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Serological Assessment of 18 Pathogens and Risk of AIDS-Associated Non-Hodgkin Lymphoma

Halec, Gordana PhD*; Waterboer, Tim PhD; Brenner, Nicole MSc; Butt, Julia PhD; Hardy, W. David MD; D'Souza, Gypsyamber PhD§; Wolinsky, Steven MD; Macatangay, Bernard J. MD; Pawlita, Michael MD; Detels, Roger MD#; Martínez-Maza, Otoniel PhD*; Hussain, Shehnaz K. PhD#,**

JAIDS Journal of Acquired Immune Deficiency Syndromes: March 1, 2019 - Volume 80 - Issue 3 - p e53–e63
doi: 10.1097/QAI.0000000000001916

Background: HIV infection is associated with increased susceptibility to common pathogens, which may trigger chronic antigenic stimulation and hyperactivation of B cells, events known to precede the development of AIDS-associated non-Hodgkin lymphoma (AIDS-NHL).

Methods: To explore whether cumulative exposure to infectious agents contributes to AIDS-NHL risk, we tested sera from 199 AIDS-NHL patients (pre-NHL, average lead time 3.9 years) and 199 matched HIV-infected controls from the Multicenter AIDS Cohort Study, for anti-IgG responses to 18 pathogens using multiplex serology. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression models.

Results: We found no association between cumulative exposure to infectious agents and AIDS-NHL risk (OR 1.01, 95% CI: 0.91 to 1.12). However, seropositivity for trichodysplasia spinulosa polyomavirus (TSPyV), defined as presence of antibodies to TSPyV capsid protein VP1, was significantly associated with a 1.6-fold increase in AIDS-NHL risk (OR 1.62, 95% CI: 1.02 to 2.57). High Epstein–Barr virus (EBV) anti-VCA p18 antibody levels closer to the time of AIDS-NHL diagnosis (<4 years) were associated with a 2.6-fold increase in AIDS-NHL risk (OR 2.59, 95% CI: 1.17 to 5.74). In addition, high EBV anti-EBNA-1 and anti-ZEBRA antibody levels were associated with 2.1-fold (OR 0.47, 95% CI: 0.26 to 0.85) and 1.6-fold (OR 0.57, 95% CI: 0.35 to 0.93) decreased risk of AIDS-NHL, respectively.

Conclusions: Our results do not support the hypothesis that cumulative exposure to infectious agents contributes to AIDS-NHL development. However, the observed associations with respect to TSPyV seropositivity and EBV antigen antibody levels offer additional insights into the pathogenesis of AIDS-NHL.

*Department of Obstetrics and Gynecology, AIDS Institute, UCLA David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA;

Infections and Cancer Epidemiology, Research Program Infection, Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany;

Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD;

§Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;

Division of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL;

Division of Infectious Diseases, Department of Medicine, University of Pittsburg School of Medicine, Pittsburgh, PA;

#Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA; and

**Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA

Correspondence to: Gordana Halec, PhD, David Geffen School of Medicine at UCLA, UCLA AIDS Institute, 615 Charles Young Drive, Los Angeles, CA 90095-7363 (e-mail:

Supported in part by a supplement to U01-AI-035040, by R01-CA-168482, and by the Pendleton Charitable Trust and the McCarthy Family Foundation. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional cofunding from the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute of Mental Health (NIMH). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute on Deafness and Communication Disorders (NIDCD). MACS data collection is also supported by UL1-TR001079 (JHU ICTR) from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH), Johns Hopkins ICTR, or NCATS. The MACS web site is located at

The authors have no conflicts of interest to disclose.

Data in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS). MACS (Principal Investigators): Johns Hopkins University Bloomberg School of Public Health (Joseph Margolick and Todd Brown), U01-AI35042; Northwestern University (S.W.), U01-AI35039; University of California, Los Angeles (R.D., O.M.-M., and Otto Yang), U01-AI35040; University of Pittsburgh (Charles Rinaldo, Lawrence Kingsley, and Jeremy Martinson), U01-AI35041; the Center for Analysis and Management of MACS, Johns Hopkins University Bloomberg School of Public Health (Lisa Jacobson and G.D.), UM1-AI35043.

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Received April 23, 2018

Accepted August 10, 2018

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