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.
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.
Markowitz
Martin
M
Aaron Diamond AIDS Research Center, Rockefeller University, 455 First Avenue, New York, NY 10016, USA. mmarkowitz@adarc.org
Slater
Leonard N
LN
Schwartz
Robert
R
Kazanjian
Powel H
PH
Hathaway
Bruce
B
Wheeler
David
D
Goldman
Mitchell
M
Neubacher
Dietmar
D
Mayers
Douglas
D
Valdez
Hernan
H
McCallister
Scott
S
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
D017320:HIV Protease Inhibitors; D011725:Pyridines; D011753:Pyrones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; D019438:Ritonavir; C107201:tipranavir