Association of immunosuppression and HIV viraemia with non-Hodgkin lymphoma risk overall and by subtype in people living with HIV in Canada and the USA

a multicentre cohort study

North American AIDS Cohort Collaboration on Research and Design of the International Epidemiologic Databases to Evaluate AIDS

Research output: Contribution to journalArticle

Abstract

Background: Research is needed to better understand relations between immunosuppression and HIV viraemia and risk for non-Hodgkin lymphoma, a common cancer in people living with HIV. We aimed to identify key CD4 count and HIV RNA (viral load) predictors of risk for non-Hodgkin lymphoma, overall and by subtype. Methods: We studied people living with HIV during 1996–2014 from 21 Canadian and US cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. To determine key independent predictors of risk for non-Hodgkin lymphoma, we assessed associations with time-updated recent, past, cumulative, and nadir or peak measures of CD4 count and viral load, using demographics-adjusted, cohort-stratified Cox models, and we compared models using Akaike's information criterion. Findings: Of 102 131 people living with HIV during the study period, 712 people developed non-Hodgkin lymphoma. The key independent predictors of risk for overall non-Hodgkin lymphoma were recent CD4 count (ie, lagged by 6 months; <50 cells per μL vs ≥500 cells per μL, hazard ratio [HR] 3·2, 95% CI 2·2–4·7) and average viral load during a 3-year window lagged by 6 months (a cumulative measure; ≥100 000 copies per mL vs ≤500 copies per mL, HR 9·6, 95% CI 6·5–14·0). These measures were also the key predictors of risk for diffuse large B-cell lymphoma (recent CD4 count <50 cells per μL vs ≥500 cells per μL, HR 2·4, 95% CI 1·4–4·2; average viral load ≥100 000 copies per mL vs ≤500 copies per mL, HR 7·5, 95% CI 4·5–12·7). However, recent CD4 count was the sole key predictor of risk for CNS non-Hodgkin lymphoma (<50 cells per μL vs ≥500 cells per μL, HR 426·3, 95% CI 58·1–3126·4), and proportion of time viral load was greater than 500 copies per mL during the 3-year window (a cumulative measure) was the sole key predictor for Burkitt lymphoma (100% vs 0%, HR 41·1, 95% CI 9·1–186·6). Interpretation: Both recent immunosuppression and prolonged HIV viraemia have important independent roles in the development of non-Hodgkin lymphoma, with likely subtype heterogeneity. Early and sustained antiretroviral therapy to decrease HIV replication, dampen B-cell activation, and restore overall immune function is crucial for preventing non-Hodgkin lymphoma. Funding: National Institutes of Health, Centers for Disease Control and Prevention, US Agency for Healthcare Research and Quality, US Health Resources and Services Administration, Canadian Institutes of Health Research, Ontario Ministry of Health and Long Term Care, and the Government of Alberta.

Original languageEnglish (US)
Pages (from-to)e240-e249
JournalThe Lancet HIV
Volume6
Issue number4
DOIs
StatePublished - Apr 1 2019

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Viremia
Non-Hodgkin's Lymphoma
Immunosuppression
Multicenter Studies
Canada
Cohort Studies
HIV
CD4 Lymphocyte Count
Viral Load
United States Health Resources and Services Administration
United States Agency for Healthcare Research and Quality
Alberta
Burkitt Lymphoma
Lymphoma, Large B-Cell, Diffuse
Health
National Institutes of Health (U.S.)
Long-Term Care
Ontario
Centers for Disease Control and Prevention (U.S.)
Proportional Hazards Models

ASJC Scopus subject areas

  • Epidemiology
  • Immunology
  • Infectious Diseases
  • Virology

Cite this

Association of immunosuppression and HIV viraemia with non-Hodgkin lymphoma risk overall and by subtype in people living with HIV in Canada and the USA : a multicentre cohort study. / North American AIDS Cohort Collaboration on Research and Design of the International Epidemiologic Databases to Evaluate AIDS.

In: The Lancet HIV, Vol. 6, No. 4, 01.04.2019, p. e240-e249.

Research output: Contribution to journalArticle

North American AIDS Cohort Collaboration on Research and Design of the International Epidemiologic Databases to Evaluate AIDS 2019, 'Association of immunosuppression and HIV viraemia with non-Hodgkin lymphoma risk overall and by subtype in people living with HIV in Canada and the USA: a multicentre cohort study', The Lancet HIV, vol. 6, no. 4, pp. e240-e249. https://doi.org/10.1016/S2352-3018(18)30360-6
North American AIDS Cohort Collaboration on Research and Design of the International Epidemiologic Databases to Evaluate AIDS. / Association of immunosuppression and HIV viraemia with non-Hodgkin lymphoma risk overall and by subtype in people living with HIV in Canada and the USA : a multicentre cohort study. In: The Lancet HIV. 2019 ; Vol. 6, No. 4. pp. e240-e249.
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title = "Association of immunosuppression and HIV viraemia with non-Hodgkin lymphoma risk overall and by subtype in people living with HIV in Canada and the USA: a multicentre cohort study",
abstract = "Background: Research is needed to better understand relations between immunosuppression and HIV viraemia and risk for non-Hodgkin lymphoma, a common cancer in people living with HIV. We aimed to identify key CD4 count and HIV RNA (viral load) predictors of risk for non-Hodgkin lymphoma, overall and by subtype. Methods: We studied people living with HIV during 1996–2014 from 21 Canadian and US cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. To determine key independent predictors of risk for non-Hodgkin lymphoma, we assessed associations with time-updated recent, past, cumulative, and nadir or peak measures of CD4 count and viral load, using demographics-adjusted, cohort-stratified Cox models, and we compared models using Akaike's information criterion. Findings: Of 102 131 people living with HIV during the study period, 712 people developed non-Hodgkin lymphoma. The key independent predictors of risk for overall non-Hodgkin lymphoma were recent CD4 count (ie, lagged by 6 months; <50 cells per μL vs ≥500 cells per μL, hazard ratio [HR] 3·2, 95{\%} CI 2·2–4·7) and average viral load during a 3-year window lagged by 6 months (a cumulative measure; ≥100 000 copies per mL vs ≤500 copies per mL, HR 9·6, 95{\%} CI 6·5–14·0). These measures were also the key predictors of risk for diffuse large B-cell lymphoma (recent CD4 count <50 cells per μL vs ≥500 cells per μL, HR 2·4, 95{\%} CI 1·4–4·2; average viral load ≥100 000 copies per mL vs ≤500 copies per mL, HR 7·5, 95{\%} CI 4·5–12·7). However, recent CD4 count was the sole key predictor of risk for CNS non-Hodgkin lymphoma (<50 cells per μL vs ≥500 cells per μL, HR 426·3, 95{\%} CI 58·1–3126·4), and proportion of time viral load was greater than 500 copies per mL during the 3-year window (a cumulative measure) was the sole key predictor for Burkitt lymphoma (100{\%} vs 0{\%}, HR 41·1, 95{\%} CI 9·1–186·6). Interpretation: Both recent immunosuppression and prolonged HIV viraemia have important independent roles in the development of non-Hodgkin lymphoma, with likely subtype heterogeneity. Early and sustained antiretroviral therapy to decrease HIV replication, dampen B-cell activation, and restore overall immune function is crucial for preventing non-Hodgkin lymphoma. Funding: National Institutes of Health, Centers for Disease Control and Prevention, US Agency for Healthcare Research and Quality, US Health Resources and Services Administration, Canadian Institutes of Health Research, Ontario Ministry of Health and Long Term Care, and the Government of Alberta.",
author = "{North American AIDS Cohort Collaboration on Research and Design of the International Epidemiologic Databases to Evaluate AIDS} and Hern{\'a}ndez-Ram{\'i}rez, {Ra{\'u}l U.} and Li Qin and Haiqun Lin and Wendy Leyden and Neugebauer, {Romain S.} and Keri Althoff and Achenbach, {Chad J.} and Hessol, {Nancy A.} and Gypsyamber D'Souza and Kelly Gebo and Gill, {M. John} and Surbhi Grover and Horberg, {Michael A.} and Jun Li and Mathews, {W. Christopher} and Mayor, {Angel M.} and Park, {Lesley S.} and Rabkin, {Charles S.} and Kate Salters and Justice, {Amy C.} and Moore, {Richard D} and Engels, {Eric A.} and Silverberg, {Michael J.} and Robert Dubrow and Adrian Betts and Brooks, {John T.} and Freeman, {Aimee M.} and {Van Rompaey}, {Stephen E.} and Ann Burchell and Benita Yip and Bin You and Brenna Hogan and Chris Grasso and Hogg, {Robert S.} and Benson, {Constance A.} and Drozd, {Daniel R.} and Sterling, {Timothy R.} and David Haas and Elizabeth Humes and Crane, {Heidi M.} and James Willig and Eron, {Joseph J.} and Martin, {Jeffrey N.} and Saag, {Michael S.} and Jerry Jing and Jennifer Thorne and Jacobson, {Lisa Paula} and Gange, {Stephen J} and Kirk, {Gregory D} and Jennifer Lee",
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T1 - Association of immunosuppression and HIV viraemia with non-Hodgkin lymphoma risk overall and by subtype in people living with HIV in Canada and the USA

T2 - a multicentre cohort study

AU - North American AIDS Cohort Collaboration on Research and Design of the International Epidemiologic Databases to Evaluate AIDS

AU - Hernández-Ramírez, Raúl U.

AU - Qin, Li

AU - Lin, Haiqun

AU - Leyden, Wendy

AU - Neugebauer, Romain S.

AU - Althoff, Keri

AU - Achenbach, Chad J.

AU - Hessol, Nancy A.

AU - D'Souza, Gypsyamber

AU - Gebo, Kelly

AU - Gill, M. John

AU - Grover, Surbhi

AU - Horberg, Michael A.

AU - Li, Jun

AU - Mathews, W. Christopher

AU - Mayor, Angel M.

AU - Park, Lesley S.

AU - Rabkin, Charles S.

AU - Salters, Kate

AU - Justice, Amy C.

AU - Moore, Richard D

AU - Engels, Eric A.

AU - Silverberg, Michael J.

AU - Dubrow, Robert

AU - Betts, Adrian

AU - Brooks, John T.

AU - Freeman, Aimee M.

AU - Van Rompaey, Stephen E.

AU - Burchell, Ann

AU - Yip, Benita

AU - You, Bin

AU - Hogan, Brenna

AU - Grasso, Chris

AU - Hogg, Robert S.

AU - Benson, Constance A.

AU - Drozd, Daniel R.

AU - Sterling, Timothy R.

AU - Haas, David

AU - Humes, Elizabeth

AU - Crane, Heidi M.

AU - Willig, James

AU - Eron, Joseph J.

AU - Martin, Jeffrey N.

AU - Saag, Michael S.

AU - Jing, Jerry

AU - Thorne, Jennifer

AU - Jacobson, Lisa Paula

AU - Gange, Stephen J

AU - Kirk, Gregory D

AU - Lee, Jennifer

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Background: Research is needed to better understand relations between immunosuppression and HIV viraemia and risk for non-Hodgkin lymphoma, a common cancer in people living with HIV. We aimed to identify key CD4 count and HIV RNA (viral load) predictors of risk for non-Hodgkin lymphoma, overall and by subtype. Methods: We studied people living with HIV during 1996–2014 from 21 Canadian and US cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. To determine key independent predictors of risk for non-Hodgkin lymphoma, we assessed associations with time-updated recent, past, cumulative, and nadir or peak measures of CD4 count and viral load, using demographics-adjusted, cohort-stratified Cox models, and we compared models using Akaike's information criterion. Findings: Of 102 131 people living with HIV during the study period, 712 people developed non-Hodgkin lymphoma. The key independent predictors of risk for overall non-Hodgkin lymphoma were recent CD4 count (ie, lagged by 6 months; <50 cells per μL vs ≥500 cells per μL, hazard ratio [HR] 3·2, 95% CI 2·2–4·7) and average viral load during a 3-year window lagged by 6 months (a cumulative measure; ≥100 000 copies per mL vs ≤500 copies per mL, HR 9·6, 95% CI 6·5–14·0). These measures were also the key predictors of risk for diffuse large B-cell lymphoma (recent CD4 count <50 cells per μL vs ≥500 cells per μL, HR 2·4, 95% CI 1·4–4·2; average viral load ≥100 000 copies per mL vs ≤500 copies per mL, HR 7·5, 95% CI 4·5–12·7). However, recent CD4 count was the sole key predictor of risk for CNS non-Hodgkin lymphoma (<50 cells per μL vs ≥500 cells per μL, HR 426·3, 95% CI 58·1–3126·4), and proportion of time viral load was greater than 500 copies per mL during the 3-year window (a cumulative measure) was the sole key predictor for Burkitt lymphoma (100% vs 0%, HR 41·1, 95% CI 9·1–186·6). Interpretation: Both recent immunosuppression and prolonged HIV viraemia have important independent roles in the development of non-Hodgkin lymphoma, with likely subtype heterogeneity. Early and sustained antiretroviral therapy to decrease HIV replication, dampen B-cell activation, and restore overall immune function is crucial for preventing non-Hodgkin lymphoma. Funding: National Institutes of Health, Centers for Disease Control and Prevention, US Agency for Healthcare Research and Quality, US Health Resources and Services Administration, Canadian Institutes of Health Research, Ontario Ministry of Health and Long Term Care, and the Government of Alberta.

AB - Background: Research is needed to better understand relations between immunosuppression and HIV viraemia and risk for non-Hodgkin lymphoma, a common cancer in people living with HIV. We aimed to identify key CD4 count and HIV RNA (viral load) predictors of risk for non-Hodgkin lymphoma, overall and by subtype. Methods: We studied people living with HIV during 1996–2014 from 21 Canadian and US cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. To determine key independent predictors of risk for non-Hodgkin lymphoma, we assessed associations with time-updated recent, past, cumulative, and nadir or peak measures of CD4 count and viral load, using demographics-adjusted, cohort-stratified Cox models, and we compared models using Akaike's information criterion. Findings: Of 102 131 people living with HIV during the study period, 712 people developed non-Hodgkin lymphoma. The key independent predictors of risk for overall non-Hodgkin lymphoma were recent CD4 count (ie, lagged by 6 months; <50 cells per μL vs ≥500 cells per μL, hazard ratio [HR] 3·2, 95% CI 2·2–4·7) and average viral load during a 3-year window lagged by 6 months (a cumulative measure; ≥100 000 copies per mL vs ≤500 copies per mL, HR 9·6, 95% CI 6·5–14·0). These measures were also the key predictors of risk for diffuse large B-cell lymphoma (recent CD4 count <50 cells per μL vs ≥500 cells per μL, HR 2·4, 95% CI 1·4–4·2; average viral load ≥100 000 copies per mL vs ≤500 copies per mL, HR 7·5, 95% CI 4·5–12·7). However, recent CD4 count was the sole key predictor of risk for CNS non-Hodgkin lymphoma (<50 cells per μL vs ≥500 cells per μL, HR 426·3, 95% CI 58·1–3126·4), and proportion of time viral load was greater than 500 copies per mL during the 3-year window (a cumulative measure) was the sole key predictor for Burkitt lymphoma (100% vs 0%, HR 41·1, 95% CI 9·1–186·6). Interpretation: Both recent immunosuppression and prolonged HIV viraemia have important independent roles in the development of non-Hodgkin lymphoma, with likely subtype heterogeneity. Early and sustained antiretroviral therapy to decrease HIV replication, dampen B-cell activation, and restore overall immune function is crucial for preventing non-Hodgkin lymphoma. Funding: National Institutes of Health, Centers for Disease Control and Prevention, US Agency for Healthcare Research and Quality, US Health Resources and Services Administration, Canadian Institutes of Health Research, Ontario Ministry of Health and Long Term Care, and the Government of Alberta.

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JF - The Lancet HIV

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