title: Role of uncontrolled HIV RNA level and immunodeficiency in the occurrence of malignancy in HIV-infected patients during the combination antiretroviral therapy era: Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV)-infected patients are at higher risk of malignancies. In addition to traditional determinants, a specific deleterious effect of HIV and immunodeficiency is speculated. We aimed at studying the association between immunological and virological characteristics of HIV-infected patients in care and the risk of acquired immunodeficiency syndrome (AIDS)-defining and non-AIDS-defining malignancies.
  
  
  METHODS
  Patients consecutively enrolled in the hospital-based Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort were included if the duration of follow-up was >3 months during the period 1998-2006. Multivariate modeling used an extended Cox proportional hazards model for time-dependent covariates and delayed entry.
  
  
  RESULTS
  The 4194 patients included in the study developed 251 first malignancies during 22,389 person-years. A higher incidence of AIDS-defining malignancies (107 cases) was independently associated with (1) both longer and current exposures to a plasma HIV RNA level >500 copies/mL (hazard ratio [HR], 1.27 per year [P<.001] and 3.30 [P<.001], respectively) and (2) both longer and current exposure to a CD4(+) cell count <200 cells/mm(3) (HR, 1.36 per year [P<.001] and 6.33 [P<.001], respectively). A higher incidence of non-AIDS-defining malignancies (144 cases) was independently associated with longer and current exposure to a CD4(+) cell count <500 cells/mm(3) (HR, 1.13 per year [P=.01] and 2.07 [P<.001], respectively) and male sex (HR, 1.69; P=.02) but not with plasma HIV RNA level (P=.49 and P=.10 for cumulative and current exposures, respectively).
  
  
  CONCLUSIONS
  Uncontrolled plasma HIV RNA level was independently associated with a higher likelihood of developing AIDS-defining malignancies, whereas immunosuppression was associated with a higher risk of developing any type of malignancies. Antiretroviral treatment should aim at reaching and maintaining a CD4(+) count >500 cells/mm(3) to prevent the occurrence of malignancy, this should be integrated to malignancy-prevention policies.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U897.
authors.forename: Mathias
authors.initials: M
authors.lastname: Bruyand
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Thiébaut
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lawson-Ayayi
authors.forename: Pierre
authors.initials: P
authors.lastname: Joly
authors.forename: Annie Jeanne
authors.initials: AJ
authors.lastname: Sasco
authors.forename: Patrick
authors.initials: P
authors.lastname: Mercié
authors.forename: Jean Luc
authors.initials: JL
authors.lastname: Pellegrin
authors.forename: Didier
authors.initials: D
authors.lastname: Neau
authors.forename: François
authors.initials: F
authors.lastname: Dabis
authors.forename: Philippe
authors.initials: P
authors.lastname: Morlat
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chêne
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bonnet
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D009369:Neoplasms / Q000453:epidemiology*; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
chemical_list: D012367:RNA, Viral
references.citation: Curr Opin Oncol. 2007 Sep;19(5):446-51
references.pmid: 17762569
references.citation: AIDS. 2008 Oct 18;22(16):2135-41
references.pmid: 18832877
references.citation: Cancer. 2004 Jul 15;101(2):317-24
references.pmid: 15241829
references.citation: Clin Infect Dis. 2009 Mar 1;48(5):640-1
references.pmid: 19202628
references.citation: Int J Epidemiol. 2005 Feb;34(1):121-30
references.pmid: 15561752
references.citation: J Acquir Immune Defic Syndr. 2007 Sep 1;46(1):72-7
references.pmid: 17621240
references.citation: Am J Epidemiol. 1997 Oct 15;146(8):683-4
references.pmid: 9345125
references.citation: JAMA. 2006 Dec 20;296(23):2823-31
references.pmid: 17179459
references.citation: Int J Tuberc Lung Dis. 2006 Apr;10(4):378-83
references.pmid: 16602400
references.citation: AIDS. 2000 May 26;14(8):971-8
references.pmid: 10853978
references.citation: J Natl Cancer Inst. 1992 Oct 21;84(20):1593-5
references.pmid: 1404453
references.citation: Cancer. 2005 Oct 1;104(7):1505-11
references.pmid: 16104038
references.citation: Clin Infect Dis. 2006 Feb 1;42(3):411-7
references.pmid: 16392091
references.citation: Immunol Invest. 1997 Apr;26(3):351-70
references.pmid: 9129988
references.citation: Ann Intern Med. 2006 Sep 19;145(6):397-406
references.pmid: 16983127
references.citation: Eur J Cancer. 2007 Sep;43(14):2117-23
references.pmid: 17764927
references.citation: J Clin Oncol. 2003 Sep 15;21(18):3447-53
references.pmid: 12972519
references.citation: JAMA. 2001 Apr 4;285(13):1736-45
references.pmid: 11277828
references.citation: AIDS. 2003 May 23;17(8):1179-93
references.pmid: 12819520
references.citation: J Interferon Cytokine Res. 1995 Mar;15(3):261-8
references.pmid: 7584673
references.citation: Lancet. 2007 Jul 7;370(9581):59-67
references.pmid: 17617273
references.citation: Rev Epidemiol Sante Publique. 2003 Feb;51(1 Pt 1):3-30
references.pmid: 12684578
references.citation: AIDS. 2006 Aug 1;20(12):1645-54
references.pmid: 16868446
references.citation: J Acquir Immune Defic Syndr. 2008 Aug 15;48(5):590-8
references.pmid: 18645512
references.citation: IARC Sci Publ. 1987;(82):1-406
references.pmid: 3329634
references.citation: MMWR Recomm Rep. 1992 Dec 18;41(RR-17):1-19
references.pmid: 1361652
references.citation: Blood. 2004 Aug 15;104(4):942-7
references.pmid: 15117761
references.citation: Clin Infect Dis. 2009 Mar 1;48(5):633-9
references.pmid: 19202627
references.citation: AIDS. 2004 Nov 19;18(17):2285-93
references.pmid: 15577541
references.citation: Science. 1997 Mar 7;275(5305):1481-5
references.pmid: 9045614
references.citation: Science. 1994 Dec 16;266(5192):1865-9
references.pmid: 7997879
references.citation: J Natl Cancer Inst. 2005 Mar 16;97(6):425-32
references.pmid: 15770006
references.citation: HIV Med. 2007 Nov;8(8):547-54
references.pmid: 17944688