A Trial of Alternating 2',3'-Dideoxycytidine and Zidovudine in the Treatment of Patients With Advanced HIV Disease

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Aug 30, 2001

Keywords

ClinConnect Summary

AIDS is a serious infectious disease caused by a new family of retrovirus which is spread primarily through sexual contact and administration of blood or blood products. Individuals who are infected with HIV could therefore benefit from therapy with an effective anti-AIDS virus agent. AZT and ddC have both been tested as antiviral agents and their potentially beneficial effects may be limited by time- and dose-dependent toxicity. A combination regimen using shorter courses of AZT and ddC might therefore be able to sustain treatment without producing toxicity. In addition, since the two drug...

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Eligibility criteria

• • Inclusion Criteria
• Concurrent Medication:
• Allowed:
• • Aerosolized pentamidine at prophylactic doses, but its use is discouraged in persons without a history of Pneumocystis carinii pneumonia (PCP).
• • Acyclovir for acute disseminated zoster.
• • Maintenance doses of pyrimethamine, amphotericin, and pentamidine are allowed for patients who recover from toxoplasmosis, cryptococcosis, or pneumocystosis acquired after study entry.
• • Patients included in the study must have HIV infection confirmed by ELISA test and must have a documented history of at least 4 weeks of zidovudine (AZT) treatment.
• * While hemoglobin at the start of AZT therapy must have been = or \> 9.5 g/dl and granulocyte count = or \> 1200 cells/mm3 at the start of AZT therapy, hematologic toxicity due to a reduced dose of AZT will be defined as:
• • Hematologic toxicity must have occurred during a period when AZT was administered at = or \< 600 mg/day for at least 2 weeks.
• • There must have been no evidence of a cause for toxicity other than HIV infection and AZT use.
• • Hematologic intolerance may have consisted of hemoglobin toxicity, granulocyte toxicity, or both.
• • Recovery from hematologic toxicity must be manifested by the presence of a granulocyte count of \> 1000 cells/mm3 and a hemoglobin of \> 9.5 g/dl. without transfusions during the preceding 4 weeks. Patients must also have no significant bilateral symptoms of peripheral neuropathy, although all patients may have any degree of stable unilateral neurologic deficit. Up to 24 patients may have certain moderate bilateral abnormalities of peripheral neuropathy. AZT may not have been administered within 14 days prior to entering the study.
• Prior Medication:
• Required:
• • A documented history of at least 4 weeks of zidovudine treatment which resulted in hematologic toxicity at reduced dose.
• * Allowed but discouraged:
• • A1-721.
• • Exclusion Criteria
• Co-existing Condition:
• Patients with the following are excluded:
• • Known active AIDS opportunistic infections.
• • Known mycobacteremia, although cultures may be pending at the time of enrollment.
• • Symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to entry into the study or with concurrent neoplasms other than KS, basal cell carcinoma of the skin or in situ carcinoma of the cervix.
• • Significant malabsorption as manifested by steatorrhea with greater than 10 percent weight loss within the last 3 months.
• • Diabetes.
• Concurrent Medication:
• Excluded:
• • Experimental medications.
• • Aspirin.
• • Acetaminophen.
• • Nonsteroidal anti-inflammatory agents should be minimized, with continuous use for \> 72 hours discouraged.
• • Chronic suppressive anti-infective therapy other than inhaled pentamidine and neurotoxic drugs should be avoided.
• • Continuous therapy for \> 7 days of acyclovir is prohibited except for the acute treatment of disseminated herpes zoster infection.
• Patients with the following are excluded:
• • Known mycobacteremia, although cultures may be pending at the time of enrollment.
• • Symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to entry into the study or with concurrent neoplasms other than KS, basal cell carcinoma of the skin or in situ carcinoma of the cervix.
• • Significant malabsorption as manifested by steatorrhea with greater than 10 percent weight loss within the last 3 months.
• • Diabetes.
• • Known active AIDS opportunistic infections. Patients must also have no significant bilateral symptoms of peripheral neuropathy, although all patients may have any degree of stable unilateral neurologic deficit. Up to 24 patients may have certain moderate bilateral abnormalities of peripheral neuropathy. AZT may not have been administered within 14 days prior to entering the study.
• Prior Medication:
• Excluded within 30 days of study entry:
• • Any antiretroviral agents except zidovudine (AZT).
• * Discouraged:
• • A1-721.
• • Pentamidine at prophylactic doses in persons without a history of Pneumocystis carinii pneumonia (PCP).
• • Active substance and/or alcohol abuse.

Trial Officials