title: Raltegravir as functional monotherapy leads to virological failure and drug resistance in highly treatment-experienced HIV-infected patients.
abstract: The objective of this study was to evaluate the development of resistance to raltegravir (RAL) in patients with viraemia between 40 and 400 copies/ml. All HIV-1-infected patients with multidrug-resistant virus, plasma HIV-1 RNA >1000 copies/ml and starting RAL were enrolled in this observational study and followed up until week 48. Sixty-seven patients with median plasma HIV-1 RNA at 4.3 log(10) copies/ml and CD4 at 177 cells/mm(3) were included. At week 24, 43 achieved full viral suppression (FVS; plasma HIV-1 RNA <40 copies/ml), 18 had incomplete viral suppression (IVS; plasma HIV-1 RNA 40-<or=400 copies/ml) and 6 experienced virological failure (VF; plasma HIV-1 RNA >400 copies/ml). At week 48, all the FVS were sustained, 16 of the IVS patients retained a plasma HIV-1 RNA <400 copies/ml and only 2 of the IVS at week 24 experienced VF. No RAL resistance was detected in the persistent low viraemia. In contrast, integrase mutation was detected in 6 of the patients with VF. A genotypic sensitivity score equal to 0 was associated with plasma HIV-1 RNA >40 copies/ml at week 24 (OR 20.9, 95% CI 2.0-215.1) and with RAL resistance (OR 14.2, 95% CI 2.1-94.7). This study confirmed the high efficacy of a RAL-containing regimen under routine clinical conditions in infections caused by multidrug-resistant virus. If persistent low viraemia is observed over more than 48 weeks without the emergence of resistance, RAL should never be given as functional monotherapy, as it is associated with a maximal risk of VF and the emergence of RAL resistance.
authors.affiliation: Service des Maladies Infectieuses et Tropicales, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Caby
authors.forename: Nadia
authors.initials: N
authors.lastname: Valin
authors.forename: Anne Genevieve
authors.initials: AG
authors.lastname: Marcelin
authors.forename: Luminata
authors.initials: L
authors.lastname: Schneider
authors.forename: Régis
authors.initials: R
authors.lastname: Andrade
authors.forename: Marguerite
authors.initials: M
authors.lastname: Guiguet
authors.forename: Roland
authors.initials: R
authors.lastname: Tubiana
authors.forename: Ana
authors.initials: A
authors.lastname: Canestri
authors.forename: Marc Antoine
authors.initials: MA
authors.lastname: Valantin
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Jérome
authors.initials: J
authors.lastname: Pacanowski
authors.forename: Laurence
authors.initials: L
authors.lastname: Morand-Joubert
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.forename: Pierre Marie
authors.initials: PM
authors.lastname: Girard
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D011760:Pyrrolidinones / Q000494:pharmacology / 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