title: Effects of treatment intensification with hydroxyurea in HIV-infected patients with virologic suppression.
abstract: BACKGROUND
  Virologic rebound can result from suboptimal antiviral potency in combination antiretroviral therapy.
  
  
  METHODS
  Multicenter, partially blinded, prospective, randomized study of 202 HIV-infected subjects to determine whether therapy intensification improves long-term rates of virologic suppression.
  
  
  METHODS
  Subjects had plasma HIV RNA < 200 copies/ml, CD4 cell count of > 200 x 10(6) cells/l, and treatment with indinavir (IDV) + zidovudine (ZDV) + lamivudine (3TC) for at least 6 months before randomization to stay on this regimen or to receive IDV + didanosine (ddI) + stavudine (d4T) plus or minus hydroxyurea (HU) (600 mg twice daily). Treatment failure was defined as either confirmed rebound of HIV RNA level to > 200 copies/ml or a drug toxicity necessitating treatment discontinuation.
  
  
  RESULTS
  Treatment failure occurred more frequently in subjects randomized to the HU-containing arm (32.4%), than in those taking IDV + ddI + d4T (17.6%) or IDV + ZDV + 3TC (7.6%). The time to treatment failure was shorter for the HU-containing arm compared with the IDV + ZDV + 3TC (P < 0.0001) or IDV + ddI + d4T arms (P = 0.032). Dose-limiting toxicities rather than virologic rebound accounted for the differences between treatment failure among the study arms. Pancreatitis led to treatment discontinuation in 4% of subjects in treatment arms containing ddI + d4T. Three subjects with pancreatitis died, all randomized to the HU-containing arm.
  
  
  CONCLUSIONS
  Switching to IDV + ddI + d4T + HU in patients treated with IDV + ZDV + 3TC was associated with a worse outcome, principally because of drug toxicity.
authors.affiliation: University of California at San Diego and the San Diego Veterans Affairs Healthcare System, San Diego, California 92103, USA.
authors.forename: D V
authors.initials: DV
authors.lastname: Havlir
authors.forename: P B
authors.initials: PB
authors.lastname: Gilbert
authors.forename: K
authors.initials: K
authors.lastname: Bennett
authors.forename: A C
authors.initials: AC
authors.lastname: Collier
authors.forename: M S
authors.initials: MS
authors.lastname: Hirsch
authors.forename: P
authors.initials: P
authors.lastname: Tebas
authors.forename: E M
authors.initials: EM
authors.lastname: Adams
authors.forename: L J
authors.initials: LJ
authors.lastname: Wheat
authors.forename: D
authors.initials: D
authors.lastname: Goodwin
authors.forename: S
authors.initials: S
authors.lastname: Schnittman
authors.forename: M K
authors.initials: MK
authors.lastname: Holohan
authors.forename: D D
authors.initials: DD
authors.lastname: Richman
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use / Q000633:toxicity*; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use / Q000633:toxicity*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use / Q000633:toxicity*; D019469:Indinavir / Q000627:therapeutic use / Q000633:toxicity; D019259:Lamivudine / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D019384:Nucleic Acid Synthesis Inhibitors / Q000627:therapeutic use / Q000633:toxicity*; D010195:Pancreatitis / Q000139:chemically induced / Q000401:mortality; D011446:Prospective Studies; D016019:Survival Analysis; D017211:Treatment Failure; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir; D006918:Hydroxyurea