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

Year: 2014
Type: article
Study design: Observational Study
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/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.
Source: AIDS
DOI: 10.1097/qad.0000000000000167
Authors: 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
Institutions: University of North Carolina at Chapel Hill, Johns Hopkins University, University of California, San Francisco, University of Alabama at Birmingham, Northwestern University, University of Washington, University of Alabama, University of California San Diego
Language: English
Subfield: Oncology
Field: Medicine
Open Access status: green
Funders: National Institutes of Health, National Institute on Drug Abuse, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Fogarty International Center, National Institute of Dental and Craniofacial Research
Awards: G1531094742, Johns Hopkins HIV Clinical Cohort, Developing a clinical cohort of histopathologically characterized lymphoma, G2127051194, G2516619799, G257334518, AIDS Malignancy Clinical Trials Consortium (AMC), G654751394, G683996958, Training in Sexually Transmitted Infections and HIV, STD and AIDS Research Training Grant, CFAR Network of Integrated Clinical Systems (CNICS), North American AIDS Cohorts on Collaboration and Design (NAACCORD), The University of North Carolina Center for AIDS Research, ART Modulation of Viral Pathogenesis, Cancer Center Support Grant
OpenAlex ID: W1964430278
FWCI: 1.436
Cites: 43
Cited by: 25
Related to: 10