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

Yanik, Elizabeth L.a; Napravnik, Soniaa; Cole, Stephen R.a; Achenbach, Chad J.b; Gopal, Satisha; Dittmer, Dirk P.a; Olshan, Andrew F.a; Kitahata, Mari M.c; Mugavero, Michael J.d; Saag, Michaeld; Moore, Richard D.e; Mathews, W. Christopherf; Hunt, Peterg; Eron, Joseph J.a

doi: 10.1097/QAD.0000000000000167
Clinical Science

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 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/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.

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.

Correspondence to Elizabeth L. Yanik, 9609 Medical Center Dr Rm. 6E-216, Rockville, MD 20850, USA. Tel: +1 240 276 7186; e-mail:

Received 5 October, 2013

Revised 27 November, 2013

Accepted 27 November, 2013

© 2014 Lippincott Williams & Wilkins, Inc.