title: Relationship of immunologic response to antiretroviral therapy with non-AIDS defining cancer incidence.
abstract: OBJECTIVE
  To estimate the association between immunologic response to antiretroviral therapy (ART) and non-AIDS defining cancer (NADC) incidence in HIV-infected patients.
  
  
  METHODS
  A prospective cohort including patients with at least 1 cell/μl CD4 cell count and HIV-1 RNA measure after ART initiation between 1996 and 2011 in the Centers for AIDS Research Network of Integrated Clinical Systems, a collaboration of eight HIV clinics at major academic medical centres in the United States.
  
  
  METHODS
  Measures of immunologic response were 6-month CD4 post-ART, latest CD4 and CD4 count-years, a cumulative measure of CD4 lymphopenia. Cox regression with inverse probability-of-exposure weights was used to calculate adjusted hazard ratios of virus-related and virus-unrelated NADC incidence.
  
  
  RESULTS
  Among 9389 patients at ART initiation, median CD4 cell count was 200 cells/μl [interquartile range (IQR) 60-332)], and median HIV-1 RNA was 4.8 log10 copies/ml (IQR 4.3-5.4). Median follow-up was 3.3 years (IQR 1.5-6.5). After 6 months of ART, median CD4 cell count was 304 cells/μl (IQR 163-469). One hundred and sixty-four NADCs were diagnosed during study follow-up, 65 (40%) considered virus-related. Virus-related NADCs were inversely associated with 6-month CD4 cell count (hazard ratio per 100 cells/μl increase=0.71), latest CD4 cell count (hazard ratio per 100 cells/μl increase=0.70) and CD4 cell count-years (hazard ratio per 200 cell-years/μl increase=0.91) independent of CD4 cell count at ART initiation, age and HIV-1 RNA response. No associations were found with virus-unrelated NADCs.
  
  
  CONCLUSIONS
  Poor CD4 cell count response was strongly associated with virus-related NADC incidence, suggesting an important role for T-cell mediated immunity in pathogenesis. Lower CD4 cell count proximal to cancer diagnosis may be a result of subclinical cancer. Intensified cancer screening should be considered for patients on ART with low CD4 cell counts.
authors.affiliation: aUniversity of North Carolina, Chapel Hill, North Carolina bNorthwestern University, Chicago, Illinois cUniversity of Washington, Seattle, Washington dUniversity of Alabama, Birmingham, Alabama eJohns Hopkins University, Baltimore, Maryland fUniversity of California, San Diego gUniversity of California, San Francisco, California, USA.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Yanik
authors.forename: Sonia
authors.initials: S
authors.lastname: Napravnik
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Cole
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Achenbach
authors.forename: Satish
authors.initials: S
authors.lastname: Gopal
authors.forename: Dirk P
authors.initials: DP
authors.lastname: Dittmer
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Olshan
authors.forename: Mari M
authors.initials: MM
authors.lastname: Kitahata
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mugavero
authors.forename: Michael
authors.initials: M
authors.lastname: Saag
authors.forename: Richard D
authors.initials: RD
authors.lastname: Moore
authors.forename: W Christopher
authors.initials: WC
authors.lastname: Mathews
authors.forename: Peter
authors.initials: P
authors.lastname: Hunt
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology*; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral