7th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013)


MOBS01 Immune Activation in HIV
  Bridging Session
Venue: Session Room 4
Time: 01.07.2013, 11:00 - 12:30
Co-Chairs: Anne Hosmalin, France
Doug Nixon, United States
This session is directed towards basic scientists and clinicians interested in immune activation and its role in HIV infection, disease progression and inflammation. The presenters will offer a review of what is known as well as new data on T cell activation and inflammation and will address the following questions: Is inflammation a new surrogate for HIV progression? What is inflammation's role in progression, comorbidity and mortality? What are the best biomarkers for immune activation? What is the link between inflammation and T cell activation? What could cause immune activation? What have we learnt from immunomodulatory interventions and what is coming next? The presentations will be followed by a panel discussion.

11:00
MOBS0101
Webcast
Introduction

11:05
MOBS0102
The role of immune activation in HIV pathogenesis
I. Sereti, United States

11:25
MOBS0104
Novel immunomodulatory strategies for HIV infection
M. Paiardini, United States

11:45
MOBS0103
Powerpoint
Webcast
The role of adaptive versus innate immune activation in non-AIDS morbidity
P. Hunt, United States

12:05
MOBS0105
Webcast
Questions and answers

Powerpoints presentations
The role of adaptive versus innate immune activation in non-AIDS morbidity - Peter Hunt



Rapporteur report

Track A report by Nichole Klatt


Immune Activation in HIV

This session was an overview on the role ofimmune activation during HIV infection, what biomarkers measure inflammationduring HIV, what mechanisms contribute to immune activation, and what therapiesmay intervene to decrease activation.

Irini Sereti: The Role of Immune Activation inHIV Pathogenesis

Background:

-Immune activation contributes to pathogenesis& is a predictor of mortality in HIV infection

-ARVs decrease activationbut not completely

-Biomarkers remainelevated with treated HIV Infection

-Inflammation triggerscoagulation and fibrosis

-Incomplete CD4restoration despite ARVs

Study:

-Study to understand natural history of HIV &AIDS in the era of effective therapy (SUN Study) : 691 participants naïve orexposed combination ART

-Measured biomarkers,T cell and monocyte activation

-Coronary arterycalcium (CAC) measurement

-CMV disease andimpact on inflammation

Results:

-Monoctye phenotypes (CCR5, CD16, Tissue factor,CCR2) are independently linked to biomarkers IL-6, CRP, and D-dimers

-T cell activation (CD28) marker is not linked toD-Dimers

-CD14+CD16+ monocytes independently predicted CACprogression at 2 years

-Tissue factors expressing monocyte are highlyfunctional and express multiple cytokines (IL1b, IL6 and/or TNFa)

-Thrombin induces cytokine production by humanmonocytes

-Biomarkers of coagulation (D-Dimer and tissuefactor) are elevated in elite controllers

-CMV co-infection shows high and persistentinflammation markers

-in the INSPIRE2 clinical trial several injectionsof IL-7 increases CD4 and CD8 cell counts and decreases levels of biomarkersand of neutrophil infiltration in the lamina propria.

Conclusions: Immuneactivation is critical in HIV pathogenesis, and biomarkers should be monitored,particularly biomarkers of coagulation.

Mirko Paiardini: Novel immunomodulatorystrategies for HIV infection

Background:

-Comparative AIDS research in non-human primates:

-Natural Hosts (sooty mangabey) have non-pathogenic infection (no AIDSprogression after SIV, no immune activation or microbial translocation)

-Non-natural hosts (rhesus macaques) have pathogenic infection (AIDSprogression after SIV infection, immune activation and microbial translocationsimilar to HIV)

-Immune activation due to pro-inflammatory mileuand loss of mucosal integrity

Studies performed to decrease immune activationwere:

-TNF blockade to target pro-inflammatory mileu(J. Estes)

-Decreasedinflammation slightly

-IFN blockade (G. Silvestri)

-No difference in viral load, but did reduce CD4+ T cell and B cellactivation

-Sevelamer to block microbial translocation (I.Pandrea)

-Reduced LPS, andsignificantly reduced T cell activation

-Probiotic treatment enhances mucosal immunity(N. Klatt)

-Increased GI tract CD4+ T cells and decreased GI tract immuneactivation

-IL-17 is an important cytokine in maintenance ofGI tract immunity

-Th17 cells are preferentially depleted in pathogenic SIV and HIV andassociated with progression to AIDS

Study: Modulation of IL-17 by treating with IL-21(which activates IL-17 production, increases survival of B cells and CTLs)

 -Loss of CD4+IL-21+ T cellsis associated with Th17 depletion

Results:

-IL-21 treatment issafe and does not increase viral load

-IL-21 treatmentincreases IL-17 production transiently

-IL-21 treatment isassociated with reduced GI tract and systemic immune activation

Future perspective: move on to chronic, ART-treated SIV-infected animals and Combined intervention approaches.

Peter Hunt: The role of adaptive versus innateimmune activation in non-AIDS morbidity

Background:

-Shift from targeting T cell activation toinnate/monocyte activation in the treatment of HIV during ARV treatment

-CD8+ T cell activation (CD38+HLA-DR+) predictsdeath of AIDS independent of viral load

-CD8+ T cell activation decreases after ARV butsignificantly increased compared to HIV-

-What causes disease? Is CD4 count simply amarker of AIDS and not actually causing AIDS? Possible mechanisms of disease:inflammation and activation

Studies and Results:

-SUN, SMART and SOCA studiesdemonstrated inflammation associated with all cause mortality (monocyteactivation, coagulation markers, biomarkers IL-6 and D-dimers)

-Innate activation predicts mortality morestrongly than T cell activation

-When adjusted for innate markers, CD4 count is no longer predictiveof mortality

-CD8 T cell senescence (CD28-CD57+) appears protective from mortality

-LOW CD57 on CD28- CD8+ T cells predicts mortality 5-fold (opposite ofother chronic infections such as CMV)

-Low CD57 also associated with microbial translocation

Conclusions:

-Strong evidence that inflammation and coagulation are drivers ofdisease, but T cell dysfunction, but perhaps not activation is associatednon-AIDS mortality

-sCD14 is a better marker of outcome in study designs than T cellactivation





   

    The organizers reserve the right to amend the programme.