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 Matulionyte; Matthew Law; Veronica Svedhem; Joan Tallada; Harmony P Garges; Andrea Marongiu; Álvaro H Borges; Nadine Jaschinski; Bastian Neesgaard; Lene Ryom; Heiner C Bucher; RESPOND Study Group

doi:10.1093/cid/ciad671

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 Matulionyte, Matthew Law, Veronica Svedhem, Joan Tallada, Harmony P Garges, Andrea Marongiu, Álvaro H BorgesNadine Jaschinski, Bastian Neesgaard, Lene Ryom, Heiner C Bucher, RESPOND Study Group

^*Corresponding author for this work

23 Citations (Scopus)

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.

Original language	English
Journal	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume	78
Issue number	4
Pages (from-to)	995-1004
Number of pages	10
ISSN	1058-4838
DOIs	https://doi.org/10.1093/cid/ciad671
Publication status	Published - 10 Apr 2024

Keywords

Acquired Immunodeficiency Syndrome/complications
Anti-HIV Agents/adverse effects
Anti-Retroviral Agents/therapeutic use
CD4 Lymphocyte Count
CD4-CD8 Ratio
HIV
HIV Infections/complications
Humans
Neoplasms/complications
Viral Load
malignancy
antiretroviral therapy
CD4:CD8 ratio
observational study
HIV infection

Access to Document

10.1093/cid/ciad671

Cite this

Chammartin, F., Mocroft, A., Egle, A., Zangerle, R., Smith, C., Mussini, C., Wit, F., Vehreschild, J. J., d'Arminio Monforte, A., Castagna, A., Bailly, L., Bogner, J., de Wit, S., Matulionyte, R., Law, M., Svedhem, V., Tallada, J., Garges, H. P., Marongiu, A., ... RESPOND Study Group (2024). Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 78(4), 995-1004. https://doi.org/10.1093/cid/ciad671

Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus. / Chammartin, Frédérique; Mocroft, Amanda; Egle, Alexander et al.
In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Vol. 78, No. 4, 10.04.2024, p. 995-1004.

Research output: Contribution to journal › Journal article › Research › peer-review

Chammartin, F, Mocroft, A, Egle, A, Zangerle, R, Smith, C, Mussini, C, Wit, F, Vehreschild, JJ, d'Arminio Monforte, A, Castagna, A, Bailly, L, Bogner, J, de Wit, S, Matulionyte, R, Law, M, Svedhem, V, Tallada, J, Garges, HP, Marongiu, A, Borges, ÁH , Jaschinski, N , Neesgaard, B , Ryom, L, Bucher, HC & RESPOND Study Group 2024, 'Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus', Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, vol. 78, no. 4, pp. 995-1004. https://doi.org/10.1093/cid/ciad671

Chammartin F, Mocroft A, Egle A, Zangerle R, Smith C, Mussini C et al. Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2024 Apr 10;78(4):995-1004. Epub 2023 Dec 13. doi: 10.1093/cid/ciad671

Chammartin, Frédérique ; Mocroft, Amanda ; Egle, Alexander et al. / Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus. In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2024 ; Vol. 78, No. 4. pp. 995-1004.

@article{b710d27b0b0d4cb9a00b1f2a5eb79750,

title = "Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus",

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.",

keywords = "Acquired Immunodeficiency Syndrome/complications, Anti-HIV Agents/adverse effects, Anti-Retroviral Agents/therapeutic use, CD4 Lymphocyte Count, CD4-CD8 Ratio, HIV, HIV Infections/complications, Humans, Neoplasms/complications, Viral Load, malignancy, antiretroviral therapy, CD4:CD8 ratio, observational study, HIV infection",

author = "Fr{\'e}d{\'e}rique Chammartin and Amanda Mocroft and Alexander Egle and Robert Zangerle and Colette Smith and Cristina Mussini and Ferdinand Wit and Vehreschild, \{J{\"o}rg Janne\} and \{d'Arminio Monforte\}, Antonella and Antonella Castagna and Laurent Bailly and Johannes Bogner and \{de Wit\}, St{\'e}phane and Raimonda Matulionyte and Matthew Law and Veronica Svedhem and Joan Tallada and Garges, \{Harmony P\} and Andrea Marongiu and Borges, \{{\'A}lvaro H\} and Nadine Jaschinski and Bastian Neesgaard and Lene Ryom and Bucher, \{Heiner C\} and \{RESPOND Study Group\}",

note = "{\textcopyright} The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.",

year = "2024",

month = apr,

day = "10",

doi = "10.1093/cid/ciad671",

language = "English",

volume = "78",

pages = "995--1004",

journal = "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "4",

}

TY - JOUR

T1 - Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus

AU - Chammartin, Frédérique

AU - Mocroft, Amanda

AU - Egle, Alexander

AU - Zangerle, Robert

AU - Smith, Colette

AU - Mussini, Cristina

AU - Wit, Ferdinand

AU - Vehreschild, Jörg Janne

AU - d'Arminio Monforte, Antonella

AU - Castagna, Antonella

AU - Bailly, Laurent

AU - Bogner, Johannes

AU - de Wit, Stéphane

AU - Matulionyte, Raimonda

AU - Law, Matthew

AU - Svedhem, Veronica

AU - Tallada, Joan

AU - Garges, Harmony P

AU - Marongiu, Andrea

AU - Borges, Álvaro H

AU - Jaschinski, Nadine

AU - Neesgaard, Bastian

AU - Ryom, Lene

AU - Bucher, Heiner C

AU - RESPOND Study Group

N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

PY - 2024/4/10

Y1 - 2024/4/10

N2 - 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.

AB - 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.

KW - Acquired Immunodeficiency Syndrome/complications

KW - Anti-HIV Agents/adverse effects

KW - Anti-Retroviral Agents/therapeutic use

KW - CD4 Lymphocyte Count

KW - CD4-CD8 Ratio

KW - HIV

KW - HIV Infections/complications

KW - Humans

KW - Neoplasms/complications

KW - Viral Load

KW - malignancy

KW - antiretroviral therapy

KW - CD4:CD8 ratio

KW - observational study

KW - HIV infection

UR - https://www.scopus.com/pages/publications/85190154853

U2 - 10.1093/cid/ciad671

DO - 10.1093/cid/ciad671

M3 - Journal article

C2 - 38092042

SN - 1058-4838

VL - 78

SP - 995

EP - 1004

JO - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

IS - 4

ER -

Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this