@article{85eaea953eb84e1bbc114592a8d057ea,
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 {John Gill}, M. 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 = "Funding Information: Financial support. This work was supported by the NIH (grant numbers U01AI069918, F31AI124794, F31DA037788, G12MD007583, K01AI093197, K01AI131895, K23EY013707, K24AI065298, K24AI118591, K24DA000432, KL2TR000421, M01RR000052, N01CP001004, N02CP055504, N02CP91027, P30AI027757, P30AI027763, P30AI027767, P30AI036219, P30AI050410, P30AI094189, P30AI110527, P30MH62246, R01AA016893, R01CA165937, R01DA011602, R01DA012568, R01AG053100, R24AI067039, U01AA013566, U01AA020790, U01AI031834, U01AI034989, U01AI034993, U01AI034994, U01AI035004, U01AI035039, U01AI035040, U01AI035041, U01AI035042, U01AI037613, U01AI037984, U01AI038855, U01AI038858, U01AI042590, U01AI068634, U01AI068636, U01AI069432, U01AI069434, U01AI103390, U01AI103397, U01AI103401, U01AI103408, U01DA03629, U01DA036935, U01HD032632, U10EY008057, U10EY008052, U10EY008067, U24AA020794, U54MD007587, UL1RR024131, UL1TR000004, UL1TR000083, UL1TR000454, UM1AI035043, Z01CP010214, and Z01CP010176); the CDC (contracts CDC-200-2006-18797 and CDC-200-2015-63931); the Agency for Healthcare Research and Quality (US; contract 90047713); the Health Resources and Services Administration (US; contract 90051652); the Canadian Institutes of Health Research (grant numbers CBR-86906, CBR-94036, HCP-97105, and TGF-96118); the Ontario Ministry of Health and Long Term Care; and the Government of Alberta. Additional support was provided by the National Cancer Institute, National Institute for Mental Health, and National Institute on Drug Abuse. Funding Information: Potential conflicts of interest. K. N. A. serves on the scientific advisory board of TrioHealth, Inc. M. J. G. has served as an ad hoc member of Canadian HIV Advisory Boards of Merck, Gilead, and ViiV. A. R. has provided clinical research support to Merck Frosst, ViiV Healthcare, Gilead Sciences, and Janssen. R. D. M. has previously consulted for Medscape. M. J. S. has received grants from Gilead and, formerly, Merck. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. 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",
}