Fungal Translocation Is Associated with Immune Activation and Systemic Inflammation in Treated HIV.

Abstract

The mechanisms causing HIV-associated immune activation remain incompletely understood. Alteration of intestinal integrity with subsequent translocation of bacterial products appears to play an important role; however, little is known about the impact of fungal translocation. We assessed the effect of fungal translocation and its association with immune activation in people living with HIV (PLWH) compared with uninfected controls. We measured serum levels of β-D-glucan (BDG) and anti-Saccharomyces cerevisiae antibodies (ASCA) immunoglobulin G (IgG) and immunoglobulin A (IgA) and markers of systemic inflammation and immune activation in virally suppressed PLWH on antiretroviral therapy (ART) and uninfected controls. T-test and Mann-Whitney tests were used to compare markers by HIV status and correlation and regression analyses were used to assess associations of fungal translocation markers with markers of inflammation. One hundred seventy-six participants were included (128 HIV+ and 48 HIV-); 72% male, 65% African American, median age was 50 years, and CD4 was 710 cells/cm3. Levels of BDG tended to be lower in HIV+ when compared with controls (p = .05). No significant difference in levels of ASCA IgG and IgA was seen between groups (p > .75). There was a significant correlation between BDG and several markers of inflammation and immune activation in PLWH, not seen in uninfected controls. In contrast, no correlations were seen between levels of ASCA IgG and IgA with inflammatory markers. PLWH on ART do not have higher levels of BDG or ASCA when compared with uninfected controls, however, the association found between BDG and several inflammation markers suggests a potential role of fungal translocation in the heightened immune activation seen in treated HIV.

• Authors: Lukasz D Weiner, Mauricio Retuerto, Christopher L Hager, Vanessa El Kamari, Lingpeng Shan, Abdus Sattar, Manjusha Kulkarni, Nicholas Funderburg, Mahmoud A Ghannoum, Sahera Dirajlal-Fargo, Grace A McComsey
• Journal: AIDS research and human retroviruses (AIDS Res Hum Retroviruses) Vol. 35 Issue 5 Pg. 461-472 (05 2019) ISSN: 1931-8405 [Electronic] United States
• PMID: 30784316 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Fungal
• Antiviral Agents
• Biomarkers
• Glucans
• Immunoglobulin A
• Immunoglobulin G

Topics

• Adult
• Antibodies, Fungal (blood)
• Antiviral Agents (therapeutic use)
• Biomarkers (blood)
• Cohort Studies
• Cross-Sectional Studies
• Female
• Glucans (blood)
• HIV Infections (blood, drug therapy, immunology, microbiology)
• Humans
• Immunoglobulin A (blood)
• Immunoglobulin G (blood)
• Inflammation
• Lymphocyte Activation
• Male
• Middle Aged
• Saccharomyces cerevisiae (immunology)