Fabienne Caby1,2, Marguerite Guiguet2, Laurence Weiss3, Alan Winston4, Jose M Miro5, Deborah Konopnicki6, Vincent Le Moing7, Fabrice Bonnet8, Peter Reiss9, Cristina Mussini10, Isabelle Poizot-Martin11, Ninon Taylor12, Athanasios Skoutelis13, Laurence Meyer14, Cécile Goujard15, Barbara Bartmeyer16, Christoph Boesecke17, Andrea Antinori18, Eugenia Quiros-Roldan19, Linda Wittkop20,21, Casper Frederiksen22, Antonella Castagna23, Maria Christine Thurnheer24, Veronica Svedhem25, Sophie Jose26, Dominique Costagliola2, Murielle Mary-Krause2, Sophie Grabar2,27. 1. Unité VIH-IST, Service d'Immuno-Hématologie, Hôpital Victor Dupouy, Argenteuil, France. 2. Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP), Paris, France. 3. Université de Paris, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris Centre Hôtel Dieu, Paris, France. 4. Department of Infectious Disease, Imperial College London, London, United Kingdom. 5. Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain. 6. St Pierre University Hospital, Université Libre de Bruxelles, Bruxelles, Belgium. 7. Department of Infectious Disease, University Hospital of Montpellier, Montpellier, France. 8. CHU de Bordeaux and INSERM U1219, ISPED, Université de Bordeaux, Bordeaux, France. 9. HIV Monitoring Foundation, Amsterdam, The Netherlands, and Department of Global Health, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 10. University of Modena and Reggio Emilia, Modena, Italy. 11. Aix Marseille Université, APHM, INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, Hôpital Sainte- Marguerite, Service d'Immuno-hématologie clinique, Marseille, France. 12. Department of Dermatology, Paracelsus Private Medical University Salzburg, Salzburg, Austria. 13. 5th Department of Medicine and Infectious Diseases "Evangelismos" General Hospital of Athens, Athens, Greece. 14. INSERM CESP U1018, Université Paris-Saclay, APHP Bicêtre Hospital, Le Kremlin-Bicêtre, France. 15. Service de Médecine interne et d'Immunologie clinique, AP-HP Université Paris-Saclay, Hôpital Bicêtre, Faculté de Médecine-Université Paris-Saclay, Centre de recherche en épidémiologie et santé des populations CESP-Inserm U1018, Le Kremlin Bicêtre, France. 16. Robert Koch Institute, Department of Infectious Disease Epidemiology, Berlin, Germany. 17. German Centre for Infection Research, Cologne-Bonn; Department of Medicine I, Bonn University Hospital, Bonn, Germany. 18. HIV/AIDS Department, National Institute for Infectious Diseases, Lazzaro Spallanzani, IRCCS, Rome, Italy. 19. Department of Infectious and Tropical Diseases, Universitá degli Studi di Brescia, ASST Spedali Civili di Brescia, Brescia, Italy. 20. Université Bordeaux, ISPED, Inserm, Bordeaux Population Health Research Center, Team MORPH3EUS, UMR 1219, Bordeaux, France. 21. CHU de Bordeaux, Pôle de santé publique, Service d'information médicale, Bordeaux, France. 22. University of Copenhagen, Section of Forensic Genetics, Copenhagen, Denmark. 23. Vita-Salute San Raffaele University, IRCC San Raffaele, Milan, Italy. 24. Division of Infectious Diseases, University Hospital Berne, University of Berne, Berne, Switzerland. 25. Department of Infectious Diseases, Karolinska University Hospital and Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden. 26. Transforming Cancer Services Team-Public Health England Partnership, National Cancer Registration and Analysis Service, Wellington House, London United Kingdom. 27. Université de Paris, Assistance Publique-Hôpitaux de Paris (AP-HP), Unité de Biostatistique et Epidémiologie, Hôpital cochin, Paris, France.
