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 1 Margaret May 2 Lars Ryder 3, 4 Adam Trickey 2 Marie Helleberg 4, 3 Niels Obel 3 Rodolphe Thiébaut 5, 6 Jodie Guest 7 John Gill 8 Heidi Crane 9 Viviane Dias Lima 10, 11 Antonella Dʼarminio Monforte 12 Timothy Sterling 13 Jose Miró 14, 15 Santiago Moreno 16 Christoph Stephan 17, 18 Colette Smith 19 Janet Tate 20 Leah Shepherd 19 Mike Saag 21 Armin Rieger 22 Daniel Gillor 23 Matthias Cavassini 24, 25 Marta Montero 26 Suzanne Ingle 2 Peter Reiss 1, 27 Dominique Costagliola 28, 29 Ferdinand W.N.M. Wit 27, 1, 30 Jonathan Sterne 2 Frank de Wolf 31 Ronald Geskus 32, 33, 27
5 SISTM - Statistics In System biology and Translational Medicine
Epidémiologie et Biostatistique [Bordeaux], Inria Bordeaux - Sud-Ouest
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.
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Luuk Gras, Margaret May, Lars Ryder, Adam Trickey, Marie Helleberg, et al.. Determinants of Restoration of CD4 and CD8 Cell Counts and Their Ratio in HIV-1-Positive Individuals With Sustained Virological Suppression on Antiretroviral Therapy. Journal of Acquired Immune Deficiency Syndromes, Lippincott, Williams & Wilkins, 2019, 80 (3), pp.292-300. ⟨10.1097/QAI.0000000000001913⟩. ⟨hal-02279469⟩

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