The Toxicity of Azidothymidine (AZT) in the Treatment of Patients with AIDS and AIDS-Related Complex

Abstract

We conducted a double-blind, placebo-controlled trial of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Although significant clinical benefit was documented (N Engl J Med 1987; 317:185-91), serious adverse reactions, particularly bone marrow suppression, were observed. Nausea, myalgia, insomnia, and severe headaches were reported more frequently by recipients of AZT; macrocytosis developed within weeks in most of the AZT group. Anemia with hemoglobin levels below 7.5 g per deciliter developed in 24 percent of AZT recipients and 4 percent of placebo recipients (P less than 0.001). Twenty-one percent of AZT recipients and 4 percent of placebo recipients required multiple red-cell transfusions (P less than 0.001). Neutropenia (less than 500 cells per cubic millimeter) occurred in 16 percent of AZT recipients, as compared with 2 percent of placebo recipients (P less than 0.001). Subjects who entered the study with low CD4 lymphocyte counts, low serum vitamin B12 levels, anemia, or low neutrophil counts were more likely to have hematologic toxic effects. Concurrent use of acetaminophen was also associated with a higher frequency of hematologic toxicity. Although a subset of patients tolerated AZT for an extended period with few toxic effects, the drug should be administered with caution because of its toxicity and the limited experience with it to date.

Preparation and antiherpetic activities of chemically modified polysaccharides from Polygonatum cyrtonema Hua

“…Unlike the widely used acyclovir (ACV)-related nucleoside analogues, which all targeted against viral DNA synthesis, polysaccharides interfere with the attachment of virus to host cell surface by binding to viral envelope glycoprotein (Damonte et al, 2004;Duarte et al, 2001;Neyts et al, 1992;Witvrouw & De Clercq, 1997). In contrast with ACV, which may result in some undesirable complications (Richman et al, 1987) and also induce the emergence of drugresistant viruses (Coen, 1991;Larder, Darby, & Richman, 1989) after prolonged treatment in immunocompromised patients, polysaccharides have the relatively low mammalian toxicity and the novel * Corresponding author. Tel.…”

Continuous and Discontinuous Changes in the Unit Cell of HIV-1 Reverse Transcriptase Crystals on Dehydration

“…The effectiveness of anti-AIDS therapies is compromised by the selection for drugresistant viral populations (Larder & Kemp, 1989;Schinazi et al, 1996). Drug resistance and the presence of serious side-effects associated with some therapies (Richman et al, 1987) make the search for new drugs and better ways of combining the use of existing drugs the focus of intensive research, one component of which is structural analysis.…”

Potent and selective activity of a new carbocyclic nucleoside analog (Carbovir: NSC 614846) against human immunodeficiency virus In vitro

“…Early clinical results with ddC have indicated therapeutic activity, but also some undesirable side effects (e.g., peripheral neuropathy) (7). It should also be noted that AZT, while clinically useful in many settings, also is associated with substantial toxicity, especially myelosuppression (8).…”