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Cumulative HIV Viremia and Non–AIDS-Defining Malignancies Among a Sample of HIV-Infected Male Veterans

Kowalkowski, Marc A. PhD*,†; Day, Rena S. PhD; Du, Xianglin L. MD, PhD; Chan, Wenyaw PhD§; Chiao, Elizabeth Y. MD, MPH‖,¶

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 October 2014 - Volume 67 - Issue 2 - p 204–211
doi: 10.1097/QAI.0000000000000289
Epidemiology and Prevention

Background: Research suggests that cumulative measurement of HIV exposure is associated with mortality, AIDS, and AIDS-defining malignancies. However, the relationship between cumulative HIV and non–AIDS-defining malignancies (NADMs) remains unclear. The aim of this study was to evaluate the effect of different HIV measures on NADM hazard among HIV-infected male veterans.

Methods: We performed a retrospective cohort study using Veterans Affairs HIV Clinical Case Registry data from 1985 to 2010. We analyzed the relationship between HIV exposure (recent HIV RNA, % undetectable HIV RNA, and HIV copy-years viremia) and NADM. To evaluate the effect of HIV, we calculated hazard ratios for 3 common virally associated NADM [ie, hepatocarcinoma (HCC), Hodgkin lymphoma (HL), and squamous cell carcinoma of the anus (SCCA)] in multivariable Cox regression models.

Results: Among 31,576 HIV-infected male veterans, 383 HCC, 211 HL, and 373 SCCA cases were identified. In multivariable regression models, cross-sectional HIV measurement was not associated with NADM. However, compared with <20% undetectable HIV, individuals with ≥80% had decreased HL [adjusted hazard ratio (aHR) = 0.62; 95% confidence interval (CI): 0.37 to 1.02] and SCCA (aHR = 0.64; 95% CI: 0.44 to 0.93). Conversely, each log10 increase in HIV copy-years was associated with elevated HL (aHR = 1.22; 95% CI: 1.06 to 1.40) and SCCA (aHR = 1.36; 95% CI: 1.21 to 1.52). Model fit was best with HIV copy-years. Cumulative HIV was not associated with HCC.

Conclusions: Cumulative HIV was associated with certain virally associated NADM (ie, HL and SCCA), independent of measured covariates. Findings underline the importance of early treatment initiation and durable medication adherence to reduce cumulative HIV burden. Future research should prioritize how to best apply cumulative HIV measures in screening for these cancers.

*Levine Cancer Institute, Carolinas Healthcare System, Charlotte, NC;

College of Health and Human Services, University of North Carolina at Charlotte, Charlotte, NC;

Department of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas School of Public Health, Houston, TX;

§Department of Biostatistics, University of Texas School of Public Health, Houston, TX;

Department of Medicine, Baylor College of Medicine, Houston, TX; and

Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX.

Correspondence to: Marc A. Kowalkowski, PhD, Levine Cancer Institute, Carolinas Healthcare System, 1021 Morehead Medical Drive, Charlotte, NC 28204 (e-mail:

At the time of the research, Dr. Kowalkowski was on staff at Baylor College of Medicine, Department of Medicine and conducted his research at the Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX.

Supported in part by resources and the use of facilities at the Center for Innovations in Quality, Effectiveness and Safety (#CIN 13-413), Michael E. DeBakey Veterans Affairs Medical Center, and the Baylor College of Medicine Dan L. Duncan Cancer Center (P30CA125123-04S1). This research was also supported by the Baylor-UTHouston Center for AIDS Research (CFAR), an NIH-funded program (AI036211).

The funders had no role in study design, data collection and analysis, or preparation of this report.

E.C. (R01CA163103) received support from the NCI. The remaining authors have no conflicts of interest to disclose.

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Received March 13, 2014

Accepted June 18, 2014

© 2014 by Lippincott Williams & Wilkins