CD4/CD8 Ratio and the Risk of Kaposi Sarcoma or Non-Hodgkin Lymphoma in the Context of Efficiently Treated Human Immunodeficiency Virus (HIV) Infection: A Collaborative Analysis of 20 European Cohort Studies.


Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
01 07 2021
Historique:
received: 08 03 2020
accepted: 03 08 2020
entrez: 9 8 2021
pubmed: 10 8 2021
medline: 23 9 2021
Statut: ppublish

Résumé

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. 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. 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). Low CD4/CD8 ratios and high CD8 counts despite effective cART were associated with increased KS/NHL risks respectively, especially when CD4 ≥ 500/mm3.

Sections du résumé

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.

Identifiants

pubmed: 34370842
pii: 5880596
doi: 10.1093/cid/ciaa1137
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

50-59

Subventions

Organisme : Medical Research Council
ID : MC_UU_00004/03
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M004236/1
Pays : United Kingdom
Organisme : Agence Nationale de Recherches sur le Sida et les Hépatites Virales

Investigateurs

Ali Judd (A)
Robert Zangerle (R)
Giota Touloumi (G)
Josiane Warszawski (J)
Laurence Meyer (L)
François Dabis (F)
Murielle Mary Krause (MM)
Jade Ghosn (J)
Catherine Leport (C)
Linda Wittkop (L)
Peter Reiss (P)
Ferdinand Wit (F)
Maria Prins (M)
Heiner Bucher (H)
Diana Gibb (D)
Gerd Fätkenheuer (G)
Julia Del Amo (J)
Niels Obel (N)
Claire Thorne (C)
Amanda Mocroft (A)
Ole Kirk (O)
Christoph Stephan (C)
Santiago Pérez-Hoyos (S)
Osamah Hamouda (O)
Barbara Bartmeyer (B)
Nikoloz Chkhartishvili (N)
Antoni Noguera-Julian (A)
Andrea Antinori (A)
Antonella d'Arminio Monforte (AD)
Norbert Brockmeyer (N)
Luis Prieto (L)
Pablo Rojo Conejo (PR)
Antoni Soriano-Arandes (A)
Manuel Battegay (M)
Roger Kouyos (R)
Cristina Mussini (C)
Jordi Casabona (J)
Jose M Miró (JM)
Antonella Castagna (A)
Deborah Konopnick (D)
Tessa Goetghebuer (T)
Anders Sönnerborg (A)
Carlo Torti (C)
Caroline Sabin (C)
Ramon Teira (R)
Myriam Garrido (M)
David Haerry (D)

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Auteurs

Fabienne Caby (F)

Unité VIH-IST, Service d'Immuno-Hématologie, Hôpital Victor Dupouy, Argenteuil, France.
Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP), Paris, France.

Marguerite Guiguet (M)

Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP), Paris, France.

Laurence Weiss (L)

Université de Paris, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris Centre Hôtel Dieu, Paris, France.

Alan Winston (A)

Department of Infectious Disease, Imperial College London, London, United Kingdom.

Jose M Miro (JM)

Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.

Deborah Konopnicki (D)

St Pierre University Hospital, Université Libre de Bruxelles, Bruxelles, Belgium.

Vincent Le Moing (V)

Department of Infectious Disease, University Hospital of Montpellier, Montpellier, France.

Fabrice Bonnet (F)

CHU de Bordeaux and INSERM U1219, ISPED, Université de Bordeaux, Bordeaux, France.

Peter Reiss (P)

HIV Monitoring Foundation, Amsterdam, The Netherlands, and Department of Global Health, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Cristina Mussini (C)

University of Modena and Reggio Emilia, Modena, Italy.

Isabelle Poizot-Martin (I)

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.

Ninon Taylor (N)

Department of Dermatology, Paracelsus Private Medical University Salzburg, Salzburg, Austria.

Athanasios Skoutelis (A)

5th Department of Medicine and Infectious Diseases "Evangelismos" General Hospital of Athens, Athens, Greece.

Laurence Meyer (L)

INSERM CESP U1018, Université Paris-Saclay, APHP Bicêtre Hospital, Le Kremlin-Bicêtre, France.

Cécile Goujard (C)

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.

Barbara Bartmeyer (B)

Robert Koch Institute, Department of Infectious Disease Epidemiology, Berlin, Germany.

Christoph Boesecke (C)

German Centre for Infection Research, Cologne-Bonn; Department of Medicine I, Bonn University Hospital, Bonn, Germany.

Andrea Antinori (A)

HIV/AIDS Department, National Institute for Infectious Diseases, Lazzaro Spallanzani, IRCCS, Rome, Italy.

Eugenia Quiros-Roldan (E)

Department of Infectious and Tropical Diseases, Universitá degli Studi di Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.

Linda Wittkop (L)

Université Bordeaux, ISPED, Inserm, Bordeaux Population Health Research Center, Team MORPH3EUS, UMR 1219, Bordeaux, France.
CHU de Bordeaux, Pôle de santé publique, Service d'information médicale, Bordeaux, France.

Casper Frederiksen (C)

University of Copenhagen, Section of Forensic Genetics, Copenhagen, Denmark.

Antonella Castagna (A)

Vita-Salute San Raffaele University, IRCC San Raffaele, Milan, Italy.

Maria Christine Thurnheer (MC)

Division of Infectious Diseases, University Hospital Berne, University of Berne, Berne, Switzerland.

Veronica Svedhem (V)

Department of Infectious Diseases, Karolinska University Hospital and Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.

Sophie Jose (S)

Transforming Cancer Services Team-Public Health England Partnership, National Cancer Registration and Analysis Service, Wellington House, London United Kingdom.

Dominique Costagliola (D)

Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP), Paris, France.

Murielle Mary-Krause (M)

Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP), Paris, France.

Sophie Grabar (S)

Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP), Paris, France.
Université de Paris, Assistance Publique-Hôpitaux de Paris (AP-HP), Unité de Biostatistique et Epidémiologie, Hôpital cochin, Paris, France.

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