PMID- 17263650
OWN - NLM
STAT- MEDLINE
DCOM- 20070419
LR  - 20201209
IS  - 0889-2229 (Print)
IS  - 0889-2229 (Linking)
VI  - 23
IP  - 2
DP  - 2007 Feb
TI  - Efficacy and safety of three doses of tipranavir boosted with ritonavir in 
      treatment-experienced HIV type-1 infected patients.
PG  - 216-23
AB  - The efficacy, safety, and pharmacokinetics of three doses of tipranavir/ritonavir 
      (TPV/r) in highly treatment-experienced human immunodeficiency virus 
      (HIV)-1-infected patients with protease inhibitor (PI)-resistant isolates were 
      evaluated. A 24-week multicenter, double-blind, randomized, dose-finding trial 
      was conducted. All patients were three-drug class experienced and had taken at 
      least two PI-based regimens. All had at least one primary PI mutation and had 
      plasma HIV-RNA > 1000 copies/ml. Patients remained on their background non-PI 
      antiretroviral medications for the first 14 days. After this 14-day period of 
      functional TPV/r monotherapy, the background antiretroviral medications were 
      optimized based on treatment history and the screening genotype. A total of 216 
      patients were randomized. All groups [TPV/r 500 mg/100 mg (n = 73), 500 mg/200 mg 
      (n = 72), and 750 mg/200 mg (n = 71) twice daily] achieved an approximate 1 log10 
      reduction in the median HIV-RNA at week 2. A significant reduction was sustained 
      through 24 weeks in the TPV/r 500 mg/200 mg and 750 mg/200 mg groups. The 500 
      mg/200 mg dose achieved optimal median TPV trough concentrations and lower 
      interpatient variability. The most frequently reported adverse events (AEs) were 
      diarrhea, nausea, vomiting, fatigue, and headache. The TPV/r 750 mg/200 mg group 
      had the highest rate of grade 3 or 4 laboratory abnormalities and study 
      discontinuations due to AEs. All doses of TPV/r tested in this study were 
      associated with HIV-1 viral load reductions through 24 weeks. The 500 mg/200 mg 
      dose achieved the best efficacy, safety, and pharmacokinetic profile in this 
      highly treatment-experienced population and was selected for the pivotal phase 3 
      studies.
FAU - Gathe, Joseph C Jr
AU  - Gathe JC Jr
AD  - Therapeutic Concepts, 4900 Fannin Street, Houston, TX 77004, USA. 
      drgathe@josephgathe.com
FAU - Pierone, Gerald
AU  - Pierone G
FAU - Piliero, Peter
AU  - Piliero P
FAU - Arasteh, Keikawus
AU  - Arasteh K
FAU - Rubio, Rafael
AU  - Rubio R
FAU - Lalonde, Richard G
AU  - Lalonde RG
FAU - Cooper, David
AU  - Cooper D
FAU - Lazzarin, Adriano
AU  - Lazzarin A
FAU - Kohlbrenner, Veronika M
AU  - Kohlbrenner VM
FAU - Dohnanyi, Catherine
AU  - Dohnanyi C
FAU - Sabo, John
AU  - Sabo J
FAU - Mayers, Douglas
AU  - Mayers D
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - AIDS Res Hum Retroviruses
JT  - AIDS research and human retroviruses
JID - 8709376
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Pyridines)
RN  - 0 (Pyrones)
RN  - 0 (Sulfonamides)
RN  - O3J8G9O825 (Ritonavir)
RN  - ZZT404XD09 (tipranavir)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anti-HIV Agents/*administration & dosage/adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Drug Resistance, Multiple, Viral/*drug effects
MH  - Drug Therapy, Combination
MH  - Female
MH  - HIV Infections/*drug therapy
MH  - HIV-1/*drug effects
MH  - Humans
MH  - Male
MH  - Pyridines/*administration & dosage/adverse effects
MH  - Pyrones/*administration & dosage/adverse effects
MH  - Ritonavir/*administration & dosage/adverse effects
MH  - Sulfonamides
MH  - Treatment Outcome
EDAT- 2007/02/01 09:00
MHDA- 2007/04/20 09:00
CRDT- 2007/02/01 09:00
PHST- 2007/02/01 09:00 [pubmed]
PHST- 2007/04/20 09:00 [medline]
PHST- 2007/02/01 09:00 [entrez]
AID - 10.1089/aid.2006.0178 [doi]
PST - ppublish
SO  - AIDS Res Hum Retroviruses. 2007 Feb;23(2):216-23. doi: 10.1089/aid.2006.0178.