title: Activity, safety, and immunological effects of hydroxyurea added to didanosine in antiretroviral-naive and experienced HIV type 1-infected subjects: a randomized, placebo-controlled trial, ACTG 307.
abstract: We performed a 24-week, placebo-controlled, comparative trial of hydroxyurea (HU) monotherapy, didanosine(ddI) monotherapy, and the combination of ddI plus HU administered as 1000 mg qd or 1500 mg qd in antiretroviral-naive and experienced subjects with CD4+ lymphocyte counts of 200-700 cells/mm3. Enrollment included 134 subjects. HU enhanced the antiviral activity of ddI by 1.0 log10 copies/ml after 8 weeks of therapy, with sustained responses over 24 weeks. HU alone over 4 weeks had no effect. Lamivudine resistance had little impact on antiretroviral activity when examined across treatment arms. Increases in absolute CD4+ T cell counts, but not CD4+ T cell percentages, were less in subjects who received HU compared to ddI monotherapy, and lymphoproliferative responses to antigenic and mitogenic stimuli were not altered. Subjects who received HU 1500 mg were more likely to experience dose-limiting hematological toxicities compared to those who received 1000 mg, without any additional antiviral benefit. HU may continue to have a role as a component of HIV therapy.
authors.forename: Ian
authors.initials: I
authors.lastname: Frank
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Bosch
authors.forename: Susan
authors.initials: S
authors.lastname: Fiscus
authors.forename: Fred
authors.initials: F
authors.lastname: Valentine
authors.forename: Charles
authors.initials: C
authors.lastname: Flexner
authors.forename: Yoninah
authors.initials: Y
authors.lastname: Segal
authors.forename: Ping
authors.initials: P
authors.lastname: Ruan
authors.forename: Roy
authors.initials: R
authors.lastname: Gulick
authors.forename: Kenneth
authors.initials: K
authors.lastname: Wood
authors.forename: Scharla
authors.initials: S
authors.lastname: Estep
authors.forename: Lawrence
authors.initials: L
authors.lastname: Fox
authors.forename: Thomas
authors.initials: T
authors.lastname: Nevin
authors.forename: Michael
authors.initials: M
authors.lastname: Stevens
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D019384:Nucleic Acid Synthesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D019384:Nucleic Acid Synthesis Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D016049:Didanosine; D006918:Hydroxyurea