TY - JOUR
T1 - Systemic Immune Activation and HIV Shedding in the Female Genital Tract
AU - Spencer, Lashonda Y.
AU - Christiansen, Shawna
AU - Wang, Chia Hao H.
AU - Mack, Wendy J.
AU - Young, Mary
AU - Strickler, Howard D.
AU - Anastos, Kathryn
AU - Minkoff, Howard
AU - Cohen, Mardge
AU - Geenblatt, Ruth M.
AU - Karim, Roksana
AU - Operskalski, Eva
AU - Frederick, Toni
AU - Homans, James D.
AU - Landay, Alan
AU - Kovacs, Andrea
N1 - Funding Information:
Supported by grant RO1 AI052065 (K.A.) (R01 and R56) from the National Institute of Allergy and Infectious Diseases and grant R01 CA85178 (H.D. S.) from National Cancer Institute. The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases, with additional cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Mental Health. Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research, the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Deafness and other Communication Disorders, and the NIH Office of Research on Women''s Health. WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA) and UL1-TR000454 (Atlanta CTSA). Data in this article were collected by the Women''s Interagency HIV Study (WIHS). 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. 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 (K. Anastos), U01-AI-035004; Brooklyn WIHS (H. Minkoff and Deborah Gustafson), U01-AI-031834; Chicago WIHS (M. Cohen), U01-AI-034993; Metropolitan Washington WIHS (M. Young), 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 (Alexandra Levine and Marek Nowicki), U01-HD-032632 (WIHS I-WIHS IV).
Publisher Copyright:
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Background: Plasma HIV RNA is the most significant determinant of cervical HIV shedding. However, shedding is also associated with sexually transmitted infections (STIs) and cervical inflammation. The mechanism by which this occurs is poorly understood. There is evidence that systemic immune activation promotes viral entry, replication, and HIV disease progression. We hypothesized that systemic immune activation would be associated with an increase in HIV genital shedding. Methods: Clinical assessments, HIV RNA in plasma and genital secretions, and markers of immune activation (CD38 + DR + and CD38-DR-) on CD4 + and CD8 + T cells in blood were evaluated in 226 HIV+ women enrolled in the Women's Interagency HIV Study. There were 569 genital evaluations of which 159 (28%) exhibited HIV RNA shedding, defined as HIV viral load >80 copies per milliliter. We tested associations between immune activation and shedding using generalized estimating equations with logit link function. Results: In the univariate model, higher levels of CD4 + and CD8 + T-cell activation in blood were significantly associated with genital tract shedding. However, in the multivariate model adjusting for plasma HIV RNA, STIs, and genital tract infections, only higher levels of resting CD8 + T cells (CD38-DR-) were significantly inversely associated with HIV shedding in the genital tract (odds ratios 0.44, 95% confidence interval: 0.21 to 0.9, P 0.02). Conclusions: The association of systemic immune activation with genital HIV shedding is multifactorial. Systemic T-cell activation is associated with genital tract shedding in univariate analysis but not when adjusting for plasma HIV RNA, STIs, and genital tract infections. In addition, women with high percentage of resting T cells are less likely to have HIV shedding compared with those with lower percentages. These findings suggest that a higher percentage of resting cells, as a result of maximal viral suppression with treatment, may decrease local genital activation, HIV shedding, and transmission.
AB - Background: Plasma HIV RNA is the most significant determinant of cervical HIV shedding. However, shedding is also associated with sexually transmitted infections (STIs) and cervical inflammation. The mechanism by which this occurs is poorly understood. There is evidence that systemic immune activation promotes viral entry, replication, and HIV disease progression. We hypothesized that systemic immune activation would be associated with an increase in HIV genital shedding. Methods: Clinical assessments, HIV RNA in plasma and genital secretions, and markers of immune activation (CD38 + DR + and CD38-DR-) on CD4 + and CD8 + T cells in blood were evaluated in 226 HIV+ women enrolled in the Women's Interagency HIV Study. There were 569 genital evaluations of which 159 (28%) exhibited HIV RNA shedding, defined as HIV viral load >80 copies per milliliter. We tested associations between immune activation and shedding using generalized estimating equations with logit link function. Results: In the univariate model, higher levels of CD4 + and CD8 + T-cell activation in blood were significantly associated with genital tract shedding. However, in the multivariate model adjusting for plasma HIV RNA, STIs, and genital tract infections, only higher levels of resting CD8 + T cells (CD38-DR-) were significantly inversely associated with HIV shedding in the genital tract (odds ratios 0.44, 95% confidence interval: 0.21 to 0.9, P 0.02). Conclusions: The association of systemic immune activation with genital HIV shedding is multifactorial. Systemic T-cell activation is associated with genital tract shedding in univariate analysis but not when adjusting for plasma HIV RNA, STIs, and genital tract infections. In addition, women with high percentage of resting T cells are less likely to have HIV shedding compared with those with lower percentages. These findings suggest that a higher percentage of resting cells, as a result of maximal viral suppression with treatment, may decrease local genital activation, HIV shedding, and transmission.
KW - HIV genital tract shedding
KW - T-cell activation
KW - immune activation
UR - http://www.scopus.com/inward/record.url?scp=84955688910&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84955688910&partnerID=8YFLogxK
U2 - 10.1097/QAI.0000000000000823
DO - 10.1097/QAI.0000000000000823
M3 - Article
C2 - 26334738
AN - SCOPUS:84955688910
SN - 1525-4135
VL - 71
SP - 155
EP - 162
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 2
ER -
