Poster No THPDA 0104 Accepted by Frontiers in

Poster No. THPDA 0104 Accepted by Frontiers in Microbiology on the 2 nd, July 2018 Association between Gut Microbiota and CD 4 Recovery in HIV-infected Patients Dr. Wei LU Department of Infectious Diseases Pekin Union Medical College Hospital

Background • The first case was reported in China in 1985 at PUMCH • By the end of 2017, there were totally 758, 610 living cases of HIV/AIDS in China. Transmission Routes 100 4. 34 7. 7 6. 0 10. 0 14. 2 80 21. 4 19. 1 25. 8 28. 25 19. 1 14. 7 25. 2 Percentage 12. 0 60 27. 9 29. 2 9. 1 34. 1 6. 1 40 3. 4 44. 2 65. 7 2. 5 68. 0 69. 4 66. 4 2012 2013 2014 66. 25 58. 4 48. 3 20 40. 9 38. 9 30. 6 0. 3 11. 3 0 1985– 2006 2005 Heterosex ual Chinese CDC, 2011 -2017 2008 Homosexutal 2009 IDU 2010 Blood 2011 Mother to to Child 2015 unknown

Background-Immune non-responders (INRs) Immune non-responders Immune responders 5 400 350 血浆病毒载量 4 300 250 3 200 2 150 100 1 50 50 0 0 血浆病毒载量 CD 4+ T cell count/mm 3 Viral load log 10 copies/ml 350 5 0 3 6 9 12 15 18 21 24 27 30 0 0 3 6 9 12 Antiretroviral therapy period (months) 15 18 21 24 27 0 30 3

Background-Factors influencing CD 4 recovery Many factors may contribute to immune nonresponders: - decreased thymus output function - damaged bone marrow hematopoietic function - consistent viral replication -microbial translocation -immune activation Low CD 4 nadir associated with greater longterm T-cell activation, inflammation, HIVpersistence and adverse outcome Wei Lu, et al. JIAS, 2015. REVIEW

Is there any relationship between gut microbiota with immune activation and poor CD 4 recovery In HIV-infected patients ?

Methods • Design: a cross-sectional study on four groups during 2015 -2016 in PUMCH. VU HIV viremic untreated patients (pre-ART, N=26) IR Immunologic ART Responder (on-ART after 2 years, CD 4+ T-cell counts >350 c/mm 3, N=15) INR Immunologic ART Non-Responder (on-ART after 2 years, CD 4+ T-cell counts <350 HC c/mm 3, N=20) Healthy volunteers as control (N=30) • Extraction DNA of stool • Metagenomic sequencing • T cell subsets including CD 4+ T cells and immune activation subsets (CD 8+HLA-DR+ and CD 8+CD 38+) by flow cytometry

Results (a) There were no significant differences in alpha diversity between 4 groups. (b) Beta diversity was calculated by principal coordinate analysis and non-metric multidimensional scaling which showed a clear separation of HC from other groups at the genus level.

Results Distribution of VU, IR, INR and HC in enterotypes. Untreated patients had the highest enterotype 2 Microbiota. And individuals on ART had a lower percentage of enterotype 2 but still higher than HC.

Results

Conclusions • We confirmed the gut microbiota abundance in enterotype 2 after HIV infection in Chinese HIV-1 infected patients and the diversity and composition of gut microbiota could not be recovered completely after effective ART. • We found that some gut microbiota was associated with poor CD 4 T cell recovery and involved in immune activation, which might have impact on CD 4 T cells since the beginning of HIV infection other than any ART. • Interventions to reverse gut dysbiosis and inhibit immune activation could be new strategies for immune reconstitution in HIV infected individuals.

Discussion • Limitation: cross-sectional study, limited numbers of patients • Ongoing Studies: • Longitudinal study on naïve-patients before and after ART • Animal models • Gut biopsy • Intervention Studies • Probiotics for immune non-responders patients • Chinese herb function on gut microbiota of HIV patient

Acknowledgements • Thanks to my colleagues in PUMCH directed by Dr. Taisheng Li • Thanks to Professor Baoli Zhu and his team at CAS • Thanks to Dr. Routy and BR • Thanks to my dear HIV/AIDS patients and volunteers lvweipumch@163. com