Publications

A report of the 8th annual Pharmacogenomics and Personalized Therapy meeting, Cold Spring Harbor Laboratory, USA, 17-21 November 2010.

BACKGROUND

Although the rate of mother-to-child transmission of hepatitis C virus (HCV) is low, the effect of HCV exposure in utero on the fetal immune system is unknown.

METHODS

Umbilical cord blood was obtained from 7 neonates born to HCV-seropositive, HCV RNA-positive women and 8 neonates born to HCV-seronegative women. Cord blood mononuclear cells were analyzed by immunophenotyping and by intracellular cytokine staining after HCV-specific and polyclonal stimulation. Plasma was analyzed for anti-HCV immunoglobulin M (IgM), cytokine/granzyme concentrations, and indoleamine 2,3-dioxygenase (IDO) activity.

RESULTS

HCV-exposed neonates had significantly lower levels of regulatory T cells expressing HLA-DR, lower CD4(+) and CD8(+) T cell activation, and lower plasma levels of pro-inflammatory markers than did controls. However, CD4(+) and CD8(+) T cells from HCV-exposed neonates had higher IFN-γ production in response to polyclonal stimulation than did T cells from controls. IDO activity was similar between groups. No HCV-specific T cell responses or anti-HCV IgM were detected in any neonates.

CONCLUSIONS

HCV-exposed neonates showed a relative suppression of immune activation and pro-inflammatory markers, which was counterbalanced by an increased production capacity for IFN-γ. These results suggest that HCV encounters the fetal immune system in utero, and alters the balance between suppressive and pro-inflammatory responses.

Men who have sex with men (MSM) continue to be disproportionately affected by human immunodeficiency virus (HIV) infection. While the MSM population does better than other HIV infection risk groups with regard to linkage to and retention in care, little is known about engagement in care outcomes for important subpopulations of MSM. There is also a dearth of research on engagement in care strategies specific to the MSM population. Key MSM subpopulations in the United States on which to focus future research efforts include racial/ethnic minority, young, and substance-using MSM. Health care systems navigation may offer a promising engagement in care strategy for MSM and should be further evaluated. As is the case for HIV-infected populations in general, future research should also focus on identifying the best metrics for measuring engagement in care.