Open AccessIntermittent Administration of High-Dose Stavudine to Nucleoside-Experienced Individuals Infected With HIV-1
Author(s) -
Edward P. Acosta,
Henry H. Balfour
Publication year - 2003
Publication title -
journal of acquired immune deficiency syndromes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.162
H-Index - 157
eISSN - 1944-7884
pISSN - 1525-4135
DOI - 10.1097/00126334-200307010-00008
Subject(s) - stavudine , regimen , didanosine , reverse transcriptase inhibitor , nucleoside reverse transcriptase inhibitor , viremia , reverse transcriptase , viral load , medicine , nucleoside , nucleoside analogue , asymptomatic , drug resistance , human immunodeficiency virus (hiv) , virology , pharmacology , immunology , gastroenterology , biology , rna , antiretroviral therapy , biochemistry , microbiology and biotechnology , gene
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 microM (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 log(10) 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.