title: Immunity, inflammation and reservoir in patients at an early stage of HIV infection on intermittent ART (ANRS 141 TIPI Trial).
abstract: OBJECTIVE
  The objective of this study was to assess clinical and biological changes during intermittent ART (I-ART) started early, with significant time spent on versus off ART, which has never before been studied in ART-naive patients with high nadir and current CD4 cell count.
  
  
  METHODS
  ART-naive HIV-1-infected patients with baseline CD4 ≥ 500/mm(3) and nadir CD4 ≥ 400/mm(3) received 2 years of I-ART (6 month periods on once-daily boosted-PI-based ART, alternating with 6 month periods without ART) in a 2 year, Phase II, non-comparative multicentre trial. The trial is registered with ClinicalTrials.gov, number NCT 00820118.
  
  
  RESULTS
  The CD4 cell count remained ≥ 500/mm(3) at 2 years in all 44 patients included in the study. The mean 2 year count was higher than the mean count at baseline in 24 patients overall (55%; 95% CI 40%-69%) and in 20 (65%; 95% CI 48%-81%) of the 31 patients who fully adhered to the trial strategy. All but three of these latter patients had HIV-1 RNA concentrations below 50 copies/mL after each 6 month 'on' period. Only one strategy-related genotypic mutation (M184I) was detected. The HIV-1 DNA median load fluctuated, but it did not differ between month 0 and month 24 (2.8 versus 2.6 log10 copies/10(6) leucocytes, P = 0.29). Biomarkers of inflammation and endothelial activation remained stable between month 0 and month 24. Naive CD4, CD8+CCR5+ and CD8+CD38+ T cell numbers tended to decline. One patient developed Burkitt's lymphoma and 12 patients reported sexually transmitted infections.
  
  
  CONCLUSIONS
  In patients with high nadir and current CD4 cell counts, 2 year I-ART maintained the CD4 cell count above 500/mm(3), with no increase in the viral reservoir. Immune activation seems related to HIV replication, while inflammation seems to evolve independently and require specific attention.
authors.affiliation: Centre Hospitalier Universitaire Dijon, and Unité Mixte de Recherche 1347, Université de Bourgogne, Dijon, France lionel.piroth@chu-dijon.fr.
authors.forename: Lionel
authors.initials: L
authors.lastname: Piroth
authors.affiliation: University of Bordeaux, Institut de Santé Publique, d'Epidémiologie et de Développement, Centre INSERM U897- Epidemiologie-Biostatistique, F-33000 Bordeaux, France Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement, Centre INSERM U897- Epidemiologie-Biostatistique, F-33000 Bordeaux, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Moinot
authors.affiliation: Hôpital Bichat-Claude Bernard, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Yeni
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP) Hôpital Necker-Enfants Malades, Université Paris Descartes, Sorbonne Paris Cité EA7327, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Avettand-Fénoel
authors.affiliation: Centre Hospitalier Universitaire de Montpellier, Hôpital Gui de Chauliac, Université de Montpellier, UMI233 Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Reynes
authors.affiliation: Hôpital Saint-Antoine, Paris, France.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
authors.affiliation: Hôpital Purpan, Toulouse, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Marchou
authors.affiliation: University of Bordeaux, Institut de Santé Publique, d'Epidémiologie et de Développement, Centre INSERM U897- Epidemiologie-Biostatistique, F-33000 Bordeaux, France Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement, Centre INSERM U897- Epidemiologie-Biostatistique, F-33000 Bordeaux, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Georget
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP) Hôpital Necker-Enfants Malades, Université Paris Descartes, Sorbonne Paris Cité EA7327, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.affiliation: Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
authors.affiliation: Unité Mixte de Recherche U866, Université de Bourgogne, and Department of Biochemistry, Centre Hospitalier Universitaire, Dijon F-21000, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Duvillard
authors.affiliation: University of Bordeaux, Institut de Santé Publique, d'Epidémiologie et de Développement, Centre INSERM U897- Epidemiologie-Biostatistique, F-33000 Bordeaux, France Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement, Centre INSERM U897- Epidemiologie-Biostatistique, F-33000 Bordeaux, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chêne
authors.affiliation: University of Bordeaux, Institut de Santé Publique, d'Epidémiologie et de Développement, Centre INSERM U897- Epidemiologie-Biostatistique, F-33000 Bordeaux, France Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement, Centre INSERM U897- Epidemiologie-Biostatistique, F-33000 Bordeaux, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Fagard
mesh_terms: D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification*; D007249:Inflammation / Q000473:pathology*; D019562:Viral Load