Relationship of immunologic response to antiretroviral therapy with non-AIDS defining cancer incidence.

Academic Article


  • OBJECTIVE: To estimate the association between immunologic response to antiretroviral therapy (ART) and non-AIDS defining cancer (NADC) incidence in HIV-infected patients. DESIGN: 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. CONCLUSION: 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.
  • Published In

  • AIDS  Journal
  • Keywords

  • Acquired Immunodeficiency Syndrome, Adolescent, Adult, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Cohort Studies, Female, Humans, Incidence, Male, Middle Aged, Neoplasms, Prospective Studies, RNA, Viral, United States, Young Adult
  • Digital Object Identifier (doi)

    Author List

  • Yanik EL; Napravnik S; Cole SR; Achenbach CJ; Gopal S; Dittmer DP; Olshan AF; Kitahata MM; Mugavero MJ; Saag M
  • Start Page

  • 979
  • End Page

  • 987
  • Volume

  • 28
  • Issue

  • 7