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In Vivo ActivityAgainst HIV andFavorable ToxicityProfile of2′,3′-Dideoxyinosine Robert YarchoanHiroaki MitsuyaRose V. Thomas1989 год

In Vivo Activity Against HIV and Favorable Toxicity Profile of 2′,3′-Dideoxyinosine
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Аннотация: The purine analog 2′,3′-dideoxyinosine (ddI), which has anti-retroviral activity in vitro was administered for up to 42 weeks to 26 patients with acquired immunodeficiency syndrome (AIDS) or severe AIDS-related complex (ARC). Ten of these individuals were AZT-intolerant. Eight dose regimens were studied. The drug was orally bioavailable and penetrated into the cerebrospinal fluid (CSF). Comparatively little evidence of an effect against human immunodeficiency virus (HIV) was seen at the lowest four doses. However, patients in the four highest dose groups (ddI at 1.6 milligrams per kilogram intravenously and then ≥ 3.2 milligrams per kilogram orally at least every 12 hours or higher) had increases in their circulating CD4 + T cells (P < 0.0005), increased CD4/CD8 T cell ratios (P < 0.01), and, where evaluable, more than an 80% decrease in serum HIV p24 antigen (P < 0.05). The patients also had evidence of improved immunologic function, had reduced viremic symptomatology, and gained a mean of 1.6 kilogram with these comparatively infrequent dosing schedules (every 8 or 12 hours). The most notable adverse effects directly attributable to ddI administration at the doses used in this study included increases in serum uric acid (due to hypoxanthine release) and mild headaches and insomnia. These results suggest that serious short-term toxicity at therapeutic doses is not an inherent feature in the profile of agents with clinical anti-HIV activity. Further controlled studies to define the safety and efficacy of this agent may be worth considering.
Год издания: 1989
Авторы: Robert Yarchoan, Hiroaki Mitsuya, Rose V. Thomas, James M. Pluda, Neil R. Hartman, Carlo Federico Perno, Kathy S. Marczyk, Jean‐Pierre Allain, David G. Johns, Samuel Broder
Издательство: American Association for the Advancement of Science
Источник: Science
Ключевые слова: HIV Research and Treatment, HIV/AIDS drug development and treatment, Pneumocystis jirovecii pneumonia detection and treatment
Другие ссылки: Science (HTML)
Zenodo (CERN European Organization for Nuclear Research) (PDF)
Zenodo (CERN European Organization for Nuclear Research) (HTML)
PubMed (HTML)