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Higher Body Mass Index Is Associated With Greater Proportions of Effector CD8+ T Cells Expressing CD57 in Women Living With HIV

Reid, Michael J. A. MD, MPH*; Baxi, Sanjiv M. MD, PhD, MPH; Sheira, Lila A. MPH; Landay, Alan L. PhD§; Frongillo, Edward A. PhD; Adedimeji, Adebola PhD; Cohen, Mardge H. MD#; Wentz, Eryka MA**; Gustafson, Deborah R. PhD††; Merenstein, Daniel MD‡‡; Hunt, Peter W. MD*,‡; Tien, Phyllis C. MD*,§§; Weiser, Sheri D. MD, MA, MPH*,‡; for the Women's Interagency HIV Study (WIHS)

JAIDS Journal of Acquired Immune Deficiency Syndromes: 15 August 2017 - Volume 75 - Issue 5 - p e132–e141
doi: 10.1097/QAI.0000000000001376
Translational Research

Background: A low proportion of CD28CD8+ T cells that express CD57 is associated with increased mortality in HIV infection. The effect of increasing body mass index (BMI) changes in the proportion of CD57+CD28CD8+ T cells among HIV-infected individuals on antiretroviral therapy is unknown.

Setting: In a US cohort of HIV-infected women, we evaluated associations of BMI and waist circumference with 3 distinct CD8+ T cell phenotypes: % CD28CD57+CD8+ T cells, % CD57+ of CD28CD8+ T cells, and % CD28 of all CD8+ T cells.

Methods: Multivariable linear regression analysis was used to estimate beta coefficients for each of 3 T-cell phenotypes. Covariates included HIV parameters (current and nadir CD4, current viral load), demographics (age, race, income, and study site), and lifestyle (tobacco and alcohol use) factors.

Results: Of 225 participants, the median age was 46 years and 50% were obese (BMI >30 m2/kg). Greater BMI and waist circumference were both associated with higher % CD28CD57+CD8+ T cells and % CD57+ of all CD28CD8+ T cells in multivariable analysis, including adjustment for HIV viral load (all P < 0.05). The association between greater BMI and the overall proportion of CD28 CD8+ cells in fully adjusted models (0.078, 95% confidence interval: −0.053 to 0.209) was not significant.

Conclusions: In this analysis, greater BMI and waist circumference are associated with greater expression of CD57 on CD28CD8+ T cells and a greater proportion of CD57+CD28 CD8+ T cells. These findings may indicate that increasing BMI is immunologically protective in HIV-infected women. Future research is needed to understand the prognostic importance of these associations on clinical outcomes.

*Department of Medicine, University of California, San Francisco (UCSF), San Francisco, CA;

Department of Epidemiology and Biostatistics, UCSF, San Francisco, CA;

San Francisco General Hospital, Division of HIV, ID and Global Medicine, San Francisco, CA;

§Department of Immunology-Microbiology, Rush University, Chicago, IL;

Arnold School of Public Health, University of South Carolina, Columbia, SC;

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY;

#Department of Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL;

**Women's Interagency HIV Study (WIHS) Data Management and Analysis Center (WDMAC), Johns Hopkins University, Baltimore, MD;

††Department of Neurology, State University of New York - Downstate, Brooklyn;

‡‡Department of Family Medicine, Georgetown University, Washington, DC; and

§§San Francisco Veterans Affairs Medical Center, San Francisco, CA.

Correspondence to: Michael J. A. Reid, MD, MPH, University of California San Francisco, 513 Parnassus Avenue, Room S380, San Francisco, CA 94110 (e-mail: Michael.Reid2@ucsf.edu).

Supported in part by R01-MH095683-01A1 to S.D.W. Data in this analysis were collected by the Women's Interagency HIV Study (WIHS). The contents of this analysis are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). WIHS (principal investigators): UAB-MS WIHS (Michael Saag, Mirjam-Colette Kempf, and Deborah Konkle-Parker), U01-AI-103401; Atlanta WIHS (Ighovwerha Ofotokun and Gina Wingood), U01-AI-103408; Bronx WIHS (Kathryn Anastos), U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), U01-AI-031834; Chicago WIHS (Mardge Cohen and Audrey French), U01-AI-034993; Metropolitan Washington WIHS (Mary Young and Seble Kassaye), U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch), U01-AI-103397; UNC WIHS (Adaora Adimora), U01-AI-103390; Connie Wofsy Women's HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat, and Phyllis Tien), U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), U01-AI-042590; Southern California WIHS (Joel Milam), U01-HD-032632 (WIHS I – WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Deafness and other Communication Disorders (NIDCD), and the NIH Office of Research on Women's Health. WIHS data collection are also supported by UL1-TR000004 (UCSF CTSA) and UL1-TR000454 (Atlanta CTSA). S.M.B. and M.J.A.R. were both supported by the UCSF Traineeship in AIDS Prevention Studies (US National Institutes of Health (NIH) T32 MH-19105). The funders did not play a role in study design, collection, analysis, interpretation of data, writing the report, or the decision to submit the report for publication. P.C.T. was also supported by K24 AI108516.

The authors have no conflicts of interest to disclose.

Research idea and study design: M.J.A.R., S.M.B., A.L.L., E.A.F., P.H., P.C.T., and S.D.W.; data acquisition: M.J.A.R., S.M.B., L.A.S., A.L.L., M.H.C., P.C.T., and S.D.W.; data analysis/interpretation: M.J.A.R., S.M.B., A.L.L., E.A.F., P.H., P.C.T., and S.D.W.; statistical analysis: L.A.S.; supervision or mentorship: E.A.F., P.H., P.C.T., and S.D.W. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. S.D.W. takes full responsibility that this study has been reported honestly, accurately, and transparently; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

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Received December 09, 2016

Accepted March 06, 2017

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