P7. Gut microbiota diversity correlates with immune status in HIV-1 infection.

Piotr Nowak1, Marius Troseid2, 3, Ekatarina Avershina4, Babilonia Barqasho5, Ujjwal Neogi5, Johannes R. Hov 3, Kajsa Noyan5, Jan Vesterbacka1, Knut Rudi4, Anders Sönnerborg1,5.

Affiliates: 1Department of Medicine Huddinge, Unit of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; 2Department of Infectious Diseases, Oslo University Hospital, Ullevål Hospital, Oslo, Norway; 3K.G. Jebsen Centre for Inflammation Research, University of Oslo, Oslo, Norway; 4Norwegian University of Life Sciences, Ås, Norway; 5Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

Background
Progressive HIV-1 infection is characterized by dysregulation of the intestinal barrier and systemic inflammation, in part driven by translocation of immunostimulatory microbial products. However, little is known on the role of gut microbiota alterations in the pathogenesis, and whether the microbiota is restored by antiretroviral treatment (ART).

Methods
We conducted a prospective, observational study including 28 viremic patients, three elite controllers, and nine uninfected controls. Fecal microbiota composition was determined by 16S rRNA sequencing at baseline and for 19 patients at follow up during ART (median 10 months [4-15]). Soluble markers of microbial translocation and monocyte activation were analyzed by LAL assay (for LPS) or ELISA (for sCD14, LBP, sCD163).

Results
Several alpha diversity measures, including number of observed bacterial species and Shannon alpha diversity index, were significantly lower in viremic patients compared to uninfected controls, whereas the microbiota of elite controllers resembled that of the controls. In viremic patients, alpha diversity correlated significantly with CD4+ T cell counts, markers of microbial translocation, and monocyte activation. In multivariate linear regression, for every age- and gender-adjusted increase in number of bacterial species, the CD4+ T cell count increased with 0.88 (95% CI 0.35-1.41) cells /µl (p=0.002). After introduction of ART, microbiota alterations persisted with further reduction in alpha diversity (p<0.001). The changes of the bacterial taxa within the individuals were reflected by the overall significant (p<0.001) increase in beta diversity. Additionally, the microbiota composition at follow up changed for several taxa on phylum and genus level, with a significant reduction in Prevotella genus after adjustment for multiple testing (p=0.007).We could not observe any influence of different ART regimes (NNRTI vs. PI) on richness or intra/inter diversity at follow up.

Conclusions
The gut microbiota is altered in HIV-1 infected patients. Our data implicate that re-shaping the microbiota may be an adjuvant therapy even in patients commencing successful ART.