Title

Inflammation and tissue damage: Causes and repair mechanisms (CME)

Code

SY43

Session Type

Symposium

Track

Track A: Basic science

Channel

Channel 4

Date Time

20 July 15:00- 15:50

Local Date Time

15:00 - 15:50 W. Europe Daylight Time

Moderators:

Melissa CHURCHILL, RMIT University, Australia
Jacob ESTES, Oregon Health & Science University, United States

The underlying mechanisms of inflammation are still a matter of debate. Tissue damage can occur early, especially when ART is initiated in the chronic stage. Inflammation persists in long-term treated people living with HIV. Participants will explore these topics and discuss if there are better strategies to repair HIV-associated inflammation and tissue damage.

2 min	Introduction Melissa CHURCHILL, RMIT University, Australia Jacob ESTES, Oregon Health & Science University, United States

8 min	Inflammation and tissue damage in the CNS in the ART era Tricia BURDO, Temple University, United States	Slides

10 min	Impact of ART on adipose tissues in HIV infection Claire LAGATHU, Inserm UMRS938, Sorbonne universite, saint Antoine research Centre and ICAN in Paris, France	PDF

10 min	Therapies targeting tissue inflammation and viral persistence Mirko PAIARDINI, Emory University, United States	Slides

18 min	Live Q&A Claire LAGATHU, Inserm UMRS938, Sorbonne universite, saint Antoine research Centre and ICAN in Paris, France Tricia BURDO, Temple University, United States Melissa CHURCHILL, RMIT University, Australia Jacob ESTES, Oregon Health & Science University, United States Mirko PAIARDINI, Emory University, United States

AUTHOR

Marta Massanella

SUMMARY

This session, chaired by Jacob Estes, highlighted the central role of inflammation in HIV pathogenesis during ART, including tissue damage and viral persistence. Three distinct affected compartments (i.e., CNS, adipose tissue and lymph nodes) are presented and strategies to restore dysfunction are explored.

HIGHLIGHTS

Tricia BURDO presented that brain is multifaceted: while cerebral blood flow is dependent of age and VL (correlating negatively with sCD14), structural aging is accelerated in PWH (independently of VL), and is associated with lower CD4/CD8 ratio and increased inflammatory monocytes. Decreased brain volume and inflammatory monocytes correlate with neurocognitive impairment. Claire LAGATHU showed that both, HIV and ART (older and current regimens), cause different adipose tissue alterations. InSTI-containing regimens may induce fibrosis, adipocyte hypertrophy and insulin resistance, which can be caused by direct effect on mitochondrial metabolism of immune cells such as CD4 T cells. Mirko PAIARDINI explored different interventions targeting tissue inflammation and viral persistence: 1) IL-21 has a potent anti-inflammatory component and may reduce replication-competent virus; 2) Immune checkpoint blockers favour latency reversal, while promoting proliferation of T cells (including infected cells); 3) anti-IL10 antibodies reduce survival of lymph node Tfh cells, a cellular niche of viral persistence.

CRITICAL ASSESSMENT

We have seen a great session (and discussion) that clearly revealed that effective cure strategies require to target multiple components: reduce inflammation and stimulate immune response, with the ultimate goal to eliminate the HIV reservoir. It is essential to test the combination of different therapeutic strategies with synergistic effect [WHICH], but it is also very important to investigate WHEN to use them and identify the interplay between interventions [HOW]. Some of the deleterious effects of the virus and the overall persistent inflammation are not reversible, such as fibrosis of adipose tissue and brain structure, causing permanent damage.