title: Determinants of virologic and immunologic outcomes in chronically HIV-infected subjects undergoing repeated treatment interruptions: the Istituto Superiore di Sanita-Pulsed Antiretroviral Therapy (ISS-PART) study.
abstract: BACKGROUND
  Factors influencing the outcome of structured treatment interruptions (STIs) in HIV chronic infection are not fully elucidated.
  
  
  METHODS
  In ISS-PART, 273 subjects were randomly assigned to arm A (137 assigned to continuous highly active antiretroviral therapy [HAART]) and arm B (136 assigned to 5 STIs of 1, 1, 2, 2, and 3 months' duration, each followed by 3 months of therapy). Main outcome measures were the proportion of subjects with a CD4 count >500 cells/mm3, the rate of virologic failure, and the emergence of resistance at 24 months.
  
  
  RESULTS
  The proportion of subjects with a CD4 count >500 cells/mm3 was higher in arm A than in arm B (86.5% vs. 69.1%; P = 0.0075). Pre-HAART CD4 cell count and male gender were independent predictors of a CD4 count >500 cells/mm3 in arm B. The overall risk of virologic failure was not increased in arm B; however, it was higher in the 38 subjects who had resistance mutations in the rebounding virus. Archived mutations at baseline and the use of a regimen that included an unboosted protease inhibitor (PI), compared with nonnucleoside reverse transcriptase inhibitor-based HAART, independently predicted the emergence of plasma mutations during STI (P = 0.002 for DNA mutations and P = 0.048 for PI-based HAART).
  
  
  CONCLUSIONS
  Our results suggest that patients with preexisting mutations and treated with unboosted PI-based HAART should not be enrolled in studies of time-fixed treatment interruptions, being at higher risk of developing plasma mutations during STI and virologic failure at therapy reinstitution.
authors.affiliation: Department of Drug Research and Evaluation, Instituto Superiore di Sanità, Rome, Italy. l.palmisano@iss.it
authors.forename: Lucia
authors.initials: L
authors.lastname: Palmisano
authors.forename: Marina
authors.initials: M
authors.lastname: Giuliano
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bucciardini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Fragola
authors.forename: Mauro
authors.initials: M
authors.lastname: Andreotti
authors.forename: Clementina
authors.initials: C
authors.lastname: Galluzzo
authors.forename: Maria F
authors.initials: MF
authors.lastname: Pirillo
authors.forename: Liliana E
authors.initials: LE
authors.lastname: Weimer
authors.forename: Romano
authors.initials: R
authors.lastname: Arcieri
authors.forename: Elena A P
authors.initials: EA
authors.lastname: Germinario
authors.forename: Roberta
authors.initials: R
authors.lastname: Amici
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Mancini
authors.forename: Antonella d'Arminio
authors.initials: Ad
authors.lastname: Monforte
authors.forename: Francesco
authors.initials: F
authors.lastname: Castelli
authors.forename: Pietro
authors.initials: P
authors.lastname: Caramello
authors.forename: Stefano
authors.initials: S
authors.lastname: Vella
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral