Determinants of Restoration of CD4 and CD8 Cell Counts and Their Ratio in HIV-1–Positive Individuals With Sustained Virological Suppression on Antiretroviral Therapy. (1st March 2019)

• Record Type: Journal Article
• Authors: Gras, Luuk; May, Margaret; Ryder, Lars Peter; Trickey, Adam; Helleberg, Marie; Obel, Niels; Thiebaut, Rodolphe; Guest, Jodie; Gill, John; Crane, Heidi; Dias Lima, Viviane; d'Arminio Monforte, Antonella; Sterling, Timothy R.; Miro, Jose; Moreno, Santiago; Stephan, Christoph; Smith, Colette; Tate, Janet; Shepherd, Leah; Saag, Mike; Rieger, Armin; Gillor, Daniel; Cavassini, Matthias; Montero, Marta; Ingle, Suzanne M.; Reiss, Peter; Costagliola, Dominique; Wit, Ferdinand W.N.M.; Sterne, Jonathan; de Wolf, Frank; Geskus, Ronald;
• Is Part Of: Journal of acquired immune deficiency syndromes. Volume 80:Number 3(2019)
• Publication Date: 2019-03-01
• Subjects: CD4 cell count -- CD8 cell count -- CD4:CD8 ratio -- antiretroviral therapy -- HIV -- age; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome -- Periodicals; AIDS (Disease); Periodicals; 616.9792005
• DOI: 10.1097/QAI.0000000000001913
• Languages: English
• ISSNs: 1525-4135

Abstract

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 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/mm 3 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. Abstract : Supplemental Digital Content is Available in the Text.