Presentation is loading. Please wait.

Presentation is loading. Please wait.

New concepts in HIV: HIV immunopathogenesis, treatment and vaccine strategies - report back from pre-conference Nicolas Chomont VGTI-Florida.

Published byBrodie Choate Modified over 9 years ago

Similar presentations

Presentation on theme: "New concepts in HIV: HIV immunopathogenesis, treatment and vaccine strategies - report back from pre-conference Nicolas Chomont VGTI-Florida."— Presentation transcript:

1 New concepts in HIV: HIV immunopathogenesis, treatment and vaccine strategies - report back from pre-conference Nicolas Chomont VGTI-Florida

2

3

4 Christine Katlama: The HAART reality
HAART is not perfect! • Long term Toxicity • CD4/VL monitoring • Resistance • Cost New objectives for HIV therapy Increased survival, stop progression, stop transmission Decrease drug burden (number of ARV) to decrease toxicity and cost Stop HAART (at least transitorily) Functional cure / Eradication How can we measure the efficacy of interventions aimed at reducing the viral reservoirs?

5 Doug Richman: Measuring HIV persistence
Sensitivity and precision of current assays? S. Lewin and C. Rouzioux, AIDS 2011

6 Optimal suppression of viral replication

7 Mechanisms of HIV persistence
Residual viremia in treated subjects: - Ongoing viral replication? - Viral production by long lived cells? Viral replication HAART Viral production

8 Viral production: Identifying the source
Large variety of candidates: CD4 T cells Macrophages (Mario Stevenson) Hematopoietic stem cells (C. Carter and K. Collins) CNS Others We need to explore tissues (cell sorting and RNA/DNA quantification) Can we match the sequence of the virus in plasma with the sequence in other compartments? Intensification with drugs that penetrate tissues?

9 Doug Richman: Mechanisms of HIV persistence
Evidences for the absence of ongoing viral replication Little or no impact of treatment intensification No evolution (resistance to ARV) BUT Buzon et al (Nat Med 2010) observed increased levels of 2-LTR circles upon Raltegravir intensification and reduced levels of activation Yukl et al (AIDS 2010) observed an impact of HAART intensification in the ileum (unspliced HIV RNA)

10 C. Katlama: Optimal suppression of viral replication
Nevirapine is associated with a higher rate of VL<1 copy/mL when compared with EFV or LPV (Bonora, J Med Virol 2009) 40 virally suppressed patients with VL<1 copy/mL Some of them still show high levels of immune activation (n=17) which are associated with: A low Nadir CD4 A low CD4/CD8 ratio (ongoing replication somewhere, bacterial translocation?) Is residual viremia a good marker to monitor HIV persistence?

11 HIV DNA in PBMCs Acute Chronic LTNP controllers Visconti
S. Lewin and C. Rouzioux, AIDS 2011

12 The VISCONTI patients Five out of 32 patients who received very early and prolonged antiretroviral therapy showed sustained immunovirological control for more than 6 years of treatment discontinuation. 2 conditions: Treat early (median 2.3 weeks) Treat for long (median 5 years)

13 HAART Circulating virus Circulating virus Time HAART

14 Rafick Sekaly: Mechanisms of HIV persistence
Viral replication T cell survival Proliferation

15 Targeting the latent reservoir Suberoylanilide hydroxamic acid
SAHA CD4 TCM cell survival Histone deacetylase inhibitors Suberoylanilide hydroxamic acid D. Margolis, D. Hazuda, C. VanLint, A. Savarino

16 Targeting the cells: A role for PD-1 in HIV latency
p24 (pg/ml) Time (d) CD3/CD28 + IgG2 CD3/CD28 + PD-L1 NS The negative signal conferred by the PD-1/PD-L1 interaction inhibits viral production in primary CD4+T cells from viremic donors PD-1 expression correlates with the reservoir size

17 Targeting the proliferative reservoir
IL-15 CD4 T cell homeostatic proliferation IL-7 IL-7: Necessary for homeostatic renewal IL-15: Prompts cell maturation and viral replication

18 Boosting immune responses: Vaccines
Correlates of control T cells predict control (but not protection, Gary Nabel) The magnitude and function of CD8 T cells are associated with control of the viral reservoir (Brigitte Autran). NK cells (and their KIR receptors) are associated with viral control (Marcus Altfeld)

19 Interventions for HIV Cure
Reduce residual replication/production: Optimize HAART (J. Martinez Picado, Stefano Vella) Intensification Drug penetration Reduce immune activation (Steve Deeks) Anti-inflammatory drugs Reduce gut damage and /or microbial translocation Anti CMV drugs Target latent reservoirs IL-7 (Eramune) or anti IL-7 HDAC Anti PD-1 Gene Therapy (Jan Van Lunzen) Immune control of reservoirs (Brigitte Autran) IL-7 HIV-specific IgG2 are associated with control in LTNP NK cells C U R E

Download ppt "New concepts in HIV: HIV immunopathogenesis, treatment and vaccine strategies - report back from pre-conference Nicolas Chomont VGTI-Florida."

Similar presentations

Hopital Pitié Salpérière

Hopital Pitié Salpérière
Effect of intensification of long-term highly active antiretroviral therapy (HAART) with raltegravir on proviral HIV-1 DNA in blood and gut associated.

Effect of intensification of long-term highly active antiretroviral therapy (HAART) with raltegravir on proviral HIV-1 DNA in blood and gut associated.
ARV overview and toxicity Dr Francois Venter Reproductive Health Research Unit University of the Witwatersrand.

ARV overview and toxicity Dr Francois Venter Reproductive Health Research Unit University of the Witwatersrand.
Emerging patterns of drug resistance and viral tropism in cART-naïve and failing patients infected with HIV-1 subtype C Thumbi Ndung’u, BVM, PhD Associate.

Emerging patterns of drug resistance and viral tropism in cART-naïve and failing patients infected with HIV-1 subtype C Thumbi Ndung’u, BVM, PhD Associate.
Purging the HIV-1 Reservoir Through the Disruption of the PD-1 Pathway

Purging the HIV-1 Reservoir Through the Disruption of the PD-1 Pathway
Measuring the latent HIV Reservoir

Measuring the latent HIV Reservoir
Contribution of the immune system to HIV persistence Sharon R Lewin Director, Infectious Disease Unit, Alfred Hospital Professor, Department of Medicine,

Contribution of the immune system to HIV persistence Sharon R Lewin Director, Infectious Disease Unit, Alfred Hospital Professor, Department of Medicine,
S Collins, I-Base: Introduction to cure researchUK-CAB January 2013 HIV cure research: pieces in the puzzle Simon Collins HIV i-Base.

S Collins, I-Base: Introduction to cure researchUK-CAB January 2013 HIV cure research: pieces in the puzzle Simon Collins HIV i-Base.
Interactive Workshop “HIV Cure 101”: Challenges in identifying and targeting the HIV reservoir Sarah Palmer Centre for Virus Research Westmead Millennium.

Interactive Workshop “HIV Cure 101”: Challenges in identifying and targeting the HIV reservoir Sarah Palmer Centre for Virus Research Westmead Millennium.
Www.ias2011.org Evaluating residual HIV reservoirs Background or why is this important? What can be measured? Where should we measure it? Conclusions.

Evaluating residual HIV reservoirs Background or why is this important? What can be measured? Where should we measure it? Conclusions.
Main questions on HIV persistence and on obstacles to HIV eradication Jean-Pierre Routy M.D. McGill University Montreal Toward an HIV cure: Insight into.

Main questions on HIV persistence and on obstacles to HIV eradication Jean-Pierre Routy M.D. McGill University Montreal Toward an HIV cure: Insight into.
Controversies in HIV Cure Research 18.3 0 Debate 1. Is there ongoing replication under HAART? Mario Stevenson and Frank Maldarelli Moderator: Steve Deeks.

Controversies in HIV Cure Research Debate 1. Is there ongoing replication under HAART? Mario Stevenson and Frank Maldarelli Moderator: Steve Deeks.
1 HIV Curative Strategies: Key Research Priorities Deeks S, et al., (2013) Nat Rev Immunol. 12(8): 607-614.

1 HIV Curative Strategies: Key Research Priorities Deeks S, et al., (2013) Nat Rev Immunol. 12(8):
Over 50 million HIV/AIDS cases have occurred worldwide Over 40 million people are currently living with HIV/AIDS 95% of all cases are in developing countries.

Over 50 million HIV/AIDS cases have occurred worldwide Over 40 million people are currently living with HIV/AIDS 95% of all cases are in developing countries.
Cost-effectiveness of different starting criteria of antiretroviral therapy in Mexico. Caro Y., Colchero A., Valencia A., Bautista-Arredondo S., Sierra.

Cost-effectiveness of different starting criteria of antiretroviral therapy in Mexico. Caro Y., Colchero A., Valencia A., Bautista-Arredondo S., Sierra.
2014 “Towards an HIV Cure” symposium Melbourne A novel assay that precisely measures the size of the latent HIV reservoir reveals that ART-nai ̈ ve individuals.

2014 “Towards an HIV Cure” symposium Melbourne A novel assay that precisely measures the size of the latent HIV reservoir reveals that ART-nai ̈ ve individuals.
Current HIV basic science research topics. Toddler Functionally Cured of HIV Infection- “the Mississippi Baby” First well-documented case of an HIV.

Current HIV basic science research topics. Toddler "Functionally Cured" of HIV Infection- “the Mississippi Baby” First well-documented case of an HIV.
Strategies for Targeting and Eradicating the HIV Reservoir

Strategies for Targeting and Eradicating the HIV Reservoir
Hematopoietic stem cell based gene therapy for HIV diseases

Hematopoietic stem cell based gene therapy for HIV diseases
David M. Margolis, MD Professor of Medicine Towards an HIV cure: medical, social and ethical challenges in research and testing.

David M. Margolis, MD Professor of Medicine Towards an HIV cure: medical, social and ethical challenges in research and testing.

Similar presentations

Ads by Google