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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

dc.contributor.authorSterling, Timothy R.
dc.contributor.authorSterling, Tim
dc.identifier.citationGras, L., May, M., Ryder, L. P., Trickey, A., Helleberg, M., Obel, N., Thiebaut, R., Guest, J., Gill, J., Crane, H., Dias Lima, V., dʼArminio Monforte, A., Sterling, T. R., Miro, J., Moreno, S., Stephan, C., Smith, C., Tate, J., Shepherd, L., Saag, M., … Antiretroviral Therapy Cohort Collaboration (ART-CC) (2019). 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 (1999), 80(3), 292–300.
dc.descriptionOnly Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at
dc.description.abstractBackground: 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(3). Median CD4: CD8 trajectories did not reach median reference values, even when ART was started at 500 cells/mm(3). Discussion: Starting ART with a CD4 cell count of >= 500 cells/mm3 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.en_US
dc.description.sponsorshipSupported by the UK Medical Research Council (MRC) (Grant number MR/J002380/1) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 programme supported by the European Union. Jonathan Sterne is funded by National Institute for Health Research Senior Investigator award NF-SI-0611-10168. Sources of funding of individual cohorts include the Agence Nationale de Recherche sur le SIDA et les hepatites virales (ANRS), the Institut National de la Sante et de la Recherche Medicale (INSERM), the French, Italian, and Spanish Ministries of Health, the Swiss National Science Foundation (Grant 33CS30_134277), the Ministry of Science and Innovation and the "Spanish Network for AIDS Research" (RIS; ISCIII-RETIC RD06/006), the Stichting HIV Monitoring, which is supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment, the European Commission (EuroCoord Grant 260694), the British Columbia and Alberta Health Services, the National Institutes of Health (NIH) [UW Center for AIDS Research (CFAR) (NIH Grant P30 AI027757), UAB CFAR (NIH Grant P30-AI027767), The Tennessee CFAR (NIH Grant P30 AI110527)], National Institute on Alcohol Abuse and Alcoholism (U10-AA13566, U24-AA020794), the US Department of Veterans Affairs, the Michael Smith Foundation for Health Research, the Canadian Institutes of Health Research, the VHA Office of Research and Development, and unrestricted grants from Abbott, Gilead, Tibotec-Upjohn, ViiV Healthcare, MSD, GlaxoSmithKline, Pfizer, Bristol-Myers Squibb, Roche, and Boehringer-Ingelheim. The Danish HIV Cohort Study is founded by Preben and Anne Simonsens Foundation. J.M.M. received a personal 80: 20 research grant from the Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017-2019. M.H. received funding from the Danish National Research Foundation (Grant number 715). R.G. was supported by the Wellcome Trust (Grant number 106680/Z/14/Z). Data from 13 European cohorts were pooled in June 2014 within COHERE in EuroCoord ( and receives funding from the European Union Seventh Framework Programme (FP7/2007-2013) under EuroCoord grant agreement no 260694.en_US
dc.publisherJAIDS- Journal of Acquired Immune Deficiency Syndromesen_US
dc.rightsCopyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.subjectCD4 cell counten_US
dc.subjectCD8 cell counten_US
dc.subjectCD4:CD8 ratioen_US
dc.subjectantiretroviral therapyen_US
dc.titleDeterminants of Restoration of CD4 and CD8 Cell Counts and Their Ratio in HIV-1-Positive Individuals With Sustained Virological Suppression on Antiretroviral Therapyen_US

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