Zidovudine Toxicity

Abstract

Zidovudine is a dideoxynucleoside analogue of thymidine. It acts by interfering with viral reverse transcriptase, thereby inhibiting human immunodeficiency virus (HIV) replication. Zidovudine has been shown in clinical trials to prolong survival of patients with acquired immune deficiency syndrome (AIDS) and advanced AIDS-related complex (ARC), and to delay progression to ARC or AIDS in patients with earlier disease. At the present time it is suggested that zidovudine be initiated when the CD4 lymphocyte count is less than 500 cells/mm3. Recent studies have suggested a delay in the development of AIDS in patients with CD4 counts over 500 cells/mm3, but ongoing studies will require confirmation. The adverse reactions associated with zidovudine have been well described. It appears that haematological toxicity is associated with both the dose and stage of disease. Anaemia may present more often within the first 3 months of therapy, whereas neutropenia can occur early or late. Mild headache and gastrointestinal intolerance may occur early and in some cases limit tolerance to the drug. A number of neurological adverse reactions have been reported rarely including seizures and dose-reduction encephalopathy. The most significant late adverse reaction is that of myopathy, which occurs in patients receiving zidovudine for more than 6 months. With careful monitoring, the adverse reactions of zidovudine are manageable and patient tolerance of the medication is acceptable.

A Clinical Metabolite of Azidothymidine Inhibits Experimental Choroidal Neovascularization and Retinal Pigmented Epithelium Degeneration

“… 7 , 8 However, the systemic toxicity associated with AZT makes it less than ideal as a repurposing drug candidate for AMD. 9 This toxicity is associated directly with its ability to inhibit reverse transcriptase, an activity necessary for its anti-retroviral function but unessential for its anti-inflammatory activity. 10 – 12 Hence, identification of AZT analogs that lack the ability to inhibit reverse transcriptase and assessing the anti-inflammatory and anti-angiogenic properties of these analogs may help identify potential drug candidates for AMD.…”

Partial recovery of disturbed V-J pairing profiles of T-cell receptor in people living with HIV receiving long-term antiretroviral therapy

“…+ T cells, which may drives the interindividual similarity even far away from the normal status. It has been reported that zidovudine, a nucleoside analogue, can cause myelosuppression and can inhibit lymphocyte development (Rachlis and Fanning, 1993). Whether other drugs might affect TCR V-J paring requires further studies with clinical cohort or animal experiments.…”

Evidence for risk stratification when monitoring for toxicities following initiation of combination antiretroviral therapy

“…Hypertension, a risk factor for renal abnormalities in the current study, is a well known predictor of chronic kidney disease in both HIV-infected and HIV-uninfected populations [19,20]. The hematologic side-effect profile of ZDV was well described by the early 1990s [21], although a more recent study suggested a weaker link between ZDV and anemia in the cART era [22]. In our study, ZDV use was associated with hematologic abnormalities, but this effect extended only through the first 16 weeks of therapy suggesting that ZDV use alone may not justify intensive hematologic monitoring indefinitely.…”