Microbial Translocation and Immune Activation in HIV-1 Infected Pregnant Women

Author(s): Charles D. Mitchell*, Sady Dominguez, Margaret Roach, Varghese George, Stefano Rinaldi, Margaret Fischl, Jonell Potter, Brittany Tyson, Savita Pahwa.

Journal Name: Current HIV Research

Volume 16 , Issue 3 , 2018

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Abstract:

Background: Immune Activation (IA) has been previously documented in both pregnant (PG) and non-PG HIV-1 infected (HIV+) women as well as in HIV- uninfected PG women; the latter as a result of the fetal allograft. To determine whether the combined effects of HIV and pregnancy result in increased IA and whether IA is associated with Microbial Translocation (MT), we performed a prospective, longitudinal, controlled study during pregnancy and the postpartum (PP) period.

Methods: HIV+ PG women had biomarkers of IA and MT tested at 12-20 weeks (T1), and 24-36 weeks (T2) of pregnancy and at 6-8 weeks Postpartum (T3). HIV+, non-PG women were tested at comparable time points. HIV- PG women were tested at T1 only. HIV+ women were not started on antiretroviral therapy (ART) until T1. Biomarkers of IA assessed included: CD4DR+, CD4CD38+, CD4DR+CD38+, CD8DR+, CD8CD38+, and CD8DR+CD38+. Biomarkers of MT included LPS, sCD14, and 16SrDNA.

Results: 30 HIV+PG women, 18 HIV+ non-PG and 10 HIV-PG were enrolled. In the HIV+ women, there were no differences in median age, viral load, % or absolute CD4 at entry. Significant differences between T1 and T2 and between T1 and T3 were noted in CD8DR+CD38+ in HIV+PG women after ART. CD4DR+, CD4DR+CD38+, and CD8DR+ decreased post ART in HIV+PG women but a decline in IA was less evident in HIV+ non-PG. LPS decreased post ART by T3 in both HIV+PG and HIV+ non-PG groups; 16SrDNA was elevated at all time points in both groups when compared to control values, and declined post ART in the HIV+PG group. A subgroup of HIV-PG at T1 had IA and MT as evidenced by several IA markers and increased LPS.

Conclusion: The degree of IA and MT was similar among HIV+PG and HIV+ non-PG women followed longitudinally. There was no incremental increase due to the combined effects of HIV and pregnancy. Several markers of IA and MT (LPS, 16SrDNA) decreased post ART. IA and MT occurred in a subgroup of HIV-PG women during the 1st trimester. Further study must be done to confirm whether MT consistently occurs in some healthy women during PG.

Keywords: Pregnant women, human immunodeficiency virus, microbial translocation, immune activation, longitudinal observational study, antiretroviral therapy.

[1]
Kourtis K, Jennifer S, Read J, Jamieson D. Pregnancy and infection. N Engl J Med 2014; 370: 2211-8.
[2]
Aagaard-Tillery K, Silver R, and Dalton J. Immunology of normal pregnancy. Semin Fetal Neonatal Med 2006; 11: 279-95.
[3]
Mikyas Y, Aziz N, Harawa N, et al. Immunologic activation during pregnancy: serial measurement of lymphocyte phenotype and serum activation molecules in HIV-infected and uninfected women. J Reprod Immunol 1997; 33: 157-70.
[4]
Burns D, Nourjah P, Wright D, et al. Changes in immune activation markers during pregnancy and postpartum. J Reprod Immunol 1999; 42: 147-65.
[5]
Truong H, Sim M, Dillon M, et al. Correlation of immune activation during late pregnancy and early postpartum with increases in plasma hiv rna, cd4/cd8 t cells, and serum activation markers. Clin Vaccine Immunol 2010; 17(12): 2024-8.
[6]
Silver R. Immune activation early in pregnancy: trouble down the road. Am J Obstet Gynecol 2008; 199(4): 327-8.
[7]
Hunt PW. Role of immune activation in hiv pathogenesis. Curr HIV/AIDS Rep 2007; 4: 42-7.
[8]
Hunt PW, Brenchley J, Sinclair E, et al. Relationship between t cell activation and cd4(+) t cell count in hiv-seropositive individuals with undetectable plasma hiv rna levels in the absence of therapy. J Infect Dis 2008; 197: 126-33.
[9]
Veazey RS, Lackner AA. HIV swiftly guts the immune system. Nat Med 2005; 11: 469-70.
[10]
Brenchley J, Price D, Schacker T, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 2006; 12: 1365-71.
[11]
Marchetti G, Bellstri GM, Borghi E, et al. microbial translocation is associated with sustained failure in cd4+ t-cell reconstitution in hiv-infected patients on long-term highly active antiretroviral therapy. AIDS 2008; 22: 2035-44.
[12]
Marchetti G, Tincati C, Silvestri G. microbial translocation in the pathogenesis of HIV infection and AIDS. Clin Microbiol Rev 2013; 26: 2-18.
[13]
Burgener A, McGowan I, and Klatt N. HIV and mucosal barrier interactions: consequences for transmission and pathogenesis. Curr Opin Immunol 2015; 36: 22-30.
[14]
Zevin A, McKinnon L, Burgener A, Klatt N. Microbial translocation and microbiome dysbiosis in HIV-associated immune activation. Curr Opin HIV AIDS 2016; 11: 182-90.
[15]
Sandler NG, Koh C, Roque A, et al. Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection. Gastroenterology 2011; 141: 1220-30.
[16]
Caradonna L, Mastronardi M, Magrone T, et al. Biological and clinical significance of endotoxemia in the course of hepatitis C virus infection. Curr Pharm Des 2002; 8: 995-1005.
[17]
Page E, Nelson M, Kelleher P. HIV and hepatitis C coinfection: Pathogenesis and microbial translocation. Curr Opin HIV AIDS 2011; 6: 472-7.
[18]
Jiang W, Lederman MM, Hunt P, et al. Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection. J Infect Dis 2009; 199: 1177-85.
[19]
Mor Gil, Aldo Paulomi, Alvero Ayesha. The unique immunological and microbial aspects of pregnancy. Nat Rev Immunol 2017; 17: 469-82.
[20]
Loewendorf A, Nguyen T, Yesayan M, Kahn D. Normal human pregnancy results in maternal immune activation in the periphery and at the uteroplacental interface. PLoS One 2014; 9: 1-13.
[21]
Hunt P, Martin J, Sinclair E, et al. Valganciclovir reduces t cell activation in HIV-infected individuals with incomplete cd41 T cell recovery on antiretroviral therapy. J Infect Dis 2011; 203: 1474-83.


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Article Details

VOLUME: 16
ISSUE: 3
Year: 2018
Page: [208 - 215]
Pages: 8
DOI: 10.2174/1570162X16666180731145011

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