title: Efficacy of indinavir-ritonavir-based regimens in HIV-1-infected patients with prior protease inhibitor failures.
abstract: OBJECTIVE
  To assess responses to indinavir (IDV)-ritonavir (RTV)-based regimens among HIV-1 infected patients with prior failure of protease inhibitors, and to assess the effects of adherence to therapy and pre-existing genotypic and phenotypic resistance on this response.
  
  
  METHODS
  Twenty-eight patients initiating salvage regimens with IDV-RTV (800 mg and 200 mg twice daily, respectively) plus one or more reverse transcriptase inhibitor (RTI) were identified retrospectively. Genotypic and phenotypic susceptibilities to multiple antiretroviral agents were determined on viral samples collected at initiation of the salvage regimens, and adherence to therapy was determined through patient self-reporting. Response to therapy (viral RNA </= 400 copies/ml) was assessed at the end of and beyond 6 months of follow-up.
  
  
  RESULTS
  Based on responses measured in the first 6 months of follow-up, 16 responders and 12 non-responders were identified without differences in baseline demographic factors, laboratory parameters, extent of prior antiretroviral therapy, or characteristics of the RTI components of the new IDV-RTV-based regimens. Adequate adherence was associated with virologic responses (P = 0.005). There were trends for genotypic and phenotypic resistance to be associated with adequate adherence, and, surprisingly, phenotypic resistance to IDV was associated with virologic response rather than with therapeutic failure (P = 0.02). Beyond 6 months of follow-up (mean follow-up 69 weeks), adequate adherence was still associated with virologic response (P = 0.001), but genotypic or phenotypic resistance to IDV were not associated with therapeutic failure.
  
  
  CONCLUSIONS
  These results suggest that IDV-RTV-based regimens may be able to overcome IDV resistance. This underscores the importance of drug adherence, potency, and exposure in determining virologic responses to antiretroviral therapy.
authors.affiliation: Department of Pathology, University of Miami School of Medicine, Florida, USA.
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Campo
authors.forename: Jose N
authors.initials: JN
authors.lastname: Moreno
authors.forename: German
authors.initials: G
authors.lastname: Suarez
authors.forename: Nancimae
authors.initials: N
authors.lastname: Miller
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kolber
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Holder
authors.forename: Malathi
authors.initials: M
authors.lastname: Shivaprakash
authors.forename: Dana M
authors.initials: DM
authors.lastname: DeAngelis
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Wright
authors.forename: William A
authors.initials: WA
authors.lastname: Schleif
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Emini
authors.forename: Jon H
authors.initials: JH
authors.lastname: Condra
mesh_terms: D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use*; D008297:Male; D010349:Patient Compliance; D010641:Phenotype; D012189:Retrospective Studies; D019438:Ritonavir / Q000627:therapeutic use*; D016879:Salvage Therapy / Q000379:methods; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir; D016333:HIV Protease; D019438:Ritonavir