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Clin Infect Dis. 2019 May 2. pii: ciz329. doi: 10.1093/cid/ciz329. [Epub ahead of print]

Association of immunosuppression and HIV viremia with anal cancer risk in persons living with HIV in the United States and Canada.

Author information

1
Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale School of Medicine, New Haven, CT, USA.
2
Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
3
Department of Biostatistics, Yale School of Public Health, Yale School of Medicine, New Haven, CT, USA.
4
Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
5
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
6
Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, CA, USA.
7
Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
8
Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.
9
Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
10
Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
11
Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Rockville, MD, USA.
12
Epidemiology Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.
13
Department of Medicine, University of California San Diego, San Diego, CA, USA.
14
Retrovirus Research Center, Department of Medicine, Universidad Central del Caribe School of Medicine, Bayamon, Puerto Rico.
15
Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
16
Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; and Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
17
Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA; Department of Health Policy and Management, Yale School of Public Health, Yale School of Medicine, New Haven, CT, USA; and Research Service, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.
18
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
19
Department of Environmental Health Sciences, Yale School of Public Health, Yale School of Medicine, New Haven, CT, USA.

Abstract

BACKGROUND:

People living with HIV (PLWH) have a markedly elevated anal cancer risk largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk.

METHODS:

We studied 102,777 PLWH during 1996-2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures calculated within pre-specified moving time windows. We compared models using the Akaike's information criterion.

RESULTS:

Cumulative and nadir/peak CD4 or HIV RNA measures from ~8.5 to ~4.5 years in the past were generally better predictors for anal cancer risk than their corresponding measures from ~4.5 years to ~6 months in the past. However, the best model included CD4 nadir (i.e., the lowest CD4) from ~8.5 years to ~6 months in the past (hazard ratio for <50 vs. ≥500 cells/µL: 13.4; 95% confidence interval: 3.5-51.0) and proportion of time CD4 <200 cells/µL from ~8.5 to ~4.5 years in the past (a cumulative measure; hazard ratio for 100% vs. 0% of time: 3.1; 95% confidence interval: 1.5-6.6).

CONCLUSIONS:

Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk.

KEYWORDS:

CD4+ T-cell count; HIV infection; HIV-1 RNA viral load; anal cancer; risk

PMID:
31044245
DOI:
10.1093/cid/ciz329

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