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CD4:CD8 lymphocyte ratio as a quantitative measure of immunologic health in HIV-1 infection: findings from an African cohort with prospective data

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Last modified
  • 02/20/2025
Type of Material
Authors
    Jianming Tang, University of Alabama at BirminghamXuelin Li, University of Alabama at BirminghamMatthew A. Price, University of California San FranciscoEduard J. Sanders, University of OxfordOmu Anzala, Kenya AIDS Vaccine InitiativeEtienne Karita, Projet San FranciscoAnatoli Kamali, Uganda Virus Research InstituteShabir Lakhi, Zambia-Emory HIV Research ProjectSusan Allen, Emory UniversityEric Hunter, Emory UniversityRichard A. Kaslow, University of Alabama at BirminghamJill Gilmour, Chelsea and Westminster Hospital
Language
  • English
Date
  • 2015-07
Publisher
  • Frontiers Media
Publication Version
Copyright Statement
  • © 2015 Tang, Li, Price, Sanders, Anzala, Karita, Kamali, Lakhi, Allen, Hunter, Kaslow and Gilmour.
License
Final Published Version (URL)
Title of Journal or Parent Work
ISSN
  • 1664-302X
Volume
  • 6
Grant/Funding Information
  • The full list of IAVI donors is available at www.iavi.org.
  • Additional funding for this work came from (i) the United States National Institute of Allergy and Infectious Diseases (NIAID), through two R01 grants (AI071906 to RK/JT and AI064060 to EH), (ii) the Fogarty AIDS International Training and Research Program (AITRP; grant FIC 2D43 TW001042 to SL), and (iii) the KEMRI-Wellcome Trust Research Programme at the Centre for Geographical Medicine Research-Kilifi (Wellcome Trust award #077092).
  • This work was funded in part by IAVI and made possible by the generous support from many donors, including: the Bill & Melinda Gates Foundation, the Ministry of Foreign Affairs of Denmark, Irish Aid, the Ministry of Finance of Japan, the Ministry of Foreign Affairs of the Netherlands, the Norwegian Agency for Development Cooperation, the United Kingdom Department for International Development, and the United States Agency for International Development (USAID).
Supplemental Material (URL)
Abstract
  • In individuals with human immunodeficiency virus type 1 (HIV-1) infection, CD4:CD8 lymphocyte ratio is often recognized as a quantitative outcome that reflects the critical role of both CD4+ and CD8+ T-cells in HIV-1 pathogenesis or disease progression. Our work aimed to first establish the dynamics and clinical relevance of CD4:CD8 ratio in a cohort of native Africans and then to examine its association with viral and host factors, including: (i) length of infection, (ii) demographics, (iii) HIV-1 viral load (VL), (iv) change in CD4+ T-lymphocyte count (CD4 slope), (v) HIV-1 subtype, and (vi) host genetics, especially human leukocyte antigen (HLA) variants. Data from 499 HIV-1 seroconverters with frequent (monthly to quarterly) follow-up revealed that CD4:CD8 ratio was stable in the first 3 years of infection, with a modest correlation with VL and CD4 slope. A relatively normal CD4:CD8 ratio (>1.0) in early infection was associated with a substantial delay in disease progression to severe immunodeficiency (<350 CD4 cells/μl), regardless of other correlates of HIV-1 pathogenesis (adjusted hazards ratio (HR) = 0.43, 95% confidence interval (CI) = 0.29-0.63, P < 0.0001). Low VL (<10,000 copies/ml) and HLA-A*74:01 were the main predictors of CD4:CD8 ratio >1.0, but HLA variants (e.g., HLA-B*57 and HLA-B*81) previously associated with VL and/or CD4 trajectories in eastern and southern Africans had no obvious impact on CD4:CD8 ratio. Collectively, these findings suggest that CD4:CD8 ratio is a robust measure of immunologic health with both clinical and epidemiological implications.
Author Notes
  • Correspondence: Jianming Tang, Department of Medicine, University of Alabama at Birmingham, 1665 University Boulevard, RPHB634, Birmingham, AL 35294,USA; jtang@uab.edu
Keywords
Research Categories
  • Health Sciences, Epidemiology
  • Health Sciences, Immunology
  • Biology, Virology

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