Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: A randomized trial

Christine Katlama*, Sidonie Lambert-Niclot, Lambert Assoumou, Laura Papagno, Francois Lecardonnel, Rima Zoorob, Giuseppe Tambussi, Bonaventura Clotet, Mike Youle, Chad J. Achenbach, Robert L. Murphy, Vincent Calvez, Dominique Costagliola, Brigitte Autran

*Corresponding author for this work

Research output: Contribution to journalArticle

39 Scopus citations

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/ml and HIV-DNA between 10 and 1000 copies/106 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/ml, 360 HIV-DNA copies/106 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/106 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 HLADR+CD4+ T cells significantly decreased. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)221-230
Number of pages10
JournalAIDS
Volume30
Issue number2
DOIs
StatePublished - Jan 1 2016

Keywords

  • Antiretroviral therapy intensification
  • HIV DNA
  • HIV cure
  • HIV eradication
  • immune modulation
  • interleukin-7
  • maraviroc
  • raltegravir

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: A randomized trial'. Together they form a unique fingerprint.

  • Cite this

    Katlama, C., Lambert-Niclot, S., Assoumou, L., Papagno, L., Lecardonnel, F., Zoorob, R., Tambussi, G., Clotet, B., Youle, M., Achenbach, C. J., Murphy, R. L., Calvez, V., Costagliola, D., & Autran, B. (2016). Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: A randomized trial. AIDS, 30(2), 221-230. https://doi.org/10.1097/QAD.0000000000000894