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Intermittent Administration of High-Dose Stavudine to Nucleoside-Experienced Individuals Infected With HIV-1

Acosta Edward P.; Balfour, Henry H. Jr.
JAIDS Journal of Acquired Immune Deficiency Syndromes: July 1st, 2003

To explore a novel method to use nucleosides in heavily treated patients, 4-week cycles of high-dosage (280 mg/d) stavudine were given to 11 asymptomatic patients who had previously received an average of 6 years of nucleoside reverse transcriptase inhibitors (NRTIs). The stavudine dose was targeted to produce a calculated steady-state concentration of 1.5 μM (336 ng/mL). Participants received stavudine for the first 4 weeks, after which it was discontinued for 4 weeks. Additional 4-week drug cycles were given if plasma HIV-1 RNA levels increased to at least 75% of baseline values. The 11 subjects received 38 cycles (average, 3.5 cycles per subject) during the 44-week study. Stavudine was well tolerated. Considering all data, there was a median 0.65 log10 reduction in viral load as well as a median increase in CD4 cell count of 110/mm3 at the end of the cycles. However, plasma viremia increased and CD4 cell counts decreased between cycles. Viral load and CD4 cell responses were similar for up to 4 successive cycles. This suggested that increasing viral resistance was not a problem, as reflected by the acquisition of only one new nucleoside reverse transcriptase mutation among the participants. Significant relationships between stavudine exposure and changes in plasma HIV RNA levels were observed. A similar approach might be considered using a more potent regimen for patients in whom resistance to nucleosides is a major reason for therapeutic failure.

Supported in part by grants UO1-AI38858 and AI27661 from the National Institute of Allergy and Infectious Diseases, the University of Minnesota International Center for Antiviral Research and Epidemiology, and the Minnesota Medical Foundation.

Address correspondence and reprint requests to Henry H. Balfour, Jr., MD, MMC437, 420 Delaware Street SE, Minneapolis, MN 55455. E-mail:

Manuscript received January 14, 2003; accepted March 19, 2003.

© 2003 Lippincott Williams & Wilkins, Inc.