 1996
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000816
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08