Colleen Kelley

For HIV negative persons, mucosal inflammation associated with a perturbed microbiome can increase acquisition risk and, in HIV positive persons, microbial dysbiosis in the gut is associated with systemic inflammation and microbial translocation. This poster discussion session reviewed interesting findings between the microbiome and inflammation from 7 studies.

Among HIV exposed compared to HIV unexposed infants, distinct differences exist between the gut bacterial and viral composition. Data from a study examining gut glycosylation showed that it is associated with markers of microbial diversity, immune activation, and with HIV DNA levels in the gut. Data were presented showing that a novel biomarker, REG3a, may be a useful systemic marker of gut integrity for use in clinical trials attempting to reduce microbial translocation. One study showed decreased markers of systemic inflammation and microbial translocation after HCV cure in HIV/HCV positive women from the WIHS cohort suggesting a potential mechanism for the improvements in non-hepatic morbidity that are seen after HCV cure. Finally, three presentations focused on the effects of contraceptives with alterations in the female genital tract microbiome and inflammation. Findings across the studies were generally inconsistent and did not support marked increased in inflammation with DMPA use as hypothesized.

Overall, very thought-provoking data were presented in this session. As a field, we are learning much more about the possible mechanistic interactions between the microbiome and mucosal/systemic inflammation. More data are needed to define the virome and its effects on human health. The use of systemic markers of gut integrity to understand the benefits or harms of interventions will give additional insight into clinical outcomes. The recent negative ECHO trial results showing no increased risk of HIV acquisition with women using DMPA will be further contextualized by understanding the mucosal immune environment in contraceptive users.

Angela Wahl

This session on HIV and the mucosal microbiome focused on: 1) the microbiome of HIV-uninfected infants born to HIV-positive women, 2) determinants of gut dysbiosis, microbial translocation, and inflammation and 3) the effect of hormonal contraceptives on the vaginal microbiome and HIV acquisition risk.

Brian Brown presented that the gut virome of HIV-exposed uninfected infants is more diverse compared to non-HIV-exposed uninfected infants. Leila Giron showed increased sialidase levels in ART-suppressed individuals and a positive-correlation between hypo-sialylated glycan levels and sCD163 and HIV-DNA levels in the ileum. Stéphane Isnard showed that plasma levels of REG3α, a marker of gut permeability, are elevated in HIV-positive people and positively-correlated with inflammatory marker levels and integrated HIV-DNA levels in CD4+ T cells. In post-hoc analyses of CAPRISA004, Laura Noel-Romas and Refilwe Molatlhegi observed more pronounced DMPA-associated inflammation in women with a lactobacillus-dominant vaginal microbiome and a negative-correlation between MPA levels and G-CSF and M-CSF levels. In the ECHO trial, Heather Jaspan observed no DMPA-associated increase in genital inflammation or vaginal HIV acquisition despite increased genital tract Th17-like cells. Audrey French showed that sCD14 and sCD163 levels, markers of microbial translocation, decrease in HIV-positive women following HCV eradication.

Although HIV-exposed uninfected infants have a distinct and more diverse gut virome, further studies are needed to determine if these observations have a physiologic impact on infant health. Manipulating intestinal sialic acid catabolism may allow the design of novel strategies to prevent/delay the development of HIV-associated co-morbidities. Higher powered clinical studies are needed to resolve the role of DMPA in genital inflammation and vaginal HIV acquisition risk. Long-term studies of HIV-positive, HCMV cured people are needed to determine if HCV cure can lead to a reduction in the occurrence of HIV-associated non-AIDS comorbidities by reducing microbial translocation.