title: Emerging HIV-1 resistance to tipranavir and darunavir in patients with virological failure to first-generation protease inhibitors in Taiwan.
abstract: Ritonavir-boosted tipranavir (TPV/r) and darunavir (DRV/r) have been approved in patients with virological resistance to multiple protease inhibitors (PIs). Whether the HIV-1 from these patients with virological failure to first-generation PIs remains susceptible to TPV/r or DRV/r is questionable. The susceptibilities of HIV-1 isolates to second-generation PIs in patients who experienced virological failure in three time periods were analysed: 9-2006 to 4-2007 (period 1), 5-2007 to 12-2007 (period 2) and 1-2008 to 8-2008 (period 3). A total of 53 subjects were enrolled, and 51 subject isolates (96.2%) were resistant to ≥1 PIs. The mutation scores for TPV and DRV, and the percentage of isolates with resistance to TPV or DRV, increased significantly from period 1 to period 3. Our data revealed a significant increase in the levels of genotypic resistance to TPV and DRV over the past two years in patients with virological failure to first-generation PIs.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan UniversityCollege of Medicine, Taipei, Taiwan. hsmaids@hotmail.com
authors.forename: S-M
authors.initials: SM
authors.lastname: Hsieh
authors.forename: S-Y
authors.initials: SY
authors.lastname: Chang
authors.forename: C-C
authors.initials: CC
authors.lastname: Hung
authors.forename: W-H
authors.initials: WH
authors.lastname: Sheng
authors.forename: M-Y
authors.initials: MY
authors.lastname: Chen
authors.forename: S-C
authors.initials: SC
authors.lastname: Chang
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D000069454:Darunavir; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011725:Pyridines / Q000008:administration & dosage* / Q000494:pharmacology; D011753:Pyrones / Q000008:administration & dosage* / Q000494:pharmacology; D013449:Sulfonamides / Q000008:administration & dosage* / Q000494:pharmacology; D013624:Taiwan; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011725:Pyridines; D011753:Pyrones; D013449:Sulfonamides; D016333:HIV Protease; D000069454:Darunavir; C107201:tipranavir