학술논문
Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus.
Document Type
Article
Author
Chammartin, Frédérique; Mocroft, Amanda; Egle, Alexander; Zangerle, Robert; Smith, Colette; Mussini, Cristina; Wit, Ferdinand; Vehreschild, Jörg Janne; Monforte, Antonella d'Arminio; Castagna, Antonella; Bailly, Laurent; Bogner, Johannes; Wit, Stéphane de; Matulionyte, Raimonda; Law, Matthew; Svedhem, Veronica; Tallada, Joan; Garges, Harmony P; Marongiu, Andrea; Borges, Álvaro H
Source
Subject
*RISK assessment
*ANTIRETROVIRAL agents
*T cells
*VIRAL load
*RESEARCH funding
*CD4 lymphocyte count
*SCIENTIFIC observation
*HIV infections
*DESCRIPTIVE statistics
*PSYCHOLOGY of HIV-positive persons
*TUMORS
*CONFIDENCE intervals
*AIDS
*PROPORTIONAL hazards models
*DISEASE complications
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Language
ISSN
1058-4838
Abstract
Background Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear. Methods We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality. Results CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10–6.19] and 2.03 [95% CI 1.24–3.33], respectively). CD4 cell counts below 350 cells/μL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies. Conclusions In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM. [ABSTRACT FROM AUTHOR]