title: Withdrawing inactive NRTIs in HIV-1 subjects with suppressed viraemia: a randomized trial.
abstract: BACKGROUND
  Extensively pretreated subjects with virological failure (VF) may receive salvage regimens containing NRTIs with only residual or no activity. Once virological suppression is achieved, their contribution remains elusive.
  
  
  METHODS
  This was a multicentre, randomized, prospective study. Subjects with at least one prior VF, HIV-1 RNA <50 copies/mL for ≥6 months and receiving a regimen with at least two active drugs (one of them a boosted PI) were randomized 1:1 to stop (experimental arm) or maintain (control arm) NRTIs. EudraCT: 2012-000198-21.
  
  
  RESULTS
  Ninety subjects were randomized (experimental, n = 45; and control, n = 45). The mean age was 50 years, 80% were male, the mean CD4+ cell count was 542 cells/mm(3) and the median number of prior VFs was 3. Seventy-four subjects (82%) harboured the mutation M184V/I and the median number of thymidine-associated mutations was 3 (IQR: 0-4). In the experimental arm, thirty-two (71%) subjects removed one NRTI and 13 (29%) subjects removed two. Twenty-two of 45 (49%) discontinued tenofovir disoproxil fumarate. Forty-one of 45 (91.1%, experimental arm) and 44 of 45 (97.8%, control arm) had HIV-1 RNA <50 copies/mL at 48 weeks (difference: -6.7%; 95% CI: -17.4, 4.1). In a post-hoc analysis allowing NRTI reintroduction, efficacy rates were 95.6% and 97.8%, respectively (difference: -2.2%; 95% CI: -7.2, 2.7). Rates of discontinuation at 48 weeks were 2% in both arms. One subject developed a late VF with resistance selection.
  
  
  CONCLUSIONS
  In patients receiving a successful multidrug salvage regimen with at least two active drugs (one a boosted PI), the withdrawal of inactive NRTIs was safe, rates of VF were low and drug resistance was uncommon at 48 weeks in this small study. This strategy could potentially prevent long-term toxicities, reduce the number of drugs and reduce costs if non-inferiority was met in a fully powered trial.
authors.affiliation: HIV Unit and 'Lluita contra la SIDA' Foundation, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain Universitat Autònoma de Barcelona, Barcelona, Spain jmllibre@flsida.org.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Llibre
authors.affiliation: Internal Medicine Department, Complejo Hospitalario Universitario de Ferrol, A Coruña, Spain.
authors.forename: Hortensia
authors.initials: H
authors.lastname: Alvarez
authors.affiliation: Internal Medicine Department, Hospital Clínico Universitario, Santiago de Compostela, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Antela
authors.affiliation: HIV Unit and 'Lluita contra la SIDA' Foundation, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
authors.forename: Jessica
authors.initials: J
authors.lastname: Toro
authors.affiliation: Internal Medicine Department, Hospital Son Llàtzer, Mallorca, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Payeras
authors.affiliation: Infectious Diseases, Hospital Ramón y Cajal, IRYCIS, Madrid, Spain.
authors.forename: M Jesús
authors.initials: MJ
authors.lastname: Pérez-Elías
authors.affiliation: HIV Unit, Infectious Diseases Department, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Arkaitz
authors.initials: A
authors.lastname: Imaz
authors.affiliation: Infectious Diseases, Hospital Universitario de Elche, Elche, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Masià
authors.affiliation: HIV Unit and 'Lluita contra la SIDA' Foundation, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain Statistics and Operations Research Department, Universitat Politècnica de Catalunya-Barcelona Tech, Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Pérez-Alvarez
authors.affiliation: Infectious Diseases, Hospital Universitari Vall d'Hebró, Barcelona, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Burgos
authors.affiliation: HIV Unit and 'Lluita contra la SIDA' Foundation, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain Universitat de Vic (UVIC) - Universitat Central de Catalunya, Vic, Spain.
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome; D019562:Viral Load; D028761:Withholding Treatment
chemical_list: D019380:Anti-HIV Agents