Reference curves for CD4 T-cell count response to combination antiretroviral therapy in HIV-1-infected treatment-naïve patients.
The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy (cART) in HIV-1-infected patients.



All patients in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) cohort who were aged ≥ 18 years and started cART for the first time between 1 January 2005 and 1 January 2010 and who had at least one available measurement of CD4 count and a viral load ≤ 50 HIV-1 RNA copies/mL at 6 months (± 3 months) after cART initiation were included in the study. Unadjusted and adjusted references curves and predictions were obtained using quantile regressions.



A total of 28 992 patients were included in the study. The median CD4 T-cell count at treatment initiation was 249 [interquartile range (IQR) 150, 336] cells/μL. The median observed CD4 counts at 6, 9 and 12 months were 382 (IQR 256, 515), 402 (IQR 274, 543) and 420 (IQR 293, 565) cells/μL. The two main factors explaining the variation of CD4 count at 6 months were AIDS stage and CD4 count at cART initiation. A CD4 count increase of ≥ 100 cells/mL is generally required in order that patients stay 'on track' (i.e. with a CD4 count at the same percentile as when they started), with slightly higher gains required for those starting with CD4 counts in the higher percentiles. Individual predictions adjusted for factors influencing CD4 count were more precise.



Reference curves aid the evaluation of the immune response early after antiretroviral therapy initiation that leads to viral control.
CIC 1401, CHU de Bordeaux, Bordeaux, France.|INSERM U1219 - Centre Inserm Bordeaux Population Health, Université de Bordeaux, Bordeaux, France.|ISPED, Centre INSERM U1219-Bordeaux Population Health, Université de Bordeaux, Bordeaux, France.
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V
Bouteloup
Research Department of Infection & Population Health, UCL, London, UK.
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C
Sabin
Research Department of Infection & Population Health, UCL, London, UK.
A
A
Mocroft
Stichting HIV Monitoring, Amsterdam, The Netherlands.
L
L
Gras
Department of Hygiene, Epidemiology & Medical Statistics, Athens University Medical School, Athens, Greece.
N
N
Pantazis
Montpellier University, Montpellier, France.
V
V
Le Moing
Infectious Diseases Unit, Department of Health Sciences, San Paolo University Hospital, Milan, Italy.
A
A
d'Arminio Monforte
INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), UPMC Univ Paris 06, Sorbonne Universités, F-75013, Paris, France.
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M
Mary-Krause
Hospital General of Castellon, Castellón, Spain.
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B
Roca
Infectious Diseases Service. Hospital Clinic - IDIBAPS, University of Barcelona, Barcelona, Spain.
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JM
Miro
Division of Infectious Diseases and Hospital Epidemiology, Department of Clinical Research, University Hospital of Basel, Basel, Switzerland.
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M
Battegay
Department of Dermatology, Venerology - Center for Sexual Health and Medicine, Ruhr-Universität Bochum, Bochum, Germany.
N
N
Brockmeyer
Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.
J
J
Berenguer
INSERM U1219 - Centre Inserm Bordeaux Population Health, Université de Bordeaux, Bordeaux, France.|Service de Médecine Interne et Maladies Infectieuses, Hôpital Saint-André, Bordeaux, France.
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P
Morlat
Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.
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N
Obel
Department of Infectious Diseases, St Pierre University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
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S
De Wit
Department of Internal Medicine, University of Cologne and German Centre for Infection Research (DZIF), Cologne, Germany.
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G
Fätkenheuer
Medical University Innsbruck, Innsbruck, Austria.
R
R
Zangerle
APHP, Unité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Centre Hospitalier Universitaire Hôtel Dieu, Paris, France.|Faculté de Médecine Site Necker, Sorbonne Paris Cité, Université Paris Descartes, EA 7327, Paris, France.
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J
Ghosn
Vall d'Hebrón Institut de Recerca (VHIR), Barcelona, Spain.|Universitat Autònoma de Barcelona, Barcelona, Spain.
S
S
Pérez-Hoyos
CHIP, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
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M
Campbell
Division of Infectious Diseases, Department of Internal Medicine, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, The Netherlands.|Department of Infectious Diseases, Public Health Service, Amsterdam, The Netherlands.
M
M
Prins
CIC 1401, CHU de Bordeaux, Bordeaux, France.|INSERM U1219 - Centre Inserm Bordeaux Population Health, Université de Bordeaux, Bordeaux, France.|ISPED, Centre INSERM U1219-Bordeaux Population Health, Université de Bordeaux, Bordeaux, France.|CHU de Bordeaux, Pole de Sante Publique, Service d'Information Medicale, F-33000, Bordeaux, France.
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G
Chêne
INSERM, U1018, Epidemiology of HIV, Reproduction, Paediatrics, CESP; University Paris-Sud, Paris, France.|Department of Public Health and Epidemiology, Bicêtre Hospital, AP-HP, Le Kremlin Bicêtre, Paris, France.
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L
Meyer
Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
M
M
Dorrucci
Unit of Infectious and Tropical Diseases, Department of Medical and Surgical Sciences, University "Magna Graecia", Catanzaro, Italy.
C
C
Torti
INSERM U1219 - Centre Inserm Bordeaux Population Health, Université de Bordeaux, Bordeaux, France.|ISPED, Centre INSERM U1219-Bordeaux Population Health, Université de Bordeaux, Bordeaux, France.|CHU de Bordeaux, Pole de Sante Publique, Service d'Information Medicale, F-33000, Bordeaux, France.
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Thiébaut
D000293:Adolescent; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D016903:Drug Monitoring; D005060:Europe; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
D044966:Anti-Retroviral Agents
CD4 response; HIV monitoring; antiretroviral treatment monitoring; longitudinal data