title: Treatment interruption in chronically HIV-infected patients with an ultralow HIV reservoir.
abstract: OBJECTIVE
  To investigate the potential for combination antiretroviral therapy (cART)-free remission following analytic treatment interruption (ATI) in chronically HIV-infected patients with ultralow cell-associated DNA.
  
  
  METHODS
  Pilot study of patients (pts) with plasma viral load (pVL) less than 50 copies/ml for more than 2 years on cART, CD4 above 500 cells/μl, CD4/CD8 above 0.9, CD4 nadir above 300 cells/μl and HIV-DNA below 100 copies/10 peripheral blood mononuclear cells (PBMCs), undergoing treatment interruption. Ultrasensitive pVL, CD4 cell count, triplicate HIV-DNA were measured at D0, W2, W4, and every 4 weeks off-ART until W48 and at W4, W12 and W24 after ART resumption (RxR). RxR occurred in case of pVL rebound above 400 copies/ml or CD4 above 400 cells or HIV-related clinical event. The primary endpoint was the percentage of patients who did not reach RxR criteria at W24. Individuals were to be enrolled in three cohorts of five. Enrolment in cohort 2 began if at least one of five patients from cohort 1 remained in success at W8. Cohort 3 did not start.
  
  
  RESULTS
  Ten patients were enrolled, with median (range) CD4 1118 cells/μl (608-1494), CD4/CD8 2.1 (1.4-2.6), HIV-DNA 66 copies/10 PBMC (<66-66) at screening, viral suppression of 4.9 years (2.9-8.3), CD4 nadir 495 cells/μl (330-739). One patient remained off-ART up to W48. Viral rebound occurred in nine of 10 patients at W2 (2 patients), W4 (6 patients) and W12 (one patient). pVL was resuppressed on cART at W4 (8 patients) and W12 (one patient). HIV DNA returned to baseline values within a median of 12 weeks following RxR.
  
  
  CONCLUSIONS
  In a highly selected population of 10 patients with chronic HIV infection, an excellent immune status, durable virological suppression and ultralow reservoir, the success rate of ATI was 10% (95% confidence interval 0.3-44.5%) and nine of 10 patients had prompt rebound of plasma viremia. Resumption of ART led to return to baseline cell-associated total DNA.
authors.affiliation: aAP-HP, Department of Infectious Diseases, Pitié-Salpêtrière University Hospital bSorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136) cDepartment of Immunology, Pitié-Salpêtrière Hospital, Sorbonne Universités, UPMC Univ Paris 06, INSERM, CIMI, UMR_S 1135 dAP-HP, Virology Department, Pitié-Salpêtriêre University Hospital eORVACS, Paris, France. *Chiraz Hamimi and Sidonie Lambert-Niclot contributed equally to the writing of this article. †Details have been provided under Acknowledgements section. ‡Dominique Costagliola and Brigitte Autran contributed equally to the writing of this article.
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Calin
authors.forename: Chiraz
authors.initials: C
authors.lastname: Hamimi
authors.forename: Sidonie
authors.initials: S
authors.lastname: Lambert-Niclot
authors.forename: Guislaine
authors.initials: G
authors.lastname: Carcelain
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bellet
authors.forename: Lambert
authors.initials: L
authors.lastname: Assoumou
authors.forename: Roland
authors.initials: R
authors.lastname: Tubiana
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Dudoit
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006678:HIV / Q000302:isolation & purification*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011533:Proviruses / Q000302:isolation & purification*; D019562:Viral Load; D014766:Viremia; D028761:Withholding Treatment; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents