Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia with Anal Cancer Risk in Persons Living with HIV in the United States and Canada

Raúl U. Hernández-Ramírez; Li Qin; Haiqun Lin; Wendy Leyden; Romain S. Neugebauer; Keri N. Althoff; Nancy A. Hessol; Chad J. Achenbach; John T. Brooks; M. John Gill; Surbhi Grover; Michael A. Horberg; Jun Li; W. Christopher Mathews; Angel M. Mayor; Pragna Patel; Charles S. Rabkin; Anita Rachlis; Amy C. Justice; Richard D. Moore; Eric A. Engels; Michael J. Silverberg; Robert Dubrow; Constance A. Benson; Ronald J. Bosch; Gregory D. Kirk; Kenneth H. Mayer; Chris Grasso; Robert S. Hogg; P. Richard Harrigan; Julio S.G. Montaner; Benita Yip; Julia Zhu; Kate Salters; Karyn Gabler; Kate Buchacz; Kelly A. Gebo; Benigno Rodriguez; Jennifer E. Thorne; Joseph B. Margolick; Lisa P. Jacobson; Gypsyamber D'Souza; Marina B. Klein; Abigail Kroch; Ann Burchell; Adrian Betts; Joanne Lindsay; Robert F. Hunter-Mellado; Steven G. Deeks; Jeffrey N. Martin; Michael S. Saag; Michael J. Mugavero; James Willig; William C. Mathews; Joseph J. Eron; Sonia Napravnik; Mari M. Kitahata; Heidi M. Crane; Daniel R. Drozd; Timothy R. Sterling; David Haas; Peter Rebeiro; Megan Turner; David Fiellin; Stephen J. Gange; Kathryn Anastos; Rosemary G. McKaig; Aimee M. Freeman; Stephen E. Van Rompaey; Liz Morton; Justin McReynolds; William B. Lober; Jennifer S. Lee; Bin You; Brenna Hogan; Jinbing Zhang; Jerry Jing; Elizabeth Humes; Sally Coburn

doi:10.1093/cid/ciz329

Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia with Anal Cancer Risk in Persons Living with HIV in the United States and Canada

Raúl U. Hernández-Ramírez, Li Qin, Haiqun Lin, Wendy Leyden, Romain S. Neugebauer, Keri N. Althoff, Nancy A. Hessol, Chad J. Achenbach, John T. Brooks, M. John Gill, Surbhi Grover, Michael A. Horberg, Jun Li, W. Christopher Mathews, Angel M. Mayor, Pragna Patel, Charles S. Rabkin, Anita Rachlis, Amy C. Justice, Richard D. MooreEric A. Engels, Michael J. Silverberg, Robert Dubrow, Constance A. Benson, Ronald J. Bosch, Gregory D. Kirk, Kenneth H. Mayer, Chris Grasso, Robert S. Hogg, P. Richard Harrigan, Julio S.G. Montaner, Benita Yip, Julia Zhu, Kate Salters, Karyn Gabler, Kate Buchacz, Kelly A. Gebo, Benigno Rodriguez, Jennifer E. Thorne, Joseph B. Margolick, Lisa P. Jacobson, Gypsyamber D'Souza, Marina B. Klein, Abigail Kroch, Ann Burchell, Adrian Betts, Joanne Lindsay, Robert F. Hunter-Mellado, Steven G. Deeks, Jeffrey N. Martin, Michael S. Saag, Michael J. Mugavero, James Willig, William C. Mathews, Joseph J. Eron, Sonia Napravnik, Mari M. Kitahata, Heidi M. Crane, Daniel R. Drozd, Timothy R. Sterling, David Haas, Peter Rebeiro, Megan Turner, David Fiellin, Stephen J. Gange, Kathryn Anastos, Rosemary G. McKaig, Aimee M. Freeman, Stephen E. Van Rompaey, Liz Morton, Justin McReynolds, William B. Lober, Jennifer S. Lee, Bin You, Brenna Hogan, Jinbing Zhang, Jerry Jing, Elizabeth Humes, Sally Coburn

Medicine

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

Background: People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk. Methods: We studied 102 777 PLWH during 1996-2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion. Results: Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for <50 vs ≥500 cells/μL, 13.4; 95% confidence interval [CI], 3.5-51.0) and proportion of time CD4 <200 cells/μL from approximately 8.5 to 4.5 years in the past (a cumulative measure; HR for 100% vs 0%, 3.1; 95% CI, 1.5-6.6). Conclusions: Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk.

Original language	English (US)
Pages (from-to)	1176-1185
Number of pages	10
Journal	Clinical Infectious Diseases
Volume	70
Issue number	6
DOIs	https://doi.org/10.1093/cid/ciz329
State	Published - Mar 3 2020

Keywords

CD4+ T-cell count
HIV infection
HIV-1 RNA viral load
anal cancer
risk

ASJC Scopus subject areas

Microbiology (medical)
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/cid/ciz329

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Hernández-Ramírez, R. U., Qin, L., Lin, H., Leyden, W., Neugebauer, R. S., Althoff, K. N., Hessol, N. A., Achenbach, C. J., Brooks, J. T., Gill, M. J., Grover, S., Horberg, M. A., Li, J., Mathews, W. C., Mayor, A. M., Patel, P., Rabkin, C. S., Rachlis, A., Justice, A. C., ... Coburn, S. (2020). Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia with Anal Cancer Risk in Persons Living with HIV in the United States and Canada. Clinical Infectious Diseases, 70(6), 1176-1185. https://doi.org/10.1093/cid/ciz329

Hernández-Ramírez, RU, Qin, L, Lin, H, Leyden, W, Neugebauer, RS, Althoff, KN, Hessol, NA, Achenbach, CJ, Brooks, JT, Gill, MJ, Grover, S, Horberg, MA, Li, J, Mathews, WC, Mayor, AM, Patel, P, Rabkin, CS, Rachlis, A, Justice, AC, Moore, RD, Engels, EA, Silverberg, MJ, Dubrow, R, Benson, CA, Bosch, RJ, Kirk, GD, Mayer, KH, Grasso, C, Hogg, RS, Richard Harrigan, P, Montaner, JSG, Yip, B, Zhu, J, Salters, K, Gabler, K, Buchacz, K, Gebo, KA, Rodriguez, B, Thorne, JE, Margolick, JB, Jacobson, LP, D'Souza, G, Klein, MB, Kroch, A, Burchell, A, Betts, A, Lindsay, J, Hunter-Mellado, RF, Deeks, SG, Martin, JN, Saag, MS, Mugavero, MJ, Willig, J, Mathews, WC, Eron, JJ, Napravnik, S, Kitahata, MM, Crane, HM, Drozd, DR, Sterling, TR, Haas, D, Rebeiro, P, Turner, M, Fiellin, D, Gange, SJ, Anastos, K, McKaig, RG, Freeman, AM, Van Rompaey, SE, Morton, L, McReynolds, J, Lober, WB, Lee, JS, You, B, Hogan, B, Zhang, J, Jing, J, Humes, E & Coburn, S 2020, 'Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia with Anal Cancer Risk in Persons Living with HIV in the United States and Canada', Clinical Infectious Diseases, vol. 70, no. 6, pp. 1176-1185. https://doi.org/10.1093/cid/ciz329

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title = "Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia with Anal Cancer Risk in Persons Living with HIV in the United States and Canada",

abstract = "Background: People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk. Methods: We studied 102 777 PLWH during 1996-2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion. Results: Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for <50 vs ≥500 cells/μL, 13.4; 95% confidence interval [CI], 3.5-51.0) and proportion of time CD4 <200 cells/μL from approximately 8.5 to 4.5 years in the past (a cumulative measure; HR for 100% vs 0%, 3.1; 95% CI, 1.5-6.6). Conclusions: Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk.",

keywords = "CD4+ T-cell count, HIV infection, HIV-1 RNA viral load, anal cancer, risk",

author = "Hern{\'a}ndez-Ram{\'i}rez, {Ra{\'u}l U.} and Li Qin and Haiqun Lin and Wendy Leyden and Neugebauer, {Romain S.} and Althoff, {Keri N.} and Hessol, {Nancy A.} and Achenbach, {Chad J.} and Brooks, {John T.} and Gill, {M. John} and Surbhi Grover and Horberg, {Michael A.} and Jun Li and Mathews, {W. Christopher} and Mayor, {Angel M.} and Pragna Patel and Rabkin, {Charles S.} and Anita Rachlis and Justice, {Amy C.} and Moore, {Richard D.} and Engels, {Eric A.} and Silverberg, {Michael J.} and Robert Dubrow and Benson, {Constance A.} and Bosch, {Ronald J.} and Kirk, {Gregory D.} and Mayer, {Kenneth H.} and Chris Grasso and Hogg, {Robert S.} and {Richard Harrigan}, P. and Montaner, {Julio S.G.} and Benita Yip and Julia Zhu and Kate Salters and Karyn Gabler and Kate Buchacz and Gebo, {Kelly A.} and Benigno Rodriguez and Thorne, {Jennifer E.} and Margolick, {Joseph B.} and Jacobson, {Lisa P.} and Gypsyamber D'Souza and Klein, {Marina B.} and Abigail Kroch and Ann Burchell and Adrian Betts and Joanne Lindsay and Hunter-Mellado, {Robert F.} and Deeks, {Steven G.} and Martin, {Jeffrey N.} and Saag, {Michael S.} and Mugavero, {Michael J.} and James Willig and Mathews, {William C.} and Eron, {Joseph J.} and Sonia Napravnik and Kitahata, {Mari M.} and Crane, {Heidi M.} and Drozd, {Daniel R.} and Sterling, {Timothy R.} and David Haas and Peter Rebeiro and Megan Turner and David Fiellin and Gange, {Stephen J.} and Kathryn Anastos and McKaig, {Rosemary G.} and Freeman, {Aimee M.} and {Van Rompaey}, {Stephen E.} and Liz Morton and Justin McReynolds and Lober, {William B.} and Lee, {Jennifer S.} and Bin You and Brenna Hogan and Jinbing Zhang and Jerry Jing and Elizabeth Humes and Sally Coburn",

note = "Publisher Copyright: {\textcopyright} 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.",

year = "2020",

month = mar,

day = "3",

doi = "10.1093/cid/ciz329",

language = "English (US)",

volume = "70",

pages = "1176--1185",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "6",

}

TY - JOUR

T1 - Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia with Anal Cancer Risk in Persons Living with HIV in the United States and Canada

AU - Hernández-Ramírez, Raúl U.

AU - Qin, Li

AU - Lin, Haiqun

AU - Leyden, Wendy

AU - Neugebauer, Romain S.

AU - Althoff, Keri N.

AU - Hessol, Nancy A.

AU - Achenbach, Chad J.

AU - Brooks, John T.

AU - Gill, M. John

AU - Grover, Surbhi

AU - Horberg, Michael A.

AU - Li, Jun

AU - Mathews, W. Christopher

AU - Mayor, Angel M.

AU - Patel, Pragna

AU - Rabkin, Charles S.

AU - Rachlis, Anita

AU - Justice, Amy C.

AU - Moore, Richard D.

AU - Engels, Eric A.

AU - Silverberg, Michael J.

AU - Dubrow, Robert

AU - Benson, Constance A.

AU - Bosch, Ronald J.

AU - Kirk, Gregory D.

AU - Mayer, Kenneth H.

AU - Grasso, Chris

AU - Hogg, Robert S.

AU - Richard Harrigan, P.

AU - Montaner, Julio S.G.

AU - Yip, Benita

AU - Zhu, Julia

AU - Salters, Kate

AU - Gabler, Karyn

AU - Buchacz, Kate

AU - Gebo, Kelly A.

AU - Rodriguez, Benigno

AU - Thorne, Jennifer E.

AU - Margolick, Joseph B.

AU - Jacobson, Lisa P.

AU - D'Souza, Gypsyamber

AU - Klein, Marina B.

AU - Kroch, Abigail

AU - Burchell, Ann

AU - Betts, Adrian

AU - Lindsay, Joanne

AU - Hunter-Mellado, Robert F.

AU - Deeks, Steven G.

AU - Martin, Jeffrey N.

AU - Saag, Michael S.

AU - Mugavero, Michael J.

AU - Willig, James

AU - Mathews, William C.

AU - Eron, Joseph J.

AU - Napravnik, Sonia

AU - Kitahata, Mari M.

AU - Crane, Heidi M.

AU - Drozd, Daniel R.

AU - Sterling, Timothy R.

AU - Haas, David

AU - Rebeiro, Peter

AU - Turner, Megan

AU - Fiellin, David

AU - Gange, Stephen J.

AU - Anastos, Kathryn

AU - McKaig, Rosemary G.

AU - Freeman, Aimee M.

AU - Van Rompaey, Stephen E.

AU - Morton, Liz

AU - McReynolds, Justin

AU - Lober, William B.

AU - Lee, Jennifer S.

AU - You, Bin

AU - Hogan, Brenna

AU - Zhang, Jinbing

AU - Jing, Jerry

AU - Humes, Elizabeth

AU - Coburn, Sally

N1 - Publisher Copyright: © 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

PY - 2020/3/3

Y1 - 2020/3/3

N2 - Background: People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk. Methods: We studied 102 777 PLWH during 1996-2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion. Results: Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for <50 vs ≥500 cells/μL, 13.4; 95% confidence interval [CI], 3.5-51.0) and proportion of time CD4 <200 cells/μL from approximately 8.5 to 4.5 years in the past (a cumulative measure; HR for 100% vs 0%, 3.1; 95% CI, 1.5-6.6). Conclusions: Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk.

AB - Background: People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk. Methods: We studied 102 777 PLWH during 1996-2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion. Results: Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for <50 vs ≥500 cells/μL, 13.4; 95% confidence interval [CI], 3.5-51.0) and proportion of time CD4 <200 cells/μL from approximately 8.5 to 4.5 years in the past (a cumulative measure; HR for 100% vs 0%, 3.1; 95% CI, 1.5-6.6). Conclusions: Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk.

KW - CD4+ T-cell count

KW - HIV infection

KW - HIV-1 RNA viral load

KW - anal cancer

KW - risk

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U2 - 10.1093/cid/ciz329

DO - 10.1093/cid/ciz329

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AN - SCOPUS:85081126906

SN - 1058-4838

VL - 70

SP - 1176

EP - 1185

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 6

ER -

Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia with Anal Cancer Risk in Persons Living with HIV in the United States and Canada

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Keywords

ASJC Scopus subject areas

UN SDGs

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