Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia With Anal Cancer Risk in Persons Living With HIV in the United States and Canada
Authors: Hernández-Ramírez Raúl U , Qin Li , Lin Haiqun , Leyden Wendy , Neugebauer Romain S , Althoff Keri N , Hessol Nancy A , Achenbach Chad J , Brooks John T , Gill M John , Grover Surbhi , Horberg Michael A , Li Jun , Mathews W Christopher , Mayor Angel M , Patel Pragna , Rabkin Charles S , Rachlis Anita , Justice Amy C , Moore Richard D , Engels Eric A , Silverberg Michael J , Dubrow Robert ,   North American AIDS Cohort Collaboration on Research and Design of the International Epidemiologic Databases to Evaluate AIDS, Benson Constance A , Bosch Ronald J , Kirk Gregory D , Mayer Kenneth H , Grasso Chris , Hogg Robert S , Richard Harrigan P , Montaner Julio S G , Yip Benita , Zhu Julia , Salters Kate , Gabler Karyn , Buchacz Kate , Li Jun , Gebo Kelly A , Moore Richard D , Moore Richard D , Rodriguez Benigno , Horberg Michael A , Silverberg Michael J , Thorne Jennifer E , Rabkin Charles , Margolick Joseph B , Jacobson Lisa P , D’Souza Gypsyamber , Klein Marina B , Kroch Abigail , Burchell Ann , Betts Adrian , Lindsay Joanne , Hunter-Mellado Robert F , Mayor Angel M , John Gill M , Deeks Steven G , Martin Jeffrey N , Li Jun , Brooks John T , Saag Michael S , Mugavero Michael J , Willig James , Mathews William C , Eron Joseph J , Napravnik Sonia , Kitahata Mari M , Crane Heidi M , Drozd Daniel R , Sterling Timothy R , Haas David , Rebeiro Peter , Turner Megan , Justice Amy C , Dubrow Robert , Fiellin David , Gange Stephen J , Anastos Kathryn , Moore Richard D , Saag Michael S , Gange Stephen J , Kitahata Mari M , Althoff Keri N , Horberg Michael A , Klein Marina B , McKaig Rosemary G , Freeman Aimee M , Moore Richard D , Freeman Aimee M , Kitahata Mari M , Van Rompaey Stephen E , Crane Heidi M , Drozd Daniel R , Morton Liz , McReynolds Justin , Lober William B , Gange Stephen J , Althoff Keri N , Lee Jennifer S , You Bin , Hogan Brenna , Zhang Jinbing , Jing Jerry , Humes Elizabeth , Coburn Sally 
Published: April 2019

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 &lt;50 vs ≥500 cells/µL, 13.4; 95% confidence interval [CI], 3.5–51.0) and proportion of time CD4 &lt;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.