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
UR - http://www.scopus.com/inward/record.url?scp=85190154853&partnerID=8YFLogxK
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 -