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Frequency of stavudine substitution due to toxicity in children receiving antiretroviral treatment in sub-Saharan Africa

Palmer, Megana; Chersich, Matthewb,c; Moultrie, Harrye; Kuhn, Louised; Fairlie, Leee; Meyers, Tammya

doi: 10.1097/QAD.0b013e32835c54b8
Clinical Science: Concise Communication

Introduction: Stavudine is a commonly used drug in paediatric antiretroviral treatment (ART) regimens. Due to toxicity concerns, however, the drug abacavir has replaced stavudine in first-line paediatric regimens in many countries. We describe the frequency of stavudine toxicity in children receiving ART at a treatment clinic in Soweto, South Africa.

Methods: Data on patient characteristics and outcomes of ART were collected from a cohort of 2222 HIV-infected children initiating ART between 2004 and 2008 when stavudine-containing regimens were routinely recommended. At several time-points after treatment initiation, we estimate the proportion of children where an attending clinician discontinued stavudine due to lipodystrophy, pancreatitis, lactic acidosis or peripheral neuropathy. Factors associated with stavudine-related toxicities were identified.

Results: At ART initiation, most children had advanced disease. The majority initiated an efavirenz/lamivudine/stavudine regimen (n = 1422), and 76% of children remained on their initial ART regimen after a median 19.9 months of ART. Replacement of stavudine due to drug toxicity occurred at a rate of 28.8 per 1000 child years on treatment (95% confidence interval = 23.6–35.2). Rates of toxicity increased with treatment duration (in their first year of ART stavudine was replaced in 0.5% of children, but after 3 years stavudine had been changed to abacavir in 12.6% of children). Toxicity was more common in older children and in girls. Lipodystrophy accounted for 87 of 96 toxic events.

Conclusion: Stavudine-associated toxicity resulting in single-drug substitution was uncommon in this cohort, though its frequency increased steadily with ART duration, especially with lipodystrophy. Where drug options are limited, stavudine remains a relatively well tolerated and effective option for children.

aDepartment of Paediatrics, Chris Hani Baragwanath Hospital, Faculty of Health Sciences

bCentre for Health Policy, School of Public Health, University of Witwatersrand, Johannesburg, South Africa

cInternational Centre for Reproductive Health, Department of Obstetrics and Gynaecology, Ghent University, Ghent, Belgium

dGertrude H. Sergievsky Center, College of Physicians and Surgeons; and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA

eWits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Correspondence to Tammy Meyers, Department of Paediatrics Chris Hani Baragwanath Hospital, PO Bertsham, Johannesbug, South Africa. E-mail:

Received 11 October, 2011

Revised 26 October, 2012

Accepted 6 November, 2012

© 2013 Lippincott Williams & Wilkins, Inc.