Abstract
BACKGROUND: A persistently low CD4/CD8 ratio has been reported to inversely correlate with the risk of non-AIDS defining cancer in people living with human immunodeficiency virus (HIV; PLWH) efficiently treated by combination antiretroviral therapy (cART). We evaluated the impact of the CD4/CD8 ratio on the risk of Kaposi sarcoma (KS) or non-Hodgkin lymphoma (NHL), still among the most frequent cancers in treated PLWH. METHODS: PLWH from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) were included if they achieved virological control (viral load ≤ 500 copies/mL) within 9 months following cART and without previous KS/LNH diagnosis. Cox models were used to identify factors associated with KS or NHL risk, in all participants and those with CD4 ≥ 500/mm3 at virological control. We analyzed the CD4/CD8 ratio, CD4 count and CD8 count as time-dependent variables, using spline transformations. RESULTS: We included 56 708 PLWH, enrolled between 2000 and 2014. At virological control, the median (interquartile range [IQR]) CD4 count, CD8 count, and CD4/CD8 ratio were 414 (296-552)/mm3, 936 (670-1304)/mm3, and 0.43 (0.28-0.65), respectively. Overall, 221 KS and 187 NHL were diagnosed 9 (2-37) and 18 (7-42) months after virological control. Low CD4/CD8 ratios were associated with KS risk (hazard ratio [HR] = 2.02 [95% confidence interval {CI } = 1.23-3.31]) when comparing CD4/CD8 = 0.3 to CD4/CD8 = 1) but not with NHL risk. High CD8 counts were associated with higher NHL risk (HR = 3.14 [95% CI = 1.58-6.22]) when comparing CD8 = 3000/mm3 to CD8 = 1000/mm3). Similar results with increased associations were found in PLWH with CD4 ≥ 500/mm3 at virological control (HR = 3.27 [95% CI = 1.60-6.56] for KS; HR = 5.28 [95% CI = 2.17-12.83] for NHL). CONCLUSIONS: Low CD4/CD8 ratios and high CD8 counts despite effective cART were associated with increased KS/NHL risks respectively, especially when CD4 ≥ 500/mm3.
BACKGROUND: A persistently low CD4/CD8 ratio has been reported to inversely correlate with the risk of non-AIDS defining cancer in people living with human immunodeficiency virus (HIV; PLWH) efficiently treated by combination antiretroviral therapy (cART). We evaluated the impact of the CD4/CD8 ratio on the risk of Kaposi sarcoma (KS) or non-Hodgkin lymphoma (NHL), still among the most frequent cancers in treated PLWH. METHODS: PLWH from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) were included if they achieved virological control (viral load ≤ 500 copies/mL) within 9 months following cART and without previous KS/LNH diagnosis. Cox models were used to identify factors associated with KS or NHL risk, in all participants and those with CD4 ≥ 500/mm3 at virological control. We analyzed the CD4/CD8 ratio, CD4 count and CD8 count as time-dependent variables, using spline transformations. RESULTS: We included 56 708 PLWH, enrolled between 2000 and 2014. At virological control, the median (interquartile range [IQR]) CD4 count, CD8 count, and CD4/CD8 ratio were 414 (296-552)/mm3, 936 (670-1304)/mm3, and 0.43 (0.28-0.65), respectively. Overall, 221 KS and 187 NHL were diagnosed 9 (2-37) and 18 (7-42) months after virological control. Low CD4/CD8 ratios were associated with KS risk (hazard ratio [HR] = 2.02 [95% confidence interval {CI } = 1.23-3.31]) when comparing CD4/CD8 = 0.3 to CD4/CD8 = 1) but not with NHL risk. High CD8 counts were associated with higher NHL risk (HR = 3.14 [95% CI = 1.58-6.22]) when comparing CD8 = 3000/mm3 to CD8 = 1000/mm3). Similar results with increased associations were found in PLWH with CD4 ≥ 500/mm3 at virological control (HR = 3.27 [95% CI = 1.60-6.56] for KS; HR = 5.28 [95% CI = 2.17-12.83] for NHL). CONCLUSIONS: Low CD4/CD8 ratios and high CD8 counts despite effective cART were associated with increased KS/NHL risks respectively, especially when CD4 ≥ 500/mm3.