Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus
Frédérique Chammartin, Amanda Mocroft, Alexander Egle, Robert Zangerle, Colette Smith, Cristina Mussini, Ferdinand Wit, Jörg Janne Vehreschild, Antonella d’Arminio Monforte, Antonella Castagna, Laurent Bailly, Johannes Bogner, Stéphane De Wit, Raimonda Matulionytė, Matthew Law, Veronica Svedhem, Joan Tallada, H Garges, Andrea Marongiu, Álvaro H. Borges, Nadine Jaschinski, Bastian Neesgaard, Lene Ryom, Heiner C. Bucher, for the RESPOND Study Group, F Wit, Marc van der Valk, M Hillebregt, Kathy Petoumenos, M Law, R Zangerle, H Appoyer, Christoph Stephan, M Bucht, Nikoloz Chkhartishvili, Otar Chokoshvili, Antonella d’Arminio Monforte, A Rodano, A Tavelli, Iuri Fanti, Jordi Casabona, José M. Miró, Josep M. Llibre, Antoni Riéra, Juliana Reyes‐Urueña, C Smith, Fiona Lampe, A Sönnerborg, Karolin Falconer, Veronica Svedhem, Huldrych F. Günthard, Bruno Ledergerber, H Bucher, K Kusejko, J C Wasmuth, Jürgen K. Rockstroh, J J Vehreschild, G Fätkenheuer, L Ryom, Matthew Law, Rafael Campo, Stéphane De Wit, H Garges, Huldrych F. Günthard, Jens Lundgren, Ian R. McNicholl, J Rooney, C Smith, V Vannappagari, Gilles Wandeler, L Young, R Zangerle, Jens Lundgren, Huldrych F. Günthard, J Begovac, Andreu Bruguera, Heiner C. Bucher, A Castagna, Rafael Campo, Nikoloz Chkhartishvili, Antonella d’Arminio Monforte, Nikos Dedes, H Garges, Justyna Kowalska, Matthew Law, Ian R. McNicholl, Cristina Mussini, Coca Necsoi, Lars Peters, Kathy Petoumenos, C Pradier, Dorthe Raben, Jürgen K. Rockstroh, J Rooney, L Ryom, C Smith, A Sönnerborg, Christoph Stephan, V Vannappagari, Jörg Janne Vehreschild
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.