title: Short communication: activity of etravirine on different HIV type 1 subtypes: in vitro susceptibility in treatment-naive patients and week 48 pooled DUET study data.
abstract: Etravirine (ETR) has previously shown potent in vitro activity against different primary HIV-1 isolates and demonstrated durable efficacy in treatment-experienced, HIV-1-infected patients in the Phase III DUET studies. The antiviral activity and efficacy of ETR against HIV-1 subtypes B and non-B were further investigated. The effect of HIV-1 subtype on ETR fold change in EC(50) value (FC) was analyzed in HIV-1 recombinant clinical isolates from 673 treatment-naive patients enrolled in other Tibotec studies. Subgroup analyses from the DUET studies of the effect of HIV-1 subtype on the proportion of patients with viral load (VL) <50 HIV-1 RNA copies/ml were also conducted using pooled week 48 data. Genotype/subtype and phenotype determinations were performed using the vircoTYPE HIV-1 and Antivirogram assays, respectively. In vitro results from treatment-naive patients indicated comparable median ETR FC in virus isolates from patients infected with subtype B or non-B (1.1 vs. 1.2, respectively). HIV-1 subtype data were available for 594 and 595 patients in the ETR and placebo groups of the DUET studies, respectively; 94% of patients harbored subtype B. Baseline characteristics were similar across the different subtypes, with the exception of a higher number of sensitive NRTIs used in patients with subtype non-B. At week 48, virological responses in the ETR group were higher in patients with subtype non-B versus B (73% vs. 60%, respectively). ETR was equally effective in suppressing viral replication in patients infected with HIV-1 subtype B or various HIV-1 non-B subtypes.
authors.affiliation: Tibotec BVBA, Mechelen, Belgium. jvingerh@its.jnj.com
authors.forename: Johan
authors.initials: J
authors.lastname: Vingerhoets
authors.forename: Hilde
authors.initials: H
authors.lastname: Azijn
authors.forename: Lotke
authors.initials: L
authors.lastname: Tambuyzer
authors.forename: Inge
authors.initials: I
authors.lastname: Dierynck
authors.forename: Sandra
authors.initials: S
authors.lastname: De Meyer
authors.forename: Laurence
authors.initials: L
authors.lastname: Rimsky
authors.forename: Steven
authors.initials: S
authors.lastname: Nijs
authors.forename: Goedele
authors.initials: G
authors.lastname: De Smedt
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: de Béthune
authors.forename: Gaston
authors.initials: G
authors.lastname: Picchio
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D009570:Nitriles; D010641:Phenotype; D011724:Pyridazines / Q000494:pharmacology* / Q000627:therapeutic use; D011743:Pyrimidines; D012367:RNA, Viral / Q000235:genetics; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D012367:RNA, Viral; C451734:etravirine