Hydroxyurea in combination with didanosine and stavudine in antiretroviral-experienced HIV-infected subjects with a review of the literature

Abstract

The safety and efficacy of hydroxyurea with didanosine in combination with stavudine in nucleoside reverse-transcriptase inhibitor (NRTI)-experienced patients was investigated. Entry criteria included HIV-1 infected, NRTI-experienced adults, with CD4⁺ counts 50-550 cells/mm³ and viral loads ≥12,500 copies/mL. Subjects were treated with didanosine 200 mg twice a day (BID), stavudine 40 mg BID, and hydroxyurea 1000 mg daily for 16 weeks. Thirty-one HIV-1 subjects with mean bDNA viral load 1×10⁵ log₁₀ copies/mL and mean CD4⁺ T-cell counts of 231 cells/mm³ were enrolled. A 1.3 log₁₀ decrease in mean viral load was seen at 12 weeks of therapy. Prior didanosine use resulted in a more rapid response to therapy compared with prior zidovudine use. Side effects consisting of neutropenia, pancreatitis, and peripheral neuropathy occurred in four subjects and resolved upon withdrawal of therapy. This non-randomized study in subjects with a mean CD4⁺ T-cell count of 230 cells/mm³ demonstrates the antiviral activity of hydroxyurea+didanosine and stavudine. Toxicities related to therapy need to be followed closely. The results support the need for a randomized, prospective study to determine the safety and efficacy of hydroxyurea plus didanosine in antiretroviral-experienced patients with CD4⁺ cell counts below 300 cells/mm³.