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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

Gras, L; May, M; Ryder, LP; Trickey, A; Helleberg, M; Obel, N; Thiebaut, R; ... Geskus, R; + view all (2018) Determinants of Restoration of CD4 and CD8 Cell Counts and their Ratio in HIV-1 Positive Individuals with Sustained Virological Suppression on Antiretroviral Therapy. JAIDS Journal of Acquired Immune Deficiency Syndromes 10.1097/QAI.0000000000001913. (In press). Green open access

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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 count and their ratio using cross-sectional data from 2,309 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 two years median CD8 cell counts converged towards 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 have impact on specific clinical endpoints requires further investigation.

Type: Article
Title: Determinants of Restoration of CD4 and CD8 Cell Counts and their Ratio in HIV-1 Positive Individuals with Sustained Virological Suppression on Antiretroviral Therapy
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/QAI.0000000000001913
Publisher version: http://doi.org/10.1097/QAI.0000000000001913
Language: English
Additional information: © 2018 Wolters Kluwer Health. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (https://creativecommons.org/licenses/by/4.0/).
Keywords: CD4 cell count, CD8 cell count, CD4:CD8 ratio, antiretroviral therapy, HIV, age
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health
URI: https://discovery.ucl.ac.uk/id/eprint/10064404
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