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Determinants of Restoration of CD4 and CD8 Cell Counts and their Ratio in HIV-1 Positive Individuals with Sustained Virological Suppression on Antiretroviral Therapy

Research output: Contribution to journalArticle

  • Luuk Gras
  • Margaret May
  • Lars Peter Ryder
  • Adam Trickeyhttp://orcid.org/0000-0003-3462-2898
  • Marie Helleberg
  • Niels Obel
  • Rodolphe Thiébaut
  • Jodie Guest
  • M John Gill
  • Heidi M Crane
  • Viviane D. Lima
  • Antonella D Arminio Monforte
  • Timothy R Sterling
  • Jose Miro
  • Santiago Moreno
  • Christoph Stephan
  • Colette Smith
  • Janet P Tate
  • Leah Shepherd
  • M Saag
  • Armin Rieger
  • Daniel Gillor
  • Matthias Cavassini
  • Marta Montero
  • Suzanne Ingle
  • Peter Reiss
  • Dominique Costagliola
  • Ferdinand W N M Wit
  • Jonathan Sternehttp://orcid.org/0000-0001-8496-6053
  • Frank de Wolf
  • Ronald Geskus
  • The Antiretroviral Therapy Cohort Collaboration (ART-CC)
Original languageEnglish
Pages (from-to)292-300
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume80
Issue number3
Early online date1 Mar 2019
DOIs
DateAccepted/In press - 15 Oct 2018
DateE-pub ahead of print - 1 Mar 2019
DatePublished (current) - Mar 2019

Abstract

BACKGROUND: An increasing number of HIV-positive individuals now start antiretroviral therapy (ART) with high CD4 cell counts. We investigated whether this makes restoration of CD4 and CD8 cell counts and the CD4:CD8 ratio during virologically suppressive ART to median levels seen in HIV-uninfected individuals more likely and whether restoration depends on gender, age, and other individual characteristics.

METHODS: We determined median and quartile reference values for CD4 and CD8 cell counts and their ratio using cross-sectional data from 2309 HIV-negative individuals. We used longitudinal measurements of 60,997 HIV-positive individuals from the Antiretroviral Therapy Cohort Collaboration in linear mixed-effects models.

RESULTS: When baseline CD4 cell counts were higher, higher long-term CD4 cell counts and CD4:CD8 ratios were reached. Highest long-term CD4 cell counts were observed in middle-aged individuals. During the first 2 years, median CD8 cell counts converged toward median reference values. However, changes were small thereafter and long-term CD8 cell count levels were higher than median reference values. Median 8-year CD8 cell counts were higher when ART was started with <250 CD4 cells/mm. Median CD4:CD8 trajectories did not reach median reference values, even when ART was started at 500 cells/mm.

DISCUSSION: Starting ART with a CD4 cell count of ≥500 cells/mm makes reaching median reference CD4 cell counts more likely. However, median CD4:CD8 ratio trajectories remained below the median levels of HIV-negative individuals because of persisting high CD8 cell counts. To what extent these subnormal immunological responses affect specific clinical endpoints requires further investigation.

    Research areas

  • CD4 cell count, CD8 cell count, CD4:CD8 ratio, antiretroviral therapy, HIV, age

Documents

Documents

  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Wolters Kluwer at https://journals.lww.com/jaids/fulltext/2019/03010/Determinants_of_Restoration_of_CD4_and_CD8_Cell.9.aspx . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 603 KB, PDF document

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  • Supplementary information DOC Figures

    Accepted author manuscript, 1 MB, Word document

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  • Supplementary information PDF SDC results

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  • Supplementary information DOC Tables

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