title: Alternation of antiretroviral drug regimens for HIV infection. Efficacy, safety and tolerability at week 96 of the Swatch Study.
abstract: BACKGROUND
  Alternation of antiretroviral drug regimens has been proposed as a novel treatment strategy for HIV infection. However, some concerns persist regarding antiviral efficacy, adherence, toxicity and resistance evolution in the long term.
  
  
  METHODS
  A total of 161 antiretroviral-naive HIV-1-infected patients were randomized to receive stavudine/didanosine/efavirenz (group A) or zidovudine/lamivudine/ nelfinavir (group B) or to alternate between the two regimens every 3 months starting with regimen A (group C). Antiviral efficacy, adherence, safety and tolerability were analysed every 12 weeks.
  
  
  RESULTS
  After 96 weeks, time to virological failure was significantly delayed in the alternating regimen compared with the standards of care regimens. Virological suppression was seen in 46%, 48% and 58% of patients in groups A, B and C, respectively, in the intention-to-treat analysis and in 75%, 76% and 97% in the on-treatment analysis (A vs C: P=0.014; B vs C: P=0.016; A vs B: P=0.849). At the end of the study, 94% of patients in group A and 92% in groups B and C reported an adherence greater than 95%. Alternating therapy was associated with a similar impact on CD4+ counts in comparison with the standards of care regimens, as well as a lower mitochondrial DNA/nuclear DNA (mtDNA/nDNA) ratio decrease in the mitochondrial substudy performed on 37 patients. The frequency and intensity of adverse events in the alternating group decreased during subsequent cycles.
  
  
  CONCLUSIONS
  Our results favour the hypothesis that proactive therapy switching may delay the accumulation of resistance mutations. Moreover, the alternating regimen was well tolerated and adherence remained comparably high in all treatment groups. The lower mtDNA/nDNA ratio decrease observed in this group may imply a lower impact on mitochondrial toxicity than in standard regimens.
authors.affiliation: Department of Internal Medicine, Lluita contra la SIDA and IrsiCaixa Foundations, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain. enegredo@h0600.hugtip.scs.es
authors.forename: Eugenia
authors.initials: E
authors.lastname: Negredo
authors.forename: Roger
authors.initials: R
authors.lastname: Paredes
authors.forename: Joaquim
authors.initials: J
authors.lastname: Peraire
authors.forename: Enric
authors.initials: E
authors.lastname: Pedrol
authors.forename: Helene
authors.initials: H
authors.lastname: Côté
authors.forename: Silvia
authors.initials: S
authors.lastname: Gel
authors.forename: Carmina R
authors.initials: CR
authors.lastname: Fumoz
authors.forename: Lidia
authors.initials: L
authors.lastname: Ruiz
authors.forename: Vicente
authors.initials: V
authors.lastname: Abril
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rodriguez de Castro
authors.forename: Claudia
authors.initials: C
authors.lastname: Ochoa
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
authors.forename: Julio
authors.initials: J
authors.lastname: Montaner
authors.forename: Celestino
authors.initials: C
authors.lastname: Rey-Joly
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D010349:Patient Compliance; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors