title: Tipranavir/T20-based salvage regimens highly effective and durable against HIV-1 with evidence for genotypic predictability of response in clinical practice.
abstract: Escalating drug resistance in treatment-experienced HIV-1-infected patients has made management increasingly difficult. In clinical trials, tipranavir (TPV) has produced potent and durable responses in such patients, although experience in clinical cohorts is limited. A retrospective clinical case review was undertaken of triple-class experienced HIV-1-infected patients receiving optimized boosted TPV-containing regimens and T20 with up to 108 weeks follow-up. Antiretroviral therapy (ART) resistance profiles were characterized using International Aids Society (IAS)-USA scoring and 'TPV resistance score' (TPV-RS) at baseline and failure. Five of 12 patients had undetectable virus (<50 copies/mL) after median 84 weeks (range 60-108), and 1/12 < had 700 copies/mL after 40 weeks. Six of 12 patients failed after 36 (range 12-48) weeks and were more likely to have > or = 3 TPV-RS mutations than non-failures (P = 0.06). Presence of a major IAS-USA mutation at baseline was strongly associated with absence of a 1 log viral load drop at 24 weeks (P = 0.02). TPV-containing regimens showed impressive efficacy and tolerability in this heavily experienced cohort.
authors.affiliation: Barts and The London NHS Trust, London, UK.
authors.forename: R K
authors.initials: RK
authors.lastname: Gupta
authors.forename: Clive
authors.initials: C
authors.lastname: Loveday
authors.forename: U
authors.initials: U
authors.lastname: Kalidindi
authors.forename: M
authors.initials: M
authors.lastname: Lechelt
authors.forename: Celia
authors.initials: C
authors.lastname: Skinner
authors.forename: Chloe
authors.initials: C
authors.lastname: Orkin
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D000077560:Enfuvirtide; D005838:Genotype; D015700:HIV Envelope Protein gp41 / Q000627:therapeutic use*; D023581:HIV Fusion Inhibitors / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D010446:Peptide Fragments / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D011753:Pyrones / Q000627:therapeutic use*; D012189:Retrospective Studies; D016879:Salvage Therapy; D013449:Sulfonamides; D016896:Treatment Outcome