Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia With Anal Cancer Risk in Persons Living With HIV in the United States and Canada.
CD4+ T-cell count
HIV infection
HIV-1 RNA viral load
anal cancer
risk
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
03 03 2020
03 03 2020
Historique:
received:
07
01
2019
accepted:
22
04
2019
pubmed:
3
5
2019
medline:
7
1
2021
entrez:
3
5
2019
Statut:
ppublish
Résumé
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. 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. 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 31044245
pii: 5482475
doi: 10.1093/cid/ciz329
pmc: PMC7319056
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1176-1185Subventions
Organisme : CIHR
ID : TGF-96118
Pays : Canada
Organisme : NIAID NIH HHS
ID : P30 AI094189
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : CIHR
ID : CBR-94036
Pays : Canada
Organisme : NIMHD NIH HHS
ID : U54 MD007587
Pays : United States
Organisme : CIHR
ID : HCP-97105
Pays : Canada
Organisme : NIAID NIH HHS
ID : P30 AI027757
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI050410
Pays : United States
Organisme : CIHR
ID : CBR-86906
Pays : Canada
Organisme : NCI NIH HHS
ID : K08 CA230170
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI027763
Pays : United States
Investigateurs
Constance A Benson
(CA)
Ronald J Bosch
(RJ)
Gregory D Kirk
(GD)
Kenneth H Mayer
(KH)
Chris Grasso
(C)
Robert S Hogg
(RS)
P Richard Harrigan
(P)
Julio S G Montaner
(JSG)
Benita Yip
(B)
Julia Zhu
(J)
Kate Salters
(K)
Karyn Gabler
(K)
Kate Buchacz
(K)
Jun Li
(J)
Kelly A Gebo
(KA)
Richard D Moore
(RD)
Richard D Moore
(RD)
Benigno Rodriguez
(B)
Michael A Horberg
(MA)
Michael J Silverberg
(MJ)
Jennifer E Thorne
(JE)
Charles Rabkin
(C)
Joseph B Margolick
(JB)
Lisa P Jacobson
(LP)
Gypsyamber D'Souza
(G)
Marina B Klein
(MB)
Abigail Kroch
(A)
Ann Burchell
(A)
Adrian Betts
(A)
Joanne Lindsay
(J)
Robert F Hunter-Mellado
(RF)
Angel M Mayor
(AM)
M John Gill
(M)
Steven G Deeks
(SG)
Jeffrey N Martin
(JN)
Jun Li
(J)
John T Brooks
(JT)
Michael S Saag
(MS)
Michael J Mugavero
(MJ)
James Willig
(J)
William C Mathews
(WC)
Joseph J Eron
(JJ)
Sonia Napravnik
(S)
Mari M Kitahata
(MM)
Heidi M Crane
(HM)
Daniel R Drozd
(DR)
Timothy R Sterling
(TR)
David Haas
(D)
Peter Rebeiro
(P)
Megan Turner
(M)
Amy C Justice
(AC)
Robert Dubrow
(R)
David Fiellin
(D)
Stephen J Gange
(SJ)
Kathryn Anastos
(K)
Richard D Moore
(RD)
Michael S Saag
(MS)
Stephen J Gange
(SJ)
Mari M Kitahata
(MM)
Keri N Althoff
(KN)
Michael A Horberg
(MA)
Marina B Klein
(MB)
Rosemary G McKaig
(RG)
Aimee M Freeman
(AM)
Richard D Moore
(RD)
Aimee M Freeman
(AM)
Mari M Kitahata
(MM)
Stephen E Van Rompaey
(SE)
Heidi M Crane
(HM)
Daniel R Drozd
(DR)
Liz Morton
(L)
Justin McReynolds
(J)
William B Lober
(WB)
Stephen J Gange
(SJ)
Keri N Althoff
(KN)
Jennifer S Lee
(JS)
Bin You
(B)
Brenna Hogan
(B)
Jinbing Zhang
(J)
Jerry Jing
(J)
Elizabeth Humes
(E)
Sally Coburn
(S)
Informations de copyright
© 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.
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