title: A cytostatic drug improves control of HIV-1 replication during structured treatment interruptions: a randomized study.
abstract: OBJECTIVE
  To study the effect of highly active antiretroviral therapy (HAART) with and without hydroxyurea (HU) on changes in plasma viral load (VL) set-point, and on HIV-1-specific responses, after five cycles of structured treatment interruptions (STI).
  
  
  METHODS
  A group of 20 patients taking HAART for chronic HIV infection with VL < 20 copies/ml were randomized to continue HAART or HAART plus HU for 24 weeks followed by five STI cycles. HU was also stopped in cycles 1-3 but continued in cycles 4 and 5. The number of individuals maintaining a VL set-point < 5000 copies/ml during the fifth interruption were determined.
  
  
  RESULTS
  VL remained < 5000 copies/ml in eight out of nine patients in the HU group and in four out of ten patients in the HAART group after a median 48 weeks of follow-up after the fifth interruption ( P=0.039). By STI cycle 5, there was a significant increase in the neutralizing activity (NA), in both magnitude and breadth of the total cytotoxic T lymphocyte (CTL) response and in lymphoproliferative response (LPR) from baseline. No significant differences were observed between HAART and HU groups in NA, CTL and LPR at any time-point. There were no differences in the NA titers at any time-point between responder and non-responder patients. There was a trend for higher CTL and LPR levels in responder patients (P= 0.10).
  
  
  CONCLUSIONS
  In this randomized, controlled study of STI with cycles of HAART or HAART plus HU, a lower peak VL rebound and a lower VL set-point was achieved in patients continuing HU while other drugs were discontinued. HU did not blunt anti-HIV-1-specific responses; however, control of VL did not correlate with anti-HIV-1-specific cellular immune responses.
authors.affiliation: Infectious Diseases Unit, Clinic Institute of Infectious Diseases and Immunology, Institut d'Investigacions Biomèdiques August Pi I Sunyer, Hospital Clínic, Faculty of Medicine, University of Barcelona, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: García
authors.forename: Montserrat
authors.initials: M
authors.lastname: Plana
authors.forename: Mireia
authors.initials: M
authors.lastname: Arnedo
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Ortiz
authors.forename: José M
authors.initials: JM
authors.lastname: Miró
authors.forename: Lucia
authors.initials: L
authors.lastname: Lopalco
authors.forename: Franco
authors.initials: F
authors.lastname: Lori
authors.forename: Tomás
authors.initials: T
authors.lastname: Pumarola
authors.forename: Teresa
authors.initials: T
authors.lastname: Gallart
authors.forename: José M
authors.initials: JM
authors.lastname: Gatell
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; 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 / Q000627:therapeutic use*; D008297:Male; D019384:Nucleic Acid Synthesis Inhibitors / Q000627:therapeutic use; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D019384:Nucleic Acid Synthesis Inhibitors; D006918:Hydroxyurea