title: Combination therapy with indinavir, ritonavir, and delavirdine and nucleoside reverse transcriptase inhibitors in patients with HIV/AIDS who have failed multiple antiretroviral combinations.
abstract: OBJECTIVE
  Ritonavir (RTV) and delavirdine (DLV) are inhibitors of cytochrome P450 (CYP) 3A4, the specific CYP that metabolizes indinavir (IDV). We hypothesized that patients who have failed multiple therapies containing protease inhibitors would still respond to IDV if high plasma concentrations were achieved. We retrospectively examined the antiviral efficacy of the combination of RTV, DLV, and IDV in heavily antiretroviral-experienced patients.
  
  
  METHODS
  A chart review of patients treated with IDV/RTV/DLV and two nucleoside reverse transcriptase inhibitor (NRTI) drugs was performed. Only patients who failed at least three highly active antiretroviral therapy (HAART) regimens and remained on IDV/RTV/DLV therapy for at least 2 months were included. Plasma concentrations for IDV and RTV were obtained if patients were still on therapy.
  
  
  RESULTS
  Ten participants were identified who qualified for this study. The median plasma HIV RNA prior to initiating IDV/RTV/DLV was 359,300 copies/mL. Nine of the 10 patients had failed nonnucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens in the past. Eight out of 10 patients had at reduction in HIV RNA. Four of eight patients maintained the 1 log(10) reduction in HIV RNA past 6 months. Mean CD4 cell count increased from 142+/-99 to 273+/-126 cells/mm(3). Genotypic data available on six patients showed multiple protease gene mutations. Plasma concentration of IDV in three patients (two troughs and one 7 hours postdose) were >1,000 ng/mL.
  
  
  CONCLUSIONS
  Our data suggests that in heavily antiretroviral drug-treated patients, partial antiretroviral response to RTV/IDV/DLV can still be achieved. The use of IDV/RTV/DLV and two NRTIs as salvage therapy has merit in patients who have no viable treatment options. A prospective trial utilizing this drug combination is warranted.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
authors.forename: M
authors.initials: M
authors.lastname: Grodesky
authors.forename: E P
authors.initials: EP
authors.lastname: Acosta
authors.forename: N
authors.initials: N
authors.lastname: Fujita
authors.forename: S
authors.initials: S
authors.lastname: Mason
authors.forename: J G
authors.initials: JG
authors.lastname: Gerber
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D020008:Delavirdine / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D016333:HIV Protease / Q000235:genetics; D015497:HIV-1 / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D019469:Indinavir / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019438:Ritonavir / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016879:Salvage Therapy; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019469:Indinavir; D020008:Delavirdine; D016333:HIV Protease; D019438:Ritonavir