title: Residual HIV-1 replication may impact immune recovery in patients on first-line lopinavir/ritonavir monotherapy.
abstract: BACKGROUND
  Antiretroviral combination therapy raises issues of long-term adherence and toxicity. Initial treatment simplification based on single-drug therapy was investigated in the MONARK trial, which compared first-line lopinavir/ritonavir monotherapy (arm A) with first-line lopinavir/ritonavir + zidovudine/lamivudine tritherapy (arm B). The MONARK trial is registered as a randomized trial at clinical trials.gov under identifier NCT 00234923.
  
  
  METHODS
  Immune recovery was compared in patients with undetectable plasma virus (<50 copies/mL) after 60 weeks of treatment (arm A, n = 21; arm B, n = 13).
  
  
  RESULTS
  The week 60 CD4 T cell count and CD4 T cell subset distribution did not differ significantly between the treatment arms. Memory CD4 T cell responses to HIV and recall antigens were better with triple therapy than with monotherapy. The frequencies of activated CD8 T cells and anti-HIV CD8 T cell effector responses were similar in the two arms. However, the repertoire of CD8 T cell effector responses was broader and persistent residual viraemia more frequent (by ultrasensitive PCR) in the monotherapy arm.
  
  
  CONCLUSIONS
  While viral control can be achieved with first-line lopinavir/ritonavir monotherapy, the quality of immune recovery is inferior to that obtained with triple therapy, possibly owing to a higher level of residual viral replication. Thus, the benefits of first-line lopinavir/ritonavir monotherapy in terms of toxicity and adherence might be offset by an increased risk of residual viral replication, which may also fuel latent viral reservoirs.
authors.affiliation: INSERM U-1184, Université Paris-Sud, Le Kremlin-Bicêtre, France Department of Pediatrics, Nimes University Hospital, Nimes, France.
authors.forename: Tu-Anh
authors.initials: TA
authors.lastname: Tran
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, EA 7327 Paris, France APHP, UF de Thérapeutique en Immuno-Infectiologie, CHU Hotel Dieu, Paris, France.
authors.forename: Jade
authors.initials: J
authors.lastname: Ghosn
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, EA 7327 Paris, France APHP, Laboratoire de Virologie, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Avettand-Fenoël
authors.affiliation: INSERM U-1184, Université Paris-Sud, Le Kremlin-Bicêtre, France Laboratoire d'Immunologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
authors.forename: Houria
authors.initials: H
authors.lastname: Hendel-Chavez
authors.affiliation: INSERM U-1184, Université Paris-Sud, Le Kremlin-Bicêtre, France Laboratoire d'Immunologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
authors.forename: Marie-Ghislaine
authors.initials: MG
authors.lastname: de Goër de Herve
authors.affiliation: AbbVie France, Rungis, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cohen-Codar
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, EA 7327 Paris, France APHP, Laboratoire de Virologie, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.affiliation: INSERM U-1184, Université Paris-Sud, Le Kremlin-Bicêtre, France AP-HP, Department of Internal Medicine, Bicetre University Hospital, Le Kremlin-Bicetre, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
authors.affiliation: INSERM U-1184, Université Paris-Sud, Le Kremlin-Bicêtre, France Laboratoire d'Immunologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France yassine.taoufik@bct.aphp.fr.
authors.forename: Yassine
authors.initials: Y
authors.lastname: Taoufik
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003430:Cross-Sectional Studies; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D061466:Lopinavir / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D004338:Drug Combinations; C558899:lopinavir-ritonavir drug combination; D061466:Lopinavir; D019438:Ritonavir
keywords: HIV; antiviral; effector memory CD8 T cells