Establishment and Targeting of the Viral Reservoir in Rhesus Monkeys
|
|
- Felicia Douglas
- 6 years ago
- Views:
Transcription
1 Establishment and Targeting of the Viral Reservoir in Rhesus Monkeys Dan H. Barouch, M.D., Ph.D. Center for Virology and Vaccine Research Beth Israel Deaconess Medical Center Ragon Institute of MGH, MIT, and Harvard August 8, 2014
2 Early Treatment of Acute SIVmac251 Infection in Rhesus Monkeys The latent viral reservoir that persists despite ART represents the most critical challenge facing HIV-1 eradication strategies Early ART has been shown to reduce the size of the reservoir in certain HIV-1-infected humans However, it remains unclear precisely when and where the reservoir is established, although it is believed to be seeded in acute HIV-1 infection during peak viremia We therefore investigated the impact of early ART on viral reservoirs in acute SIV infection in rhesus monkeys
3 Study Design IR SIVmac251 infection in 20 rhesus monkeys ART initiated on day 3, 7, 10, 14, or no ART (N=4/group) Gilead ART cocktail (tenofovir, emtricitabine, dolutegravir) Daily ART x 24 weeks followed by treatment discontinuation BIDMC, Ragon Institute, Harvard, MHRP, Gilead, Bioqual
4 SIVmac251 Infection No ART Log SIV RNA Copies / ml Days Following SIV Infection
5 SIVmac251 Infection ART Started Day 14 Log SIV RNA Copies / ml Days Following SIV Infection
6 SIVmac251 Infection ART Started Day 10 Log SIV RNA Copies / ml Days Following SIV Infection
7 SIVmac251 Infection ART Started Day 7 Log SIV RNA Copies / ml Days Following SIV Infection
8 SIVmac251 Infection ART Started Day 3 Log SIV RNA Copies / ml Days Following SIV Infection
9 No SIV Env ELISA Responses with Day 3 ART Reduced SIV Env ELISA Responses with Day 7-14 ART week
10 No SIV ELISPOT Responses with Day 3 ART Reduced SIV ELISPOT Responses with Day 7-14 ART week
11 Proviral DNA Detected in Lymph Nodes and Gut Mucosa but not in PBMC with Day 3 ART Log DNA Copies / 10 6 Cells PBMC LNMC GMMC Days Following SIV Infection
12 Proviral DNA Detected in PBMC, Lymph Nodes, and Gut Mucosa with Day 7 ART Log DNA Copies / 10 6 Cells PBMC LNMC GMMC Days Following SIV Infection
13 Proviral DNA Detected in PBMC, Lymph Nodes, and Gut Mucosa with Day 10 ART Log DNA Copies / 10 6 Cells PBMC LNMC GMMC Days Following SIV Infection
14 Proviral DNA Detected in PBMC, Lymph Nodes, and Gut Mucosa with Day 14 ART Log DNA Copies / 10 6 Cells PBMC LNMC GMMC Days Following SIV Infection
15 Early ART Reduces the Size of Viral Reservoirs PBMC LNMC GMMC P< P< P< P=0.004 P=NS Day of ART Initiation Day of ART Initiation Day of ART Initiation
16 SIV DNA / 10 6 CD4 T C e lls Proviral DNA is First Detected in Transitional and Central Memory CD4+ T Cells in Lymph Nodes Day 3 Day N T M C M 0 0 G e n ita l Ilia c Mesenteric PBMC G e n ita l Ilia c A x illa ry Mesenteric PBMC 1000 Lym ph Node Lym ph Node SIV DNA / 10 6 CD4 T C e lls G e n ita l Inguinal Ilia c P ara PBMC G e n ita l Inguinal Ilia c P ara A x illa ry Mesenteric PBMC Lym ph Node Lym ph Node
17 SIVmac251 Infection ART Started Day 3 No Plasma Virus (<50 Copies/ml) for 24 Weeks Log SIV RNA Copies / ml ART Days Following SIV Infection
18 SIVmac251 Infection ART Started Day 3 Viral Rebound in 100% of Animals After Stopping ART ART Stopped Log SIV RNA Copies / ml ART Days Following SIV Infection
19 Day 3 Delayed Viral Rebound in Monkeys Started on ART on Day 3 vs. Days 7-14 Log SIV RNA Copies / ml Day 7 Day 10 Day 14 Days Following SIV Infection
20 Delayed Viral Rebound in Monkeys Started on ART on Day 3 vs. Days 7-14 Days to Viral Rebound P= Day 3 Day 7 Day 10 Day 14
21 ART Regimen Completely Suppressed Viral Replication at Week 20 (<6 Copies/ml) Log SIV RNA Copies / m l D a y 3 D a y 7 Day 10 Day 14 < 6 copies/ml Day of ART Initiation
22 Pre-ART Viremia During Acute Infection Predicts the Size of the Viral Reservoir Log PBMC DNA y = 0.43x 0.70 R 2 = 0.81 P< Log LNMC DNA y = 0.32x 0.25 R 2 = 0.45 P= Log Pre-ART AUC VL Log Pre-ART AUC VL
23 Pre-ART Viremia and Size of the Viral Reservoir Predict Time to Viral Rebound Days to Viral Rebound y = -2.7 x R 2 = 0.71 P< Days to Viral Rebound y = -7.3 x R 2 = 0.48 P= Log Pre-ART AUC VL Log PBMC DNA
24 Conclusions (I) Viral reservoir in this model was established remarkably early: within 3 days of infection, during the eclipse period of infection, and prior to plasma viremia ( Fiebig 0 ) In the first few days after IR SIV infection, reservoir was rapidly established in lymph nodes and/or gut mucosa before PBMC Early ART on day 3 reduced the size of the viral reservoir and delayed viral rebound, but this did not prevent viral rebound This very early establishment of the viral reservoir poses new challenges for HIV-1 cure strategies and suggests potential limitations of early ART strategies
25 Nature /13594 July 20 (2014)
26 Nature /13647 July 20 (2014)
27 Can Potent Neutralizing HIV-1-Specific Monoclonal Antibodies Contribute to HIV-1 Eradication Efforts?
28 Therapeutic Efficacy of Potent Neutralizing HIV-1- Specific Monoclonal Antibodies Current neutralizing HIV-1-specific mabs are substantially more potent and broad than those available previously The broad and potent glycan-dependent and CD4 binding site-specific mabs have been shown to block SHIV acquisition in passive protection studies in rhesus monkeys We and others have recently demonstrated the therapeutic efficacy of potent neutralizing HIV-1-specific mabs in chronically SHIV-infected rhesus monkeys Collaboration with Michel Nussenzweig and Dennis Burton Barouch et al. Nature 2013; 503: Shingai et al. Nature 2013; 503:277
29 Barouch et al. Nature 2013; 503:
30 Summary of Therapeutic Efficacy of PGT121 or PGT121-Containing mab Cocktails
31 A Single N332 Mutation Does Not Fully Abrogate PGT121 Activity: Intrinsic High Bar to Resistance? PGT121 makes at least 4 glycan contacts at N332, N301, N156/173, N137 (Burton, Wilson)
32 Decline of Proviral DNA in Lymph Nodes, GI Mucosa, and PBMC Following a Single Infusion of PGT121 P = 0.05 P = 0.1 P = 0.05
33 Picker and Deeks Nature 2013; 503: Weiss NEJM 2014; 370:
34 Potential Role of Broadly Neutralizing mabs in HIV-1 Eradication Strategies? Our published studies demonstrated that PGT121 reduced proviral DNA in tissues in viremic monkeys, but did not assess if PGT121 can target the reservoir in ART-suppressed animals Clinical studies are planned to assess whether broadly neutralizing mabs can reduce proviral DNA in ART-suppressed, HIV-1-infected humans A key question is whether reservoir cells express sufficient Env to be targeted by mabs (i.e. homeostatic proliferation, low levels of virus production, immune or pharmacologic activation, etc.) We therefore performed a pilot study to evaluate the impact of PGT121 in ART-suppressed, SHIV-infected rhesus monkeys
35 Therapeutic Efficacy of PGT121 in ART-Suppressed, SHIV-Infected Rhesus Monkeys 9 rhesus monkeys infected with SHIV-SF162P3 for 7 months; baseline viral loads log RNA copies/ml Daily suppressive ART initiated in all animals and continued for 20 weeks (tenofovir, emtricitabine, dolutegravir) Group 1 (N=5): ART (weeks 0-20) + PGT121 (weeks 0, 4, 8, 12) Group 2 (N=4): ART (weeks 0-20) alone ART discontinued at week 20
36 Rapid and Complete Virologic Suppression Following Initiation of Both ART + PGT121 and ART Alone ART + PGT121 ART Alone PGT121 ART ART Log RNA Copies/ml Days Following Study Initiation
37 Reduction in Proviral DNA in PBMC in ART + PGT121 Treated Rhesus Monkeys ART + PGT121 ART Alone Log DNA Copies/10 6 PBMC Days Following Study Initiation
38 Reduction in Proviral DNA in Gastrointestinal Mucosa in ART + PGT121 Treated Rhesus Monkeys ART + PGT121 ART Alone Log DNA Copies/10 6 GMMC Days Following Study Initiation
39 Rapid and Complete Virologic Suppression Following Initiation of Both ART + PGT121 and ART Alone ART + PGT121 ART Alone PGT121 ART ART Log RNA Copies/ml Days Following Study Initiation
40 Partial Virologic Control in ART + PGT121 Treated Monkeys Following ART Discontinuation ART + PGT121 ART Alone PGT121 ART ART Log RNA Copies/ml Days Following Study Initiation 60% (3 of 5) Virologic Control 0% (0 of 4) Virologic Control
41 Conclusions (II) In a pilot study, PGT121 reduced proviral DNA in PBMC and tissues in ART-suppressed, SHIV-infected rhesus monkeys ART + PGT121 resulted in virologic control in 60% (3 of 5) of animals following ART discontinuation Larger, definitive NHP studies will be needed to confirm and extend these results and guide clinical development strategies PGT121, both alone and in combination with other mabs, should be evaluated in humans as part of HIV-1 eradication strategies PGT121 GMP manufacturing in progress; clinical studies in HIV- 1-infected humans scheduled to begin in 2015
42 Acknowledgements (Early ART Studies) Beth Israel Deaconess, Harvard Medical School James Whitney Pablo Penaloza Jennifer Shields Lily Parenteau Jinyan Liu Kaitlin Smith Erica Borducchi Crystal Cabral Jeffrey Smith Stephen Blackmore Srisowmya Sanisetty Harvard University Alison Hill Daniel Rosenbloom Martin Nowak Gilead Romas Geleziunas Bioqual Mark Lewis MHRP Nelson Michael Jerome Kim Merlin Robb Ragon Institute of MGH, MIT, and Harvard DAIDS, NIAID, NIH Michael Pensiero
43 Acknowledgements (Therapeutic mab Studies) Beth Israel Deaconess, Harvard Medical School James Whitney Jinyan Liu Kathryn Stephenson Hui-Wen Chang Joseph Nkolola Michael Seaman Kaitlin Smith Erica Borducchi Crystal Cabral Jeffrey Smith Stephen Blackmore Srisowmya Sanisetty James Perry Rockefeller University Florian Klein Thiago Oliveