Lowering the dose of hydroxyurea minimizes toxicity and maximizes anti-HIV potency

Franco Lori, Richard B Pollard, L. Whitman, N. Bakare, G. Blick, P. Shalit, A. Foli, D. Peterson, A. Tennenberg, S. Schrader, B. Rashbaum, C. Farthing, D. Herman, D. Norris, P. Greiger, I. Frank, A. Groff, L. Lova, David Asmuth, J. Lisziewicz

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The goal of this study was to optimize the hydroxyurea dosage in HIV-infected patients, and to minimize the toxicity and maximize the antiviral efficacy of the hydroxyurea-didanosine combination. In a randomized, open-label study (RIGHT 702, a multicenter trial performed in private and institutional practices), three daily doses (600 μg, 800-900 μg, and 1200 μg) of hydroxyurea were administered in combination with didanosine and stavudine to 115 chronically HIV-infected patients, one-third antiretroviral drug naive, with viremia between 5000 and 200,000 copies/ml regardless of CD4+ cell count. The primary efficacy end point was the proportion of patients with plasma HIV-1 RNA levels below 400 copies/ml after 24 weeks of therapy. In the RIGHT 702 intent-to-treat population the lowest (600 mg) dose of hydroxyurea was better tolerated, associated with fewer adverse events, and more potent by all efficacy parameters, including the primary end point (76 versus 60% patients with viremia < 400 copies/ml at week 24 for the 600-mg and 800- to 900-mg dose groups, respectively; p = 0.027), the mean area under the curve (60.3 versus 65.8; p = 0.016), and the mean log10 decrease (-1.95 versus -0.77; p = 0.001). Patients receiving 600 mg of hydroxyurea daily also had the highest CD4+ cell count, CD4+/CD8+ cell ratio, and lowest CD8+ cell count and percentage (p = 0.035). The RIGHT 702 trial provides an explanation for the increased toxicity and decreased efficacy of hydroxyurea when it was used at high dosage (1200 mg daily). At the optimal dosage of 600 mg daily, hydroxyurea, in combination with didanosine, deserves reevaluation for the long-term management of HIV/AIDS worldwide, because of its excellent resistance profile, durability, and affordability.

Original languageEnglish (US)
Pages (from-to)263-272
Number of pages10
JournalAIDS Research and Human Retroviruses
Volume21
Issue number4
DOIs
StatePublished - Apr 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Virology

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    Lori, F., Pollard, R. B., Whitman, L., Bakare, N., Blick, G., Shalit, P., Foli, A., Peterson, D., Tennenberg, A., Schrader, S., Rashbaum, B., Farthing, C., Herman, D., Norris, D., Greiger, P., Frank, I., Groff, A., Lova, L., Asmuth, D., & Lisziewicz, J. (2005). Lowering the dose of hydroxyurea minimizes toxicity and maximizes anti-HIV potency. AIDS Research and Human Retroviruses, 21(4), 263-272. https://doi.org/10.1089/aid.2005.21.263