Biomaterial Database

Alternating and intermittent regimens of zidovudine and dideoxycytidine in patients with AIDS or AIDS-related complex. 1993

G Skowron, and S A Bozzette, and L Lim, and C B Pettinelli, and H H Schaumburg, and J Arezzo, and M A Fischl, and W G Powderly, and D J Gocke, and D D Richman, and J C Pottage, and D Antoniskis, and G F McKinley, and N E Hyslop, and G Ray, and G Simon, and N Reed, and M L LoFaro, and R B Uttamchandani, and L D Gelb, and S J Sperber, and R L Murphy, and J M Leedom, and M H Grieco, and J Zachary, and M S Hirsch, and S A Spector, and J Bigley, and W Soo, and T C Merigan

Division of Infectious Diseases, Roger Williams Hospital, Providence, RI 02908.

OBJECTIVE To determine whether alternating regimens consisting of zidovudine and 2',3'-dideoxycytidine (ddC) reduce the toxicity and maintain or increase the antiretroviral effect associated with each drug alone. METHODS An unblinded, randomized (phase II) clinical trial in which seven treatment regimens were compared. METHODS Outpatient clinics of 12 AIDS Clinical Trials Units. METHODS One hundred thirty-one patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and serum p24 antigenemia (> or = 70 pg/mL). METHODS Treatments included weekly or monthly alternating zidovudine (200 mg every 4 hours) and ddC (0.01 or 0.03 mg/kg body weight every 4 hours); weekly intermittent zidovudine, 200 mg every 4 hours, or ddC, 0.03 mg/kg every 4 hours; and continuous zidovudine. METHODS Toxicity, CD4 cell counts, serum p24 antigen levels, and clinical end points. Data were analyzed for the first 48 weeks of therapy (median follow-up, 40 weeks). RESULTS Hematologic toxicity was significantly less frequent in patients who received zidovudine therapy every other week (11% to 15%) or every other month (11% to 14%) than in those who received continuous zidovudine therapy (33%) (P < 0.02). Weekly alternating therapy with zidovudine and ddC, 0.03 mg/kg, or intermittent therapy with ddC, 0.03 mg/kg, produced high rates of peripheral neuropathy (41% and 50%, respectively). Neuropathy occurred in 10% to 21% of patients in the other three alternating-therapy limbs and in 17% of patients receiving zidovudine alone (intermittently or continuously). Initial increases in CD4 cell counts were sustained in three alternating-therapy limbs, but counts returned to baseline by week 28 in the remaining limbs. The median weight gain at week 48 was significantly greater in patients treated with alternating regimens (0.9 to 3.8 kg) compared with those treated with continuous zidovudine therapy (-0.7 kg) (P = 0.008). Patients treated with alternating regimens and those treated with continuous zidovudine had similarly sustained decreases in p24 antigen levels. CONCLUSIONS These findings suggest that alternating therapy with zidovudine and ddC reduces the toxicity associated with each drug alone while maintaining strong antiretroviral activity.

UI	MeSH Term	Description	Entries
D007958	Leukocyte Count	The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells.	Blood Cell Count, White,Differential Leukocyte Count,Leukocyte Count, Differential,Leukocyte Number,White Blood Cell Count,Count, Differential Leukocyte,Count, Leukocyte,Counts, Differential Leukocyte,Counts, Leukocyte,Differential Leukocyte Counts,Leukocyte Counts,Leukocyte Counts, Differential,Leukocyte Numbers,Number, Leukocyte,Numbers, Leukocyte
D008297	Male		Males
D010523	Peripheral Nervous System Diseases	Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.	Peripheral Nerve Diseases,Peripheral Neuropathies,PNS (Peripheral Nervous System) Diseases,PNS Diseases,Peripheral Nervous System Disease,Peripheral Nervous System Disorders,Nerve Disease, Peripheral,Nerve Diseases, Peripheral,Neuropathy, Peripheral,PNS Disease,Peripheral Nerve Disease,Peripheral Neuropathy
D004334	Drug Administration Schedule	Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.	Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D004359	Drug Therapy, Combination	Therapy with two or more separate preparations given for a combined effect.	Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D005260	Female		Females
D006402	Hematologic Diseases	Disorders of the blood and blood forming tissues.	Blood Diseases,Hematological Diseases,Blood Disease,Disease, Blood,Disease, Hematologic,Disease, Hematological,Diseases, Blood,Diseases, Hematologic,Diseases, Hematological,Hematologic Disease,Hematological Disease
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000163	Acquired Immunodeficiency Syndrome	An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993.	AIDS,Immunodeficiency Syndrome, Acquired,Immunologic Deficiency Syndrome, Acquired,Acquired Immune Deficiency Syndrome,Acquired Immuno-Deficiency Syndrome,Acquired Immuno Deficiency Syndrome,Acquired Immuno-Deficiency Syndromes,Acquired Immunodeficiency Syndromes,Immuno-Deficiency Syndrome, Acquired,Immuno-Deficiency Syndromes, Acquired,Immunodeficiency Syndromes, Acquired,Syndrome, Acquired Immuno-Deficiency,Syndrome, Acquired Immunodeficiency,Syndromes, Acquired Immuno-Deficiency,Syndromes, Acquired Immunodeficiency
D000386	AIDS-Related Complex	A prodromal phase of infection with the human immunodeficiency virus (HIV). Laboratory criteria separating AIDS-related complex (ARC) from AIDS include elevated or hyperactive B-cell humoral immune responses, compared to depressed or normal antibody reactivity in AIDS; follicular or mixed hyperplasia in ARC lymph nodes, leading to lymphocyte degeneration and depletion more typical of AIDS; evolving succession of histopathological lesions such as localization of Kaposi's sarcoma, signaling the transition to the full-blown AIDS.	ARC,Lymphadenopathy Syndrome,AIDS Related Complex,Complex, AIDS-Related,Lymphadenopathy Syndromes,Syndrome, Lymphadenopathy,Syndromes, Lymphadenopathy