Plasma and Mucosal HIV Viral Loads Are Associated With Genital Tract Inflammation in HIV-Infected Women

Herold, Betsy C. MD*,†,‡; Keller, Marla J. MD†,§; Shi, Qiuhu PhD; Hoover, Donald R. PhD; Carpenter, Colleen A. BS*; Huber, Ashley BS*; Parikh, Urvi M. PhD#; Agnew, Kathy J. BS**; Minkoff, Howard MD††; Colie, Christine MD‡‡; Nowicki, Marek J. PhD§§; D'Souza, Gypsyamber PhD‖‖; Watts, D. Heather MD¶¶; Anastos, Kathryn MD†,§,##

JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e3182961cfc
Clinical Science
Abstract

Background: Systemic and mucosal inflammation may play a role in HIV control. A cross-sectional comparison was conducted among women in the Women's Interagency HIV Study to explore the hypothesis that compared with HIV-uninfected participants, women with HIV, and, in particular, those with high plasma viral load (PVL) have increased levels of mucosal and systemic inflammatory mediators and impaired mucosal endogenous antimicrobial activity.

Methods: Nineteen HIV-uninfected, 40 HIV-infected on antiretroviral therapy (ART) with PVL ≤ 2600 copies/mL (low viral load) (HIV+-LVL), and 19 HIV-infected on or off ART with PVL >10,000 (high viral load) (HIV+-HVL) were evaluated. Immune mediators and viral RNA were quantified in plasma and cervicovaginal lavage (CVL). The CVL antimicrobial activity was also determined.

Results: Compared to HIV-uninfected participants, HIV+-HVL women had higher levels of mucosal but not systemic proinflammatory cytokines and chemokines, higher Nugent scores, and lower Escherichia coli bactericidal activity. In contrast, there were no significant differences between HIV+-LVL and HIV-uninfected controls. After adjusting for PVL, HIV genital tract shedding was significantly associated with higher CVL concentrations of IL-6, IL-1β, MIP-1α, and CCL5 (RANTES) and higher plasma concentrations of MIP-1α. High PVL was associated with higher CVL levels of IL-1β and RANTES, as well as with higher Nugent scores, lower E. coli bactericidal activity, smoking, and lower CD4 counts; smoking and CD4 count retained statistical significance in a multivariate model.

Conclusions: Further study is needed to determine if the relationship between mucosal inflammation and PVL is causal and to determine if reducing mucosal inflammation is beneficial.

Author Information

Departments of *Pediatrics;

Obstetrics & Gynecology and Women's Health;

Microbiology and Immunology;

§Medicine, Albert Einstein College of Medicine, Bronx, NY;

New York Medical College, Valhalla, NY;

Institute for Health, Health Care Policy and Aging Research, Rutgers University, Piscataway, NJ;

#University of Pittsburgh, Pittsburgh, PA;

**University of Washington, Seattle, WA;

††Maimonides Medical Center, Brooklyn, NY;

‡‡Georgetown University Medical Center, Washington, DC;

§§University of Southern California, Los Angeles, CA;

‖‖Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;

¶¶Pediatric, Adolescent and Maternal AIDS Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD; and

##Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx NY.

Correspondence to: Betsy C. Herold, MD, Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forchheimer 702, Bronx, NY 10461 (betsy.herold@einstein.yu.edu).

The Women's Interagency HIV Study (WIHS) is supported by the National Institute of Allergy and Infectious Diseases Grants UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590 and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant UO1-HD-32632. The study was also supported in part by Grants U19AI067980, R01AI065309, R33AI079763 and the Center for AIDS Research at the Albert Einstein College of Medicine and Montefiore Medical Center Grant NIH AI-51519. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

The authors have no conflicts of interest to disclose.

Data in this manuscript were collected by the WIHS Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (K. Anastos); Brooklyn, NY (H. Minkoff); Washington DC Metropolitan Consortium (Mary Young); Los Angeles County/Southern California Consortium (Alexandra Levine); Data Coordinating Center (Stephen Gange).

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Received December 21, 2012

Accepted March 26, 2013

© 2013 by Lippincott Williams & Wilkins