To evaluate the efficacy of AZT versus ddC in terms of survival, antiviral effects, neurological status, and health status in patients post Pneumocystis carinii pneumonia (PCP) who received long-term AZT therapy in ACTG protocol 002 While treatment with AZT has been found to be effective in prolonging survival and reducing the numbers of opportunistic infections in patients with AIDS, during the second year of administration of AZT an acceleration in mortality has been observed. The reasons for this are not known at this time. The study of what may be an AZT-resistant strain of HIV may benefit patients who have been and are still receiving AZT or another drug used in treating HIV ddC. It is hoped that the comparison of the effectiveness of AZT and ddC will benefit in the treatment of these patients.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Zidovudine  Drug: Zalcitabine	Phase III

Further Study Details: 

Expected Total Enrollment:  120

While treatment with AZT has been found to be effective in prolonging survival and reducing the numbers of opportunistic infections in patients with AIDS, during the second year of administration of AZT an acceleration in mortality has been observed. The reasons for this are not known at this time. The study of what may be an AZT-resistant strain of HIV may benefit patients who have been and are still receiving AZT or another drug used in treating HIV ddC. It is hoped that the comparison of the effectiveness of AZT and ddC will benefit in the treatment of these patients.

Following tests to evaluate their health, patients are chosen at random to receive either AZT or ddC. AZT is given by mouth at the patients' current dose. ddC is given by mouth every 8 hours. Treatment continues for up to 12 months. Patients are required to visit the clinic every 2 weeks up to week 12 and then once a month. Blood samples are taken to monitor the safety and effectiveness of treatment.

Ages Eligible for Study:  12 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Required:

• Prior zidovudine (AZT) therapy for 9 months. Concurrent Medication:

Allowed:

• Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP) with aerosolized pentamidine of 300 mg every 4 weeks through the Respirgard II nebulizer.
• Maintenance treatment with pyrimethamine, sulfadiazine, amphotericin, fluconazole, ketoconazole, acyclovir, or inhaled pentamidine for subjects who have recovered from toxoplasmosis, cryptococcosis, candidiasis, herpes infection, or PCP.
• Dapsone for PCP.
• Pyrimethamine-sulfadoxine for toxoplasmosis.
• Ganciclovir (DHPG) for maintenance only for cytomegalovirus (CMV) retinitis.
• Note: Any approved medications can be used to treat an opportunistic infection. All concurrent medications should be kept to a minimum and recorded.

Patients must be positive for HIV by ELISA test and must have been receiving zidovudine (AZT) therapy for at least 9 months and have received AZT within 90 days prior to entry into the study.

Patients may be transfusion dependent as long as no more than 3 units of blood are needed in a 21-day period and the hemoglobin does not fall below 6.4 g/dl on two consecutive occasions despite the transfusions.

Exclusion Criteria

Concurrent Medication: Excluded:

• Antiretroviral study medications other than zidovudine (AZT) and biologic response modifiers.
• Corticosteroids and chronic aspirin.
• Cimetidine.
• Flurazepam.
• Indomethacin.
• Ranitidine.
• Probenecid.
• Other experimental medications. Patients will be excluded from the study for the following reasons:
• Removal from zidovudine (AZT) during treatment on ACTG protocol 002 for recurrent grade 4 toxicity.
• Removal from prior dideoxycytidine (ddC) therapy for peripheral neuropathy = or > grade 3.
• Visceral or extensive Kaposi's sarcoma requiring therapy or another malignancy requiring therapy.
• Toxicity grades according to NIAID Recommendations for Grading Acute and Subacute Toxic Effects (Adults).

Prior Medication: Excluded:

• Antiretroviral study medications other than zidovudine (AZT) and biologic response modifiers.
• Patients may not have visceral or extensive Kaposi's sarcoma requiring therapy or another malignancy requiring therapy.

California
      Univ of California / San Diego Treatment Ctr, San Diego,  California,  921036325,  United States
      Los Angeles County - USC Med Ctr, Los Angeles,  California,  90033,  United States
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States
Illinois
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
Louisiana
      Charity Hosp / Tulane Univ Med School, New Orleans,  Louisiana,  70112,  United States
      Tulane Univ School of Medicine, New Orleans,  Louisiana,  70112,  United States
Maryland
      Johns Hopkins Hosp, Baltimore,  Maryland,  21287,  United States
Pennsylvania
      Univ of Pittsburgh Med School, Pittsburgh,  Pennsylvania,  United States
Washington
      Univ of Washington, Seattle,  Washington,  98105,  United States

Study chairs or principal investigators

Fischl M,  Study Chair
Richman D,  Study Chair
Murray H,  Study Chair

Study ID Numbers:  ACTG 112
Record last reviewed:  March 2003
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000682
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08