Microbiome-based Stratification of Individuals at Risk of HIV-1 Acquisition, Chronic Clinical Complications, Antimicrobial Drug Resistance, and Unresponsiveness to Therapeutic HIV-1 Vaccination

Background and Rationale: The HIV/AIDS pandemic continues to be one of the major health challenges ever faced by mankind. Far from being resolved, HIV is soaring in Eastern Europe (60% increase in new infections and 27% increase in deaths since 2010) and other regions of the world despite increasing access to antiretroviral treatment . There is emerging evidence that the human microbiome impacts some of the most important clinical aspects of HIV-1 infection, including immune disorders, chronic inflammation and accelerated aging . Work in other viral diseases and cancer immunotherapy suggest a critical role of the human microbiome also in the outcome of immune therapeutic interventions in HIV-1 infection .

MISTRAL (The Microbiome-based stratification of individuals at risk of HIV-1 acquisition, chronic clinical complications, antimicrobial drug resistance, and unresponsiveness to therapeutic HIV-1 vaccination) is a European Union (EU) Horizon 2020 funded project that aims to explore the impact of the human microbiome on clinical outcomes in people living with HIV (PLWH). The MISTRAL project brings together a team of world-class HIV and microbiome researchers with ideal complementary knowledge and expertise. This team will work to discover and validate novel gut microbiome biomarkers to inform rationally designed, mechanistically-driven interventions on the gut microbiome to mitigate HIV-1 acquisition, systemic inflammation, chronic clinical complications, antimicrobial drug resistance, and boost the efficacy of HIV cure immunotherapies.

Within the MISTRAL project, the MISTRAL study will explore the impact of the microbiome on clinical outcomes in a large clinical cohort of PLWH through the collection and analysis of stool, plasma and blood samples. The MISTRAL study will utilize the long-established network, clinical sites and expertise of the EuroSIDA study, a prospective, observational cohort study of PLWH that has been collecting observational data since 1994.

The stool samples collected in the MISTRAL study will configure a microbiome repository module. The microbiome data/test results will be combined with those of other biomarkers obtainable from testing plasma and blood samples, which could result in increased efficiency and the possibility to use other biomarkers to test the relevance of specific hypothesized pathways. Ultimately, the expected outcome of the MISTRAL study is to have a better basic understanding of the pathophysiological factors of the interplay of HIV infection and the human microbiome.

Study objectives: The primary objective of the MISTRAL study is to strengthen and evaluate the understanding of the association between the gut microbiome composition and the risk of developing serious AIDS and non-AIDS events, including cardiovascular events. The second objective is to evaluate the associations between the gut microbiome composition and function and pathologic increases in inflammation and coagulation mediators in PLWH. The third objective is to develop a risk score which makes use of information in the gut microbiome as well as other risk factors separately for the different endpoints.