title: Long-term efficacy and safety of tipranavir boosted with ritonavir in HIV-1-infected patients failing multiple protease inhibitor regimens: 80-week data from a phase 2 study.
abstract: BACKGROUND
  BI 1182.2, an open-label, randomized, multicenter, phase 2 study, evaluated efficacy and tolerability of the protease inhibitor (PI) tipranavir (TPV; 500 mg twice daily or 1000 mg twice daily) administered with ritonavir (100 mg twice daily) in combination with 1 nucleoside reverse transcriptase inhibitor and 1 nonnucleoside reverse transcriptase inhibitor in multiple PI-experienced HIV-1-infected patients.
  
  
  METHODS
  Forty-one patients were evaluated in 2 arms: low-dose (19 patients) or high-dose (22 patients) ritonavir-boosted tipranavir (TPV/r). Primary endpoints were change from baseline in HIV-1 RNA concentrations at weeks 16, 24, 48, and 80 and percentage of patients with plasma HIV-1 RNA levels lower than the limit of quantitation. Safety was evaluated by adverse events (AEs), grade 3/4 abnormalities, and serious AEs.
  
  
  RESULTS
  Of all patients, 59% were still receiving TPV/r (14 in low-dose arm and 10 in high-dose arm) at week 80. Patients in both arms had a median >2.0-log10 reduction in plasma viral load. Intent-to-treat analysis demonstrated that a similar proportion of patients in the high-dose and low-dose groups achieved plasma HIV-1 RNA levels <50 copies/mL at week 80 (43% vs. 32%; P = 0.527). The most frequently observed AEs were diarrhea, headache, and nausea.
  
  
  CONCLUSIONS
  TPV/r combined with other active antiretroviral agents can provide a durable treatment response for highly treatment-experienced patients.
authors.affiliation: Aaron Diamond AIDS Research Center, Rockefeller University, 455 First Avenue, New York, NY 10016, USA. mmarkowitz@adarc.org
authors.forename: Martin
authors.initials: M
authors.lastname: Markowitz
authors.forename: Leonard N
authors.initials: LN
authors.lastname: Slater
authors.forename: Robert
authors.initials: R
authors.lastname: Schwartz
authors.forename: Powel H
authors.initials: PH
authors.lastname: Kazanjian
authors.forename: Bruce
authors.initials: B
authors.lastname: Hathaway
authors.forename: David
authors.initials: D
authors.lastname: Wheeler
authors.forename: Mitchell
authors.initials: M
authors.lastname: Goldman
authors.forename: Dietmar
authors.initials: D
authors.lastname: Neubacher
authors.forename: Douglas
authors.initials: D
authors.lastname: Mayers
authors.forename: Hernan
authors.initials: H
authors.lastname: Valdez
authors.forename: Scott
authors.initials: S
authors.lastname: McCallister
mesh_terms: D000328:Adult; D000368:Aged; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011753:Pyrones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D017320:HIV Protease Inhibitors; D011725:Pyridines; D011753:Pyrones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; D019438:Ritonavir; C107201:tipranavir