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

Elizabeth L. Yanik, Sonia Napravnik, Stephen R. Cole, Chad J. Achenbach, Satish Gopal, Dirk P. Dittmer, Andrew F. Olshan, Mari M. Kitahata, Michael J. Mugavero, Michael Saag, Richard D Moore, W. Christopher Mathews, Peter Hunt, Joseph J. Eron

Research output: Contribution to journalArticle

Abstract

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/ml 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/ml [interquartile range (IQR) 60-332)], and median HIV-1 RNA was 4.8 log10copies/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/ml (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/ml increase1/40.71), latest CD4+ cell count (hazard ratio per 100 cells/ml increase1/40.70) and CD4+ cell count-years (hazard ratio per 200 cellyears/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.

Original languageEnglish (US)
Pages (from-to)979-987
Number of pages9
JournalAIDS
Volume28
Issue number7
DOIs
StatePublished - Apr 24 2014

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CD4 Lymphocyte Count
Incidence
Neoplasms
Viruses
Therapeutics
HIV-1
RNA
HIV
Satellite Viruses
Lymphopenia
Early Detection of Cancer
Cellular Immunity
Acquired Immunodeficiency Syndrome
T-Lymphocytes
Weights and Measures

Keywords

  • antiretroviral therapy
  • cancers
  • HIV infections,immune reconstitution
  • tumour virus infections

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Yanik, E. L., Napravnik, S., Cole, S. R., Achenbach, C. J., Gopal, S., Dittmer, D. P., ... Eron, J. J. (2014). Relationship of immunologic response to antiretroviral therapy with non-AIDS defining cancer incidence. AIDS, 28(7), 979-987. https://doi.org/10.1097/QAD.0000000000000167

Relationship of immunologic response to antiretroviral therapy with non-AIDS defining cancer incidence. / Yanik, Elizabeth L.; Napravnik, Sonia; Cole, Stephen R.; Achenbach, Chad J.; Gopal, Satish; Dittmer, Dirk P.; Olshan, Andrew F.; Kitahata, Mari M.; Mugavero, Michael J.; Saag, Michael; Moore, Richard D; Mathews, W. Christopher; Hunt, Peter; Eron, Joseph J.

In: AIDS, Vol. 28, No. 7, 24.04.2014, p. 979-987.

Research output: Contribution to journalArticle

Yanik, EL, Napravnik, S, Cole, SR, Achenbach, CJ, Gopal, S, Dittmer, DP, Olshan, AF, Kitahata, MM, Mugavero, MJ, Saag, M, Moore, RD, Mathews, WC, Hunt, P & Eron, JJ 2014, 'Relationship of immunologic response to antiretroviral therapy with non-AIDS defining cancer incidence', AIDS, vol. 28, no. 7, pp. 979-987. https://doi.org/10.1097/QAD.0000000000000167
Yanik EL, Napravnik S, Cole SR, Achenbach CJ, Gopal S, Dittmer DP et al. Relationship of immunologic response to antiretroviral therapy with non-AIDS defining cancer incidence. AIDS. 2014 Apr 24;28(7):979-987. https://doi.org/10.1097/QAD.0000000000000167
Yanik, Elizabeth L. ; Napravnik, Sonia ; Cole, Stephen R. ; Achenbach, Chad J. ; Gopal, Satish ; Dittmer, Dirk P. ; Olshan, Andrew F. ; Kitahata, Mari M. ; Mugavero, Michael J. ; Saag, Michael ; Moore, Richard D ; Mathews, W. Christopher ; Hunt, Peter ; Eron, Joseph J. / Relationship of immunologic response to antiretroviral therapy with non-AIDS defining cancer incidence. In: AIDS. 2014 ; Vol. 28, No. 7. pp. 979-987.
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abstract = "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/ml 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/ml [interquartile range (IQR) 60-332)], and median HIV-1 RNA was 4.8 log10copies/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/ml (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/ml increase1/40.71), latest CD4+ cell count (hazard ratio per 100 cells/ml increase1/40.70) and CD4+ cell count-years (hazard ratio per 200 cellyears/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.",
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AU - Yanik, Elizabeth L.

AU - Napravnik, Sonia

AU - Cole, Stephen R.

AU - Achenbach, Chad J.

AU - Gopal, Satish

AU - Dittmer, Dirk P.

AU - Olshan, Andrew F.

AU - Kitahata, Mari M.

AU - Mugavero, Michael J.

AU - Saag, Michael

AU - Moore, Richard D

AU - Mathews, W. Christopher

AU - Hunt, Peter

AU - Eron, Joseph J.

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N2 - 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/ml 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/ml [interquartile range (IQR) 60-332)], and median HIV-1 RNA was 4.8 log10copies/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/ml (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/ml increase1/40.71), latest CD4+ cell count (hazard ratio per 100 cells/ml increase1/40.70) and CD4+ cell count-years (hazard ratio per 200 cellyears/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.

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