To evaluate and compare 3 anti-pneumocystis regimens plus zidovudine (AZT) in persons with HIV infection and T4 cell count less than 200 cells/mm3. All persons completing at least 8 weeks of therapy on 081 will be offered the opportunity to participate in the nested study (ACTG 981) of systemic antifungal therapy (fluconazole) versus local therapy (Clotrimazole) for the prevention of serious fungal disease. Persons with HIV disease who are receiving AZT are at risk for PCP, toxoplasmosis, bacterial pneumonia, and other serious infections. It is therefore important to find drugs that can be given along with AZT to control these infections. Aerosolized pentamidine (PEN) has been shown to be useful in preventing PCP and is expected to lower the 2-year risk of PCP. Both sulfamethoxazole/trimethoprim (SMX/TMP) and dapsone probably also provide effective preventive treatment against PCP, and both may be useful in preventing toxoplasmosis and extrapulmonary pneumocystosis.

Condition	Treatment or Intervention	Phase
Pneumonia, Pneumocystis carinii HIV Infections	Drug: Pentamidine isethionate  Drug: Sulfamethoxazole-Trimethoprim  Drug: Dapsone  Drug: Zidovudine	Phase III

Further Study Details: 

Expected Total Enrollment:  600

Persons with HIV disease who are receiving AZT are at risk for PCP, toxoplasmosis, bacterial pneumonia, and other serious infections. It is therefore important to find drugs that can be given along with AZT to control these infections. Aerosolized pentamidine (PEN) has been shown to be useful in preventing PCP and is expected to lower the 2-year risk of PCP. Both sulfamethoxazole/trimethoprim (SMX/TMP) and dapsone probably also provide effective preventive treatment against PCP, and both may be useful in preventing toxoplasmosis and extrapulmonary pneumocystosis.

All patients receive AZT. In addition, they are placed in one of three groups to receive either SMX/TMP, dapsone, or PEN. Stratification criteria are: Received first AZT equal to or less than 6 weeks prior to study entry. Received first AZT more than 6 weeks prior to study entry. Potential to participate in ACTG 981. ACTG center in which the patient is enrolled.

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

Criteria

Inclusion Criteria

Concurrent Medication: Allowed:

• Antifolate medication required to treat an intercurrent infection.
• Treatment of intercurrent infections or malignancies.
• Fluconazole.
• Itraconazole.
• Standard or investigational therapy for pneumocystosis (PCP) or toxoplasmosis.
• Only the forms of primary prophylaxis for PCP or toxoplasmosis assigned to the participant under the protocol. Patients who develop intolerance to all forms of prophylaxis assigned in this protocol or who develop PCP or toxoplasmosis may receive alternate or investigation forms of prophylaxis with or without zidovudine but must continue to be followed under this protocol.
• Discouraged but allowed: AL-721.
• Chronic acyclovir.
• Ketoconazole.
• Amphotericin B.
• Corticosteroids at greater than physiologic replacement doses are strongly discouraged.
• They should be used as briefly as possible and only for definite specific indications.

Patient must conform to the following:

• Receiving or candidates for zidovudine therapy at least 500 mg/day under current labeled indications with no history of pneumocystosis (PCP) or toxoplasmosis.
• Evidence of HIV infection documented by HIV antibody tests.
• T4 cell count less than 200 cells/mm3 at any time prior to study entry.
• Willing to sign informed consent.
• Willing to be followed by a participating ACTG center for duration of the study.
• Allowed: Concurrent enrollment in long-term follow-up studies in previously blinded trials of AZT (ACTG 016 and 019).

Exclusion Criteria

Co-existing Condition: Patients with the following conditions are excluded:

• History of documented or presumed pneumocystosis (PCP) or toxoplasmosis.
• Active bacterial or mycobacterial infection.
• History of type I hypersensitivity, exfoliative rash, or rash with mucosal involvement, severe bronchospasm, or other life-threatening reaction to any of the study drugs or to other sulfas, sulfones, or pentamidine.
• History of intolerance causing dose interruption while receiving zidovudine at equal to or less than 600 mg/day or causing dose reduction to less than 500 mg/day within 4 weeks prior to entry.
• Advanced Kaposi's sarcoma or other malignancy not specifically allowed that has been rapidly progressive during the month prior to enrollment or which may be expected to require chemotherapy within 90 days of study entry.

Concurrent Medication: Excluded:

• Active primary treatment for an infection or malignancy.
• Other form of antifolate medication not specifically allowed.
• Other antiretroviral or biologic response modifier.
• Ganciclovir, if it causes intolerance to AZT equal to or more than 500 mg/day.
• Foscarnet.

Patients with the following are excluded:

• Symptoms and conditions defined in Exclusion Coexisting Conditions.
• Glucose 6-phosphate dehydrogenase deficiency (GPD).
• History of pneumocystosis (PCP) or toxoplasmosis.
• History of type I hypersensitivity, exfoliative rash, or rash with mucosal involvement, severe bronchospasm, or other life-threatening reaction to any of the study drugs or to other sulfas, sulfones, or pentamidine.
• History of intolerance causing dose interruption while receiving zidovudine at equal to or less than 500 mg/day with 4 weeks pior to study entry.

Prior Medication: Excluded within 4 weeks of study entry:

• Any other form of pneumocystosis (PCP) chemoprophylaxis.
• Active substance abuse, including alcohol.

California
      Univ of California / San Diego Treatment Ctr, San Diego,  California,  921036325,  United States
      Sepulveda Veterans Adm Med Ctr / Olive View Med Ctr, Sylmar,  California,  91342,  United States
      Stanford at Kaiser / Kaiser Permanente Med Ctr, San Francisco,  California,  94115,  United States
      San Francisco AIDS Clinic / San Francisco Gen Hosp, San Francisco,  California,  941102859,  United States
      Children's Hosp of Oakland, Oakland,  California,  946091809,  United States
      Stanford Private Practice, Redwood City,  California,  United States
      Stanford Univ School of Medicine, Stanford,  California,  94305,  United States
      UCSD Treatment Ctr, San Diego,  California,  92103,  United States
      Los Angeles County - USC Med Ctr, Los Angeles,  California,  90033,  United States
      Northern California Pediatric AIDS Treatment Ctr / UCSF, San Francisco,  California,  94143,  United States
District of Columbia
      George Washington Univ Med Ctr, Washington,  District of Columbia,  20037,  United States
      Whitman - Walker Clinic, Washington,  District of Columbia,  20009,  United States
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States
Illinois
      Chicago Children's Memorial Hosp, Chicago,  Illinois,  606143394,  United States
      Cook County Hosp, Chicago,  Illinois,  60612,  United States
      Rush Presbyterian - Saint Luke's Med Ctr, Chicago,  Illinois,  60612,  United States
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
Maryland
      Johns Hopkins Hosp, Baltimore,  Maryland,  21287,  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
      Baystate Med Ctr of Springfield, Springfield,  Massachusetts,  01199,  United States
      Univ of Massachusetts Med Ctr, Worcester,  Massachusetts,  01655,  United States
Minnesota
      Univ of Minnesota, Minneapolis,  Minnesota,  55455,  United States
New York
      SUNY / State Univ of New York, Syracuse,  New York,  13210,  United States
      SUNY - Stony Brook, Stony Brook,  New York,  117948153,  United States
      Jack Weiler Hosp / Bronx Municipal Hosp, Bronx,  New York,  10465,  United States
      Saint Luke's - Roosevelt Hosp Ctr, New York,  New York,  10025,  United States
      Montefiore Med Ctr / Bronx Municipal Hosp, Bronx,  New York,  10467,  United States
      SUNY / Erie County Med Ctr at Buffalo, Buffalo,  New York,  14215,  United States
      Beth Israel Med Ctr / Peter Krueger Clinic, New York,  New York,  10003,  United States
North Carolina
      Duke Univ Med Ctr, Durham,  North Carolina,  27710,  United States
Ohio
      Ohio State Univ Hosp Clinic, Columbus,  Ohio,  432101228,  United States
      Holmes Hosp / Univ of Cincinnati Med Ctr, Cincinnati,  Ohio,  452670405,  United States
      Univ Hosp of Cleveland / Case Western Reserve Univ, Cleveland,  Ohio,  44106,  United States
Pennsylvania
      Univ of Pittsburgh Med School, Pittsburgh,  Pennsylvania,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
Washington
      Univ of Washington, Seattle,  Washington,  98105,  United States

Study chairs or principal investigators

S Bozzette,  Study Chair
S Spector,  Study Chair

Study ID Numbers:  ACTG 081
Record last reviewed:  October 1994
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000991
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08