title: A cohort study of treatment-experienced HIV-1-infected patients treated with raltegravir: factors associated with virological response and mutations selected at failure.
abstract: This study aimed to identify factors associated with virological response (VR) to raltegravir (RAL)-containing regimens in 468 treatment-experienced but integrase inhibitor-naive HIV-1 patients receiving a RAL-containing regimen. VR was defined at Month 6 (M6) as HIV-1 RNA viral load (VL) <50 copies/mL. The impacts on VR of baseline integrase mutations, VL, CD4 count, genotypic sensitivity score for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors, and the number of new antiretrovirals used for the first time associated with RAL were investigated. For patients with VL >50 copies/mL at M6, integrase mutations selected were characterised. Median baseline VL was 4.2 log(10)copies/mL (IQR 3.3-4.9 log(10) copies/mL) and CD4 count was 219 cells/mm(3) (IQR 96-368 cells/mm(3)). At M6, 71% of patients were responders. In multivariate analysis, baseline VL and CD4 count and ≥ 2 new antiretrovirals among darunavir, etravirine, maraviroc and enfuvirtide were associated with VR to RAL. Neither HIV-1 subtype nor baseline integrase polymorphisms were associated with VR to RAL. Among 63 failing patients at M6, selection of ≥ 1 change in the integrase gene was observed in 49 (77.8%), and 27/63 (42.9%) were considered as RAL-associated resistance mutations. Factors independently associated with the occurrence of ≥ 1 RAL-associated resistance mutation were VL at failure >3 log(10) and having no new drugs associated with RAL. RAL showed great potency in treatment-experienced patients. The number of new drugs associated with RAL was an important factor associated with VR. HIV-1 subtype and baseline integrase polymorphisms do not influence the RAL VR.
authors.affiliation: Laboratoire de Virologie, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, UPMC Univ. Paris 06, INSERM U943, Paris, France. anne-genevieve.marcelin@psl.aphp.fr
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.forename: Constance
authors.initials: C
authors.lastname: Delaugerre
authors.forename: Céline
authors.initials: C
authors.lastname: Beaudoux
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
authors.forename: Laurence
authors.initials: L
authors.lastname: Morand-Joubert
authors.forename: Corinne
authors.initials: C
authors.lastname: Amiel
authors.forename: Veronique
authors.initials: V
authors.lastname: Schneider
authors.forename: Virginie
authors.initials: V
authors.lastname: Ferre
authors.forename: Jacques
authors.initials: J
authors.lastname: Izopet
authors.forename: Ali
authors.initials: A
authors.lastname: Si-Mohamed
authors.forename: Anne
authors.initials: A
authors.lastname: Maillard
authors.forename: Cécile
authors.initials: C
authors.lastname: Henquell
authors.forename: Delphine
authors.initials: D
authors.lastname: Desbois
authors.forename: Mouna
authors.initials: M
authors.lastname: Lazrek
authors.forename: Anne
authors.initials: A
authors.lastname: Signori-Schmuck
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rogez
authors.forename: Sabine
authors.initials: S
authors.lastname: Yerly
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Trabaud
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Plantier
authors.forename: Slim
authors.initials: S
authors.lastname: Fourati
authors.forename: Allal
authors.initials: A
authors.lastname: Houssaini
authors.forename: Bernard
authors.initials: B
authors.lastname: Masquelier
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.forename: Philippe
authors.initials: P
authors.lastname: Flandre
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D011760:Pyrrolidinones / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium