title: Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized trial.
abstract: BACKGROUND
  As a first step towards HIV cure, we assessed a strategy of antiretroviral therapy (ART) intensification followed by interleukin-7 (IL-7) used as an HIV-reactivating agent.
  
  
  METHODS
  A multicentre, randomized clinical trial included patients on suppressive ART with CD4 cell counts at least 350/μl and HIV-DNA between 10 and 1000 copies/10 peripheral blood mononuclear cells (PBMCs). After an 8-week raltegravir and maraviroc intensification, patients were randomized to intensification alone or with 3 weekly IL-7 injections at weeks 8, 9 and 10. The primary endpoint was at least 0.5 log10 decrease in HIV-DNA in PBMC at W56. Secondary endpoints included ultrasensitive plasma viremia, immunologic changes and safety.
  
  
  RESULTS
  Twenty-nine patients were enrolled with median baseline 558 CD4 cell counts/μl, 360 HIV-DNA copies/10 PBMCs and 12 years on ART. No patient in either arm achieved the primary endpoint. Addition of IL-7 induced a significant expansion of CD4 T cells, primarily central-memory cells (+5%, P = 0.001) at week 12, together with an increase in levels of HIV-DNA/10 PBMC (+0.28 log10 copies/P = 0.001), and the proportion of patients with detectable ultrasensitive plasma HIV-RNA increased compared with week 8 (P = 0.07). At weeks 56 and 80, total and memory CD4 cell counts and total HIV-DNA/ml of blood remained elevated. In contrast, HIV-DNA/million PBMC and plasma viremia returned to baseline levels whereas activated HLA-DRCD4 T cells significantly decreased.
  
  
  CONCLUSIONS
  IL-7 administration and dual ART intensification induced, despite a mild HIV reactivation, an amplification of the HIV reservoir, as a result of central-memory CD4 T-cell expansion, thus limiting this IL-7 based strategy.
  
  
  BACKGROUND
  This trial was registered with ClinicalTrials.gov, number NCT01019551.
authors.affiliation: aAP-HP, Hôpital Pitié-Salpêtrière, Service de Maladies Infectieuses et Tropicales, Paris bSorbonne Universités, UPMC Univ Paris 06 cINSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris dAP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, Paris eORVACS, Hôpital Pitié-Salpêtrière, Paris fINSERM, UMR_S 1135, CIMI, Paris, France gSan Raffaele Scientific Institute, Milan, Italy hIrsi Caixa, Foundation. UAB, UVIC-UCC Hospital 'Germans Trias i Pujol', Badalona, Catalonia, Spain iRoyal Free and University College London Medical School, London, UK jCenter for Global Health and Department of Medicine, Northwestern University, Chicago, Illinois, USA kAP-HP, Hôpital Pitié-Salpêtrière, Service d'immunologie, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Sidonie
authors.initials: S
authors.lastname: Lambert-Niclot
authors.forename: Lambert
authors.initials: L
authors.lastname: Assoumou
authors.forename: Laura
authors.initials: L
authors.lastname: Papagno
authors.forename: François
authors.initials: F
authors.lastname: Lecardonnel
authors.forename: Rima
authors.initials: R
authors.lastname: Zoorob
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tambussi
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Mike
authors.initials: M
authors.lastname: Youle
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Achenbach
authors.forename: Robert L
authors.initials: RL
authors.lastname: Murphy
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D015851:Interleukin-7 / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D019562:Viral Load; D014775:Virus Activation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D007155:Immunologic Factors; D015851:Interleukin-7