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NEUROLOGY 2009;72:165-170
© 2009 American Academy of Neurology

Benefits and risks of stavudine therapy for HIV-associated neurologic complications in Uganda

N. Sacktor, MD, N. Nakasujja, MB, ChB, R. L. Skolasky, ScD, K. Robertson, PhD, S. Musisi, FRCP, A. Ronald, MD, E. Katabira, FRCP and D. B. Clifford, MD, FAAN

From the Departments of Neurology (N.S.) and Orthopedic Surgery (R.L.S.), Johns Hopkins University School of Medicine, Baltimore, MD; Departments of Psychiatry (N.N., S.M.), and Medicine (E.K.), Makerere University, Kampala, Uganda; Department of Neurology (K.R.), University of North Carolina, Chapel Hill, NC; Department of Internal Medicine (A.R.), University of Manitoba, Winnipeg, Canada; and Department of Neurology (D.B.C.), Washington University, St. Louis, MO.

Address correspondence and reprint requests to Dr. Ned Sacktor, Department of Neurology, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, B Bldg. Rm. 123, Baltimore, MD 21224 sacktor{at}jhmi.edu

Background: The frequency of HIV dementia in a recent study of HIV+ individuals at the Infectious Disease Institute in Kampala, Uganda, was 31%. Coformulated generic drugs, which include stavudine, are the most common regimens to treat HIV infection in Uganda and many other parts of Africa.

Objective: To evaluate the benefits and risks of stavudine-based highly active antiretroviral therapy (HAART) for HIV-associated cognitive impairment and distal sensory neuropathy. The study compared neuropsychological performance changes in HIV+ individuals initiating HAART for 6 months and HIV– individuals receiving no treatment for 6 months. The risk of antiretroviral toxic neuropathy as a result of the initiation of stavudine-based HAART was also examined.

Methods: At baseline, 102 HIV+ individuals in Uganda received neurologic, neuropsychological, and functional assessments; began HAART; and were followed up for 6 months. Twenty-five HIV– individuals received identical clinical assessments and were followed up for 6 months.

Results: In HIV+ individuals, there was improvement in verbal memory, motor and psychomotor speed, executive thinking, and verbal fluency. After adjusting for differences in sex, HIV+ individuals demonstrated significant improvement in the Color Trails 2 test (p = 0.025) compared with HIV– individuals. Symptoms of neuropathy developed in 38% of previously asymptomatic HIV+ patients after initiation of the stavudine-based HAART.

Conclusions: After the initiation of highly active antiretroviral therapy (HAART) including stavudine, HIV+ individuals with cognitive impairment improve significantly as demonstrated by improved performance on a test of executive function. However, peripheral neurotoxicity occurred in 30 patients, presumably because of stavudine-based HAART, suggesting the need for less toxic therapy.

Abbreviations: AVLT = Auditory Verbal Learning Test; CES-D = Center for Epidemiologic Studies–Depression Scale; d-drug = dideoxynucleoside antiretroviral drug; GEE = generalized estimating equation; GP = Grooved Pegboard test; HAART = highly active antiretroviral therapy; HIV-SN = HIV-associated sensory neuropathy; IHDS = International HIV Dementia Scale; MSK = Memorial Sloan-Kettering; NA = not applicable; NS = not significant; SDMT = Symbol Digit Modalities Test; UCLA = University of California-Los Angeles; WHO = World Health Organization.

Supported by the Neurologic AIDS Research Consortium, which receives support from the National Institute of Neurological Diseases and Stroke (NS 32228), and MH71150.

Disclosure: The authors report no disclosures.

Received June 5, 2008. Accepted in final form October 1, 2008.