| Key Questions |
Does the microbiome (bacterial, viral, fungal) play a contributory role in HIV comorbidities?
Are microbiome changes during HIV infection mainly a consequence of gut epithelial or immune damage, or are they a contributor to, or perpetuator of, this damage, microbial translocation, and/or systemic inflammation and comorbidities? Are changes in the virome (gut, plasma, oral, vaginal) contributors to systemic inflammation and/or end-organ comorbidities, or markers of immunological or barrier dysfunction? How do HIV-associated microbiome alterations at mucosal sites beyond the gut (eg, lung, oral) affect comorbidities such as cancer, chronic lung disease, CVD or CNS disease, or others?
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How do other cofactors interact with HIV infection to affect the microbiome and comorbidi-ties?
Do ART, geography, diet, smoking, sexual behavior, gender, and other factors impact the microbiome and its function in HIV-associated comorbidities? How do coinfections, particularly those that are prevalent in resource-poor areas and may be considered part of the “microbiome” in those areas (eg, candida, GI helminths, malaria, EBV, HHV-8) impact comorbidities directly or via effects on the more conventional gut microbiome?
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What are the mechanisms of host/HIV/microbiome interactions?
What are the responsible mediators (protein, carbohydrate, small-molecule metabolites, etc), and how do microbial products influence the host metabolome and vice-versa? How does ART impact these pathways? Beyond taxonomy, what functional changes to the microbiome are involved in these mechanisms?
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| Can the microbiome in HIV be manipulated to modify these pathways-via replacement, microbe targeting, microbe-directed small-molecule therapeutics, or other approaches? Would such approaches also need to target injured mucosa to achieve sustained impact? |
