Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral Treated People With Human Immunodeficiency Virus (HIV)
Author:
Chammartin Frédérique1ORCID, Mocroft Amanda23, Egle Alexander4, Zangerle Robert5, Smith Colette6, Mussini Cristina7, Wit Ferdinand8, Vehreschild Jörg Janne9, d’Arminio Monforte Antonella10, Castagna Antonella11, Bailly Laurent12, Bogner Johannes13, de Wit Stéphane14, Matulionyte Raimonda15, Law Matthew16, Svedhem Veronica17, Tallada Joan18, Garges Harmony P19, Marongiu Andrea20, Borges Álvaro H221, Jaschinski Nadine2, Neesgaard Bastian2, Ryom Lene222, Bucher Heiner C1, Wit F, van der Valk M, Hillebregt M, Petoumenos K, Law M, Zangerle R, Appoyer H, Stephan C, Bucht M, Chkhartishvili N, Chokoshvili O, d’Arminio Monforte A, Rodano A, Tavelli A, Fanti I, Casabona J, Miro J M, Llibre J M, Riera A, Reyes-Urueña J, Smith C, Lampe F, Sönnerborg A, Falconer K, Svedhem V, Günthard H, Ledergerber B, Bucher H, Kusejko K, Wasmuth J C, Rockstroh J, Vehreschild J J, Fätkenheuer G, Ryom L, Law M, Campo R, De Wit S, Garges H, Günthard H, Lundgren J, McNicholl I, Rooney J, Smith C, Vannappagari V, Wandeler G, Young L, Zangerle R, Lundgren J, Günthard H, Begovac J, Bruguera A, Bucher H, Castagna A, Campo R, Chkhartishvili N, D’Arminio Monforte A, Dedes N, Garges H, Kowalska J, Law M, McNicholl I, Mussini C, Necsoi C, Peters L, Petoumenos K, Pradier C, Raben D, Rockstroh J, Rooney J, Ryom L, Smith C, Sönnerborg A, Stephan C, Vannappagari V, Vehreschild J J, Volny Anne A, Wandeler G, Wasmuth J C, Williams E D, Wit F, Young L, Zangerle R, Ryom L, Mocroft A, Neesgaard B, Greenberg L, Jaschinski N, Timiryasova A, Bansi-Matharu L, Raben D, Peters L, Tusch E, Bannister W, Roen A, Byonanebye D, Fursa O, Pelchen-Matthews A, Reekie J, Svedhem-Johansson V, Van der Valk M, Wit F, Grabmeier-Pfistershammer K, Zangerle R, Hoy J, Bloch M, Braun D, Calmy A, Schüttfort G, Youle M, De Wit S, Mussini C, Zona S, Castagna A, Antinori A, Chkhartishvili N, Bolokadze N, Fontas E, Dollet K, Pradier C, Miro J M, Llibre J M, Vehreschild J J, Schwarze-Zander C, Wasmuth J C, Rockstroh J, Petoumenos K, Hutchinson J, Law M, Begovac J, Duvivier C, Dragovic G, Radoi R, Oprea C, Vasylyev M, Kowalska J, Matulionyte R, Mulabdic V, Marchetti G, Kuzovatova E, Coppola N, Aho I, Martini S, Bucher H, Harxhi A, Wæhre T, Pharris A, Vassilenko A, Fätkenheuer G, Bogner J, Maagaard A, Jablonowska E, Elbirt D, Marrone G, Leen C, Wyen C, Dahlerup Rasmussen L, Hatleberg C, Kundro M, Dedes N, Dixon Williams E, Gallant J, Cohen C, Dunbar M, Marongiu A, Vannappagari V, Garges H, Campo R, Young L, Volny Anne A, Dedes N, Mendao L, Dixon Williams E, Jaschinski N, Neesgaard B, Timiryasova A, Fursa O, Valdenmaier O, Larsen J F, Gardizi M, Raben D, Peters L, Ryom L, Elsing T W, Ramesh Kumar L, Shahi S, Andersen K, Reekie J, Greenberg L, Bansi-Matharu L, Petoumenos K, Byonanebye D, Tusch E, Roen A, Bannister W, Mocroft A,
Affiliation:
1. Division of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel and University of Basel , Basel , Switzerland 2. CHIP, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen , Copenhagen , Denmark 3. Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London , London , United Kingdom 4. Austrian HIV Cohort Study (AHIVCOS), Paracelsus Medical University Hospital , Salzburg , Austria 5. Austrian HIV Cohort Study (AHIVCOS), Medizinische Universität Innsbruck , Innsbruck , Austria 6. The Royal Free HIV Cohort Study, Royal Free Hospital, University College London , London , United Kingdom 7. Modena HIV Cohort, Università degli Studi di Modena , Modena , Italy 8. AIDS Therapy Evaluation in the Netherlands (ATHENA) Cohort, HIV Monitoring Foundation , Amsterdam , The Netherlands 9. Department I of internal Medicine, University Hospital Cologne , Cologne , Germany 10. Italian Cohort Naive Antiretrovirals (ICONA), ASST Santi Paolo e Carlo , Milano , Italy 11. San Raffaele Scientific Institute, Università Vita-Salute San Raffaele , Milano , Italy 12. Nice HIV Cohort, Department of Public Health, Université Côte d’Azur—Centre Hospitalier Universitaire de Nice, UR2CA , Nice , France 13. Division of Infectious Diseases, Medizinische Klinik und Poliklinik IV, LMU University Hospital, LMU Munich , Munich , Germany 14. CHU Saint-Pierre, Centre de Recherche en Maladies Infectieuses a.s.b.l. , Brussels , Belgium 15. Vilnius University, Faculty of Medicine, Department of Infectious Diseases and Dermatovenerology; Vilnius University Hospital Santaros Klinikos , Vilnius , Lithuania 16. The Australian HIV Observational Database (AHOD), Kirby Institute, University of New South Wales , New South Wales , Australia 17. Division of Infectious Diseases, Department of Medicine, Karolinska Institute and Karolinska University Hospital , Stockholm , Sweden 18. European AIDS Treatment Group (EATG) , Brussels , Belgium 19. ViiV Healthcare , Durham, North Carolina , USA 20. Gilead Sciences , Foster City, California , USA 21. Department of Infectious Diseases Immunology, Statens Serum Institut , Copenhagen , Denmark 22. Department of Infectious Diseases 144, Hvidovre University Hospital , Copenhagen , Denmark
Abstract
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.
Funder
Austrian HIV Cohort Study Australian HIV Observational Database CHU Saint-Pierre University Hospital Cologne EuroSIDA Frankfurt HIV Cohort Study Georgian National AIDS Health Information System Modena HIV Cohort San Raffaele Scientific Institute Swiss HIV Cohort Study AIDS Therapy Evaluation in the Netherlands Cohort Royal Free HIV Cohort Study ViiV Healthcare LLC Gilead Sciences Merck Sharp & Dohme US National Institutes of Health National Health and Medical Research Council, Australia
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Microbiology (medical)
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