Once-daily administration of 2',3'-dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex. Results of a Phase I trial. 1990

T P Cooley, and L M Kunches, and C A Saunders, and J K Ritter, and C J Perkins, and C McLaren, and R P McCaffrey, and H A Liebman
Department of Medicine, Boston City Hospital, MA 02118.

We conducted a Phase I open-label trial of 2',3'-dideoxyinosine (ddI) for the treatment of the acquired immunodeficiency syndrome (AIDS) and severe AIDS-related complex. A single daily dose of ddI was administered orally to 34 patients (17 with AIDS and 17 with AIDS-related complex) for a median of 12 weeks (range, 2 to 56). We studied six dose levels from 1.6 to 30.4 mg per kilogram of body weight per day. Of the 17 patients previously treated with zidovudine, 13 had had hematologic side effects. The maximal tolerated dose of oral ddI was estimated to be 20.4 mg per kilogram per day. Pancreatitis and peripheral neuropathy were the major dose-limiting toxic effects. Other toxic effects included elevations in hepatic transaminase levels, abnormalities in cardiac conduction, rash, and asymptomatic elevations in serum urate levels and the creatine kinase fraction from skeletal muscle. Treatment with ddI was associated with an increase in the mean number of CD4 lymphocytes from 125 per cubic millimeter at base line to 182 per cubic millimeter after 10 weeks (P = 0.005). There were also increases after 12 weeks in the mean total lymphocyte count (from 0.8 to 1.2 x 10(9) per liter) and the mean hemoglobin level (from 12.9 to 14.1 g per deciliter) (both P less than 0.01). The amount of human immunodeficiency virus p24 antigen decreased by more than 50 percent in 14 of 19 patients with detectable antigen. No differences in response were observed between patients previously treated with zidovudine and those never treated with the drug. We conclude that ddI has antiretroviral activity in patients with AIDS or AIDS-related complex and that the toxicity of ddI differs from that of zidovudine. However, controlled trials are necessary to evaluate the efficacy of ddI.

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
D004341 Drug Evaluation Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals. Evaluation Studies, Drug,Drug Evaluation Studies,Drug Evaluation Study,Drug Evaluations,Evaluation Study, Drug,Evaluation, Drug,Evaluations, Drug,Studies, Drug Evaluation,Study, Drug Evaluation
D004361 Drug Tolerance Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL. Drug Tolerances,Tolerance, Drug,Tolerances, Drug
D005260 Female Females
D006377 T-Lymphocytes, Helper-Inducer Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions. Helper Cell,Helper Cells,Helper T Cell,Helper-Inducer T-Lymphocytes,Inducer Cell,Inducer Cells,T-Cells, Helper-Inducer,T-Lymphocytes, Helper,T-Lymphocytes, Inducer,Helper T-Cells,Cell, Helper T,Cells, Helper T,Helper Inducer T Lymphocytes,Helper T Cells,Helper T-Cell,Helper T-Lymphocyte,Helper T-Lymphocytes,Helper-Inducer T-Cell,Helper-Inducer T-Cells,Helper-Inducer T-Lymphocyte,Inducer T-Lymphocyte,Inducer T-Lymphocytes,T Cell, Helper,T Cells, Helper,T Cells, Helper Inducer,T Lymphocytes, Helper,T Lymphocytes, Helper Inducer,T Lymphocytes, Inducer,T-Cell, Helper,T-Cell, Helper-Inducer,T-Cells, Helper,T-Lymphocyte, Helper,T-Lymphocyte, Helper-Inducer,T-Lymphocyte, Inducer
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
D015488 HIV Antigens Antigens associated with specific proteins of the human adult T-cell immunodeficiency virus (HIV); also called HTLV-III-associated and lymphadenopathy-associated virus (LAV) antigens. AIDS Antigens,HIV-Associated Antigens,HTLV-III Antigens,HTLV-III-LAV Antigens,LAV Antigens,Lymphadenopathy-Associated Antigens,T-Lymphotropic Virus Type III Antigens, Human,HIV Associated Antigens,HTLV III Antigens,HTLV III LAV Antigens,Lymphadenopathy Associated Antigens,T Lymphotropic Virus Type III Antigens, Human,Antigens, AIDS,Antigens, HIV,Antigens, HIV Associated,Antigens, HIV-Associated,Antigens, HTLV III,Antigens, HTLV-III,Antigens, HTLV-III-LAV,Antigens, LAV,Antigens, Lymphadenopathy Associated,Antigens, Lymphadenopathy-Associated,Associated Antigens, HIV,Associated Antigens, Lymphadenopathy,III Antigens, HTLV

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