Official Title: “A Randomized Trial of Three Anti-Pneumocystis Agents Plus Zidovudine for the Primary Prevention of Serious Infections in Patients With Advanced HIV Infection”

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.

Study Type: Interventional

Study Design: Treatment, Open Label

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.

Intervention(s) in this Clinical Trial

• Drug: Pentamidine isethionate
• Drug: Sulfamethoxazole-Trimethoprim
• Drug: Dapsone
• Drug: Zidovudine

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 13 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Overall Clinical Trial Officials and Contacts

S Bozzette Study Chair   

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00000991

Study ID Number: ACTG 081

ClinicalTrials.gov Identifier: NCT00000991

Health Authority: United States: Federal Government

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