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

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; antiretroviral therapy; human immunodeficiency virus; immune activation; longitudinal observational study; microbial translocation..