6th IAS Conference On HIV Pathogenesis, Treatment and Prevention

Reservoirs and Mechanism of Disease Progression MOAA01
Type:
Oral Abstract Session Back
Venue: SR 2
Time: 11:00 - 12:30, 18.07.2011
Code: MOAA01
Chairs: Andrea Savarino, Italy
Andrea Cossarizza, Italy



Presentations in this session:

11:00

Powerpoint		Introduction
Presented by Andrea Savarino, Italy



11:00
MOAA0101
Abstract
Powerpoint
Slides with audio		Differential impact of IL-7 and IL-15 on HIV reservoir persistence
Presented by Claire Vandergeeten, United States
C. Vandergeeten1, S. Da Fonseca1, I. Sereti2, M. Lederman3, R.-P. Sekaly1, N. Chomont1
1Vaccine and Gene Therapy Institute, Port St Lucie, United States, 2NIAID, Bethesda, United States, 3Case Western University, Cleveland, United States

11:10
MOAA0102
Abstract
Powerpoint
Slides with audio		The PI3K signaling pathway is critical for HIV integration in latently infected resting CD4+T-cells
Presented by Suha Saleh, Australia
S. Saleh1, P. Cameron1,2, G. Sallmann1, A. Joworowski1,3, S. Lewin1,2,3
1Monash University, Medicine, Melbourne, Australia, 2Infectious Disease Unit of Alfred Hospital, Melbourne, Australia, 3Burnet Institute, Melbourne, Australia

11:20
MOAA0103
Abstract
Powerpoint
Slides with audio		Effect of intensification of long-term highly active antiretroviral therapy (HAART) with raltegravir on proviral HIV-1 DNA in gut associated lymphoid tissue (GALT): a randomized, placebo controlled trial
Presented by Jason Brunetta, Canada
C. Kovacs1, J. Brunetta1, T.-W. Chun2, G. Smith1, R. Halpenny3, D. Su4, O. Mario5, G. Kandel5, R. Kaul4, J. Raboud4, M. Loutfy1
1Maple Leaf Medical Clinic, Toronto, Canada, 2National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States, 3Canadian Immunodeficiency Research Collaborative, Toronto, Canada, 4University Health Network, Toronto, Canada, 5St. Michael's Hospital, Toronto, Canada

11:30
MOAA0104
Abstract
Powerpoint
Slides with audio		The effect of HIV-infection and highly-active anti-retroviral therapy on the human gut microbiome investigated by phylogenetic-targeted 454 pyrosequencing: a meta-genomic profile of duodenal biopsies, aspirates, and stool over time
Presented by Collin L. Ellis, United States
C.L. Ellis1, C.-S. Li2, S. Mann3, Z.-M. Ma4, H. Overman2, A. Maniar1, T. Yotter1, E. Tsuchida5, T.H. Knight1, J.C. Rutledge1, C.J. Miller1,4, R.B. Pollard1, D.M. Asmuth1
1University of California Davis School of Medicine, Internal Medicine, Sacramento, United States, 2University of California Davis, Davis, United States, 3Mather Veteran's Administration Hospital, Internal Medicine, Mather, United States, 4California National Primate Research Center, Davis, United States, 5CARES Clinic, Sacramento, United States

11:40
MOAA0105
Abstract
Powerpoint
Slides with audio		Impact of tryptophan catabolism on CD4+ T cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy
Presented by Peter W. Hunt, United States
P. Hunt1, S. Weiser1, Y. Huang1, C. Muzoora2, A. Kembabazi2, K. Ragland1, J. Bennett1, S. Deeks1, D. Bangsberg3, J. Martin1, J. McCune1
1University of California - San Francisco, San Francisco, United States, 2Mbarara University of Science and Technology, Mbarara, Uganda, 3Massachusetts General Hospital, Center for Global Health, Boston, United States

11:50
Moderated discussion

Powerpoints presentations
Introduction - Andrea Savarino

Differential impact of IL-7 and IL-15 on HIV reservoir persistence - Claire Vandergeeten

The PI3K signaling pathway is critical for HIV integration in latently infected resting CD4+T-cells - Suha Saleh

Effect of intensification of long-term highly active antiretroviral therapy (HAART) with raltegravir on proviral HIV-1 DNA in gut associated lymphoid tissue (GALT): a randomized, placebo controlled trial - Jason Brunetta

The effect of HIV-infection and highly-active anti-retroviral therapy on the human gut microbiome investigated by phylogenetic-targeted 454 pyrosequencing: a meta-genomic profile of duodenal biopsies, aspirates, and stool over time - Collin L. Ellis

Impact of tryptophan catabolism on CD4+ T cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy - Peter W. Hunt



Rapporteur reports

Track A report by Giulia Marchetti


Within the oral session MOAA01, interesting data were shown by C. Vandergeeten on the differential impact of IL-7 and IL-15 on HIV reservoir persistence. The authors focused on the role of the gc-cytokines IL-7 and IL-15 in maintaining the pool of latently infected CD4 on virologycally-suppressive HAART, given their major role as promoters of CD4+ T-cell proliferation/survival. Following cytokine stimulation of CD4+, IL-7 resulted in higher proportion of proliferating Ki67+CD4+, but viral reactivation was increased only following IL-15 stimulation, suggesting that IL-15 induces viral reactivation with minimal effect on proliferation. S. Saleh provided in vitro data showing that PI3K antagonists result in complete elimination of integrated DNA but only slight change in nuclear-localised DNA (2-LTR), suggesting that strategies that target these pathways may potentially lead to novel interventions to block the establishment of latent infection. J Brunetta presented data from a small double-blinded placebo-controlled raltegravir intensification study on HIV+ patients on long-term virologically-suppressive HAART. No differences were detected in blood and sigmoid samples HIV DNA by wk48.
C.L. Ellis comparatively investigated the intestinal microbioma in duodenal biopsies and aspirate and stool (phylogenetic-targeted 454 pyrosequencing) given the hypothesis that it may influence inflammation in HIV. This high-throughput assay allowed a broader sequencing of previously unidentified bacterial taxa: greater representation of proinflammatory/inflammation-thriving class-level bacteria were shown. They also observed unique distributions of bacteria in samples from different anatomical sites which were not clearly impacted by HAART therapy.
P. Hunt demonstrated that levels of tryptophan predicted both CD4+ recovery and death in 435 Ugandan adults starting antiretroviral therapy.Dietary protein builds tryptophan levels, but HIV infection induces tryptophan catabolism. Lower pretreatment tryptophan levels predicted slower CD4+ recovery after 12 months of therapy; lower pretreatment and month 6 tryptophan predicted death. These correlations held true when the researchers accounted for self-reported dietary protein levels.


Community Advisory Group report by David Haerry


In a very interesting session on “Reservoirs and mechanisms of disease progression”, Claire Vandergeeten demonstrated that IL-15 should be considered as a possible candidate to achieve HIV eradication.

 

Jason Brunetta presented on the effect of HAART intensification. It was based on the hypothesis that new drug classes might be able to target virus in mucosal reservoir. This approach has shown no benefit after 48 weeks of intensified HAART.

 

Collin Ellis discussed the “Effect of HIV-infection and HAART on the human gut microbiome by phylogenetic pyrosequencing. Sequencing a patient’s personal microbial genome or microbiome could help design future ancillary therapeutic interventions.

 

Finally, Peter Hunt presented on the “Impact of tryptophan catabolism on CD4+ T Cell recovery and mortality in Ungandans initiating cART”. The background to his work: immune activation persists in most HIV+ patients despite ART-mediated viral suppression. Persistant inflammation may contribute to morbidity during treated HIV-infection. Therefore, demonstrating that specific inflammatory pathways predict subsequent clinical event is a critical step in identifying therapeutic agents. He demonstrated that Tryptophan catabolism is a major independent predictor of mortality in HIV-infected Ugandans both pre-cART and during cART-mediated viral suppression. It is however unclear if tryptophan catabolism is causally associated with disease or simply another marker for monocyte and DC activation.

 

From a community perspective, it is encouraging to see that a so far neglected research area has become that productive. Preventing HIV acquisition and curing infection must be the ultimate goal of scientific research in HIV.

   

    The organizers reserve the right to amend the programme.
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