Impact of first-line protease inhibitors on predicted resistance to tipranavir in HIV-1-infected patients with virological failure.
BACKGROUND
Tipranavir (TPV) is a recently approved nonpeptidic protease inhibitor (PI) of HIV-1 and has been indicated for those infected with PIs-resistant HIV-1. However, in clinical practice, whether the HIV-1 from the patients with virological failure to the regimens containing first-line PIs remains susceptible to TPV/r may be questionable.


METHODS
To assess the resistance levels to TPV of HIV-1 from patients with treatment failure to first-line PIs, patients who experienced virological failure were tested for genotypic resistance of HIV-1 since August 2006 in National Taiwan University Hospital. Patients were enrolled for this analysis if their failed regimens contained > 12 weeks of atazanavir or lopinavir/ritonavir (defined as ATV group and LPV/r group, respectively), but were excluded if they experienced both or other PIs. The levels of genotypic resistance to TPV/r were determined by TPV mutation score.


RESULTS
Till May 2008, 21 subjects in ATV group and 20 subjects in LPV/r group were enrolled. The TPV mutation scores in subjects in LPV/r group were significantly higher than these in ATV group (median, 3 vs 1, P = 0.007). 95.2% subjects in ATV group and only 45% subjects in LPV/r group had an estimated maximal virological response to TPV/r (P < 0.001). The resistance levels to TPV/r correlated with the duration of exposure to first-line PIs, whether in ATV or LPV/r group.


CONCLUSIONS
Cross-resistance from first-line PIs may impede the effectiveness of TPV/r-containing salvage therapy. TPV/r should be used cautiously for patients with virological failure to LPV/r especially long duration of exposure.
Hsieh
Szu-Min
SM
Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China. hsmaids@hotmail.com
Chang
Sui-Yuan
SY
Hung
Chien-Ching
CC
Sheng
Wang-Huei
WH
Chen
Mao-Yuan
MY
Chang
Shan-Chwen
SC
D000328:Adult; D000069446:Atazanavir Sulfate; D004252:DNA Mutational Analysis; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use; D011753:Pyrones / Q000627:therapeutic use*; D012367:RNA, Viral / Q000235:genetics; D019438:Ritonavir / Q000627:therapeutic use; D013449:Sulfonamides; D017211:Treatment Failure; D055815:Young Adult
D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D011744:Pyrimidinones; D011753:Pyrones; D012367:RNA, Viral; D013449:Sulfonamides; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D019438:Ritonavir; C107201:tipranavir