The risk of developing peripheral neuropathy induced by nucleoside reverse transcriptase inhibitors decreases over time : evidence from the Delta trial

Peripheral neuropathy (PN) in HIV-infected individuals is thought be due to a toxic effect on mitochondria induced by some nucleoside reverse transcriptase inhibitors (NRTI). A time-to-event analysis was performed using data from the Delta trial to study the incidence of PN in HIV-infected individua...

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Bibliographic Details
Published in:Antiviral therapy 2008-01, Vol.13 (2), p.289-295
Main Authors: ARENAS-PINTO, Alejandro, BHASKARAN, Krishnan, DUNN, David, WELLER, Lan V. D
Format: Article
Language:English
Subjects:
Adult
Anti-HIV Agents - adverse effects
Anti-HIV Agents - therapeutic use
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Biological and medical sciences
Didanosine - adverse effects
Didanosine - therapeutic use
Double-Blind Method
Drug Therapy, Combination
Female
HIV Infections - complications
HIV Infections - drug therapy
HIV Infections - virology
Human immunodeficiency virus
Humans
Incidence
Male
Medical sciences
Middle Aged
Peripheral Nervous System Diseases - chemically induced
Peripheral Nervous System Diseases - epidemiology
Pharmacology. Drug treatments
Reverse Transcriptase Inhibitors - adverse effects
Reverse Transcriptase Inhibitors - therapeutic use
Risk Factors
Time Factors
Zalcitabine - adverse effects
Zalcitabine - therapeutic use
Zidovudine - adverse effects
Zidovudine - therapeutic use
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Summary:Peripheral neuropathy (PN) in HIV-infected individuals is thought be due to a toxic effect on mitochondria induced by some nucleoside reverse transcriptase inhibitors (NRTI). A time-to-event analysis was performed using data from the Delta trial to study the incidence of PN in HIV-infected individuals receiving zidovudine (AZT) alone or in combination with didanosine (ddl) or zalcitabine (ddC). In an on-treatment analysis, changes in the incidence of PN by duration of treatment were directly estimated using a flexible parametric survival model. A total of 3,195 patients (total follow-up 4,593 person-years) were included in the analysis. AZT+ddC was associated with a higher incidence of PN (6.2 cases/100 person-years) compared with AZT monotherapy (3.0 cases/100 person-years) and AZT+ddl (2.2 cases/100 person-years). The risk of PN peaked around day 90 following randomization (at 8.9 events/100 person-years in the AZT+ddC arm). PN was also associated with age at entry (hazard ratio (HR)=2.35 for those aged 35-44 years compared with
ISSN:1359-6535
2040-2058
DOI:10.1177/135965350801300203