Date Published: June 19, 2018
Publisher: Lippincott Williams & Wilkins
Author(s): Rachael A. Hughes, Margaret T. May, Kate Tilling, Ninon Taylor, Linda Wittkop, Peter Reiss, John Gill, Philipp Schommers, Dominique Costagliola, Jodie L. Guest, Viviane D. Lima, Antonella d’Arminio Monforte, Colette Smith, Matthias Cavassini, Michael Saag, Jessica L. Castilho, Jonathan A.C. Sterne.
Supplemental Digital Content is available in the text
Combination antiretroviral therapy (ART) has led to substantial increases in the life-expectancy of HIV-positive individuals . Substantial declines in rates of AIDS have led to increased interest in non-AIDS, age-related diseases such as cardiovascular diseases, non-AIDS cancers, kidney disease and neurocognitive decline [2–7], rates of which are higher than in the general population . HIV infection leads to persistent immune activation and inflammation, which may accelerate immunosenescence (deterioration of the immune system due to ageing) . In the general population, a low CD4+ : CD8+ ratio is a surrogate marker for immunosenescence and an independent predictor of all-cause mortality [10,11]. Among HIV-positive individuals, low CD4+ : CD8+ ratio has been associated with higher levels of immunosenescence and inflammation, although the results regarding whether a low or inverted CD4+ : CD8+ ratio predicts non-AIDS-related morbidity and mortality have been conflicting [12,13].
Of 110 098 patients included in ART-CC up to 31 December 2013, 15% were excluded as they started ART before 1998 or before entering the study, 43% without CD4+ or CD8+ measurements within the specified baseline period, and 6% as they had no CD4+ or CD8+ measurement after 6 months since starting ART. Table 1 presents characteristics of the remaining 39 979 eligible patients according to baseline CD4+ cell count. Most were men, approximately 40% were heterosexual and the median age at start of ART was about 40 years. Higher baseline CD4+ cell count predicted higher baseline CD8+ cell count, with substantial reductions in median CD8+ cell count as baseline CD4+ cell count decreased from 100–199 to less than 25 cells/μl.
Using data from a large collaborative study of HIV-infected individuals residing in Europe and North America, we found that, among patients with baseline CD4+ cell count at least 50 cells/μl, predicted mean CD8+ cell counts continued to decrease between 3 and 15 years post-ART, partly driving increases in the predicted mean CD4+ : CD8+ ratio. Lower baseline CD4+ cell count predicted higher increases in the mean CD4+ : CD8+ ratio during the first 6 years since start of ART. Nonetheless, even 15 years since start of ART, the mean CD4+ : CD8+ ratio did not normalize among patients with baseline CD4+ cell count less than 200 cells/μl.
R.A.H. was supported by Medical Research Council grant (MR/J013773/1). J.A.C.S. was supported by grant number MR/J002380/1: this award was jointly funded by the UK Medical Research Council (MRC) 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. He was also supported by National Institute for Health Research Senior Investigator award NF-SI-0611-10168. V.D.L. is funded by a grant from the Canadian Institutes of Health Research (PJT-148595), by a Scholar Award from the Michael Smith Foundation for Health Research and a New Investigator award from the Canadian Institutes of Health Research. J.L.C. was funded by National Institutes of Health grant (NIAID K23AI120875).