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

Luuk Gras, Margaret May, Lars Peter Ryder, Adam Trickey, 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 SaagArmin Rieger, Daniel Gillor, Matthias Cavassini, Marta Montero, Suzanne Ingle, Peter Reiss, Dominique Costagliola, Ferdinand W N M Wit, Jonathan Sterne, Frank de Wolf, Ronald Geskus, The Antiretroviral Therapy Cohort Collaboration (ART-CC)

Research output: Contribution to journalArticle (Academic Journal)peer-review

1 Citation (Scopus)
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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.

Original languageEnglish
Pages (from-to)292-300
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Issue number3
Early online date1 Mar 2019
Publication statusPublished - Mar 2019


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

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