Open Access Highly Accessed Research article

A longitudinal study of stavudine-associated toxicities in a large cohort of South African HIV infected subjects

Colin N Menezes123*, Mhairi Maskew23, Ian Sanne23, Nigel J Crowther4 and Frederick J Raal5

Author Affiliations

1 Infectious Diseases Unit, Department of Medicine, Helen Joseph Hospital, University of the Witwatersrand, Johannesburg, South Africa

2 Clinical HIV Research Unit, Helen Joseph Hospital, University of the Witwatersrand, Johannesburg, South Africa

3 Themba Lethu Clinic, Helen Joseph Hospital, Johannesburg, South Africa

4 Department of Chemical Pathology, National Health Laboratory Service and University of the Witwatersrand, Johannesburg, South Africa

5 Division of Endocrinology & Metabolism, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa

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BMC Infectious Diseases 2011, 11:244  doi:10.1186/1471-2334-11-244

Published: 17 September 2011



There has been major improvement in the survival of HIV-1 infected individuals since the South African Government introduced highly active anti-retroviral therapy (HAART) in the public sector in 2004. This has brought new challenges which include the effects of stavudine-related toxicities.


Prospective analysis of a cohort of 9040 HIV-infected adults who were initiated on HAART at the Themba Lethu Clinic (TLC) in Johannesburg between April 1, 2004 to December 31, 2007, and followed up until June 30, 2008.


Amongst the 9040 study subjects, 8497(94%) were on stavudine based therapy and 5962 (66%) were women. The median baseline CD4 count was 81 cells/mm3 (IQR 29-149). Median follow up on HAART was 19 months (IQR: 9.1-31.6). The proportion of HAART-related side effects for stavudine compared to non-stavudine containing regimens were, respectively: peripheral neuropathy,17.1% vs. 11.2% (p < 0.001); symptomatic hyperlactataemia, 5.7% vs. 2.2% (p < 0.0005); lactic acidosis, 2.5 vs. 1.3% (p = 0.072); lipoatrophy, 7.3% vs. 4.6% (p < 0.05). Among those on stavudine-based regimens, incidence rates for peripheral neuropathy were 12.1 cases/100 person-years (95%CI 7.0-19.5), symptomatic hyperlactataemia 3.6 cases/100 person-years (95%CI 1.2-7.5), lactic acidosis 1.6 cases/100 person-years (95%CI 0.4-5.2) and lipoatrophy 4.6 cases/100 person-years (95%CI 2.1-9.6). Females experienced more toxicity when compared to males in terms of symptomatic hyperlactataemia (p < 0.0001), lactic acidosis (p < 0.0001), lipoatrophy (p < 0.0001) and hypertension (p < 0.05).


We demonstrate significant morbidity associated with stavudine. These data support the latest WHO guidelines, and provide additional evidence for other resource limited HAART rollout programs considering the implementation of non-stavudine based regimens as first line therapy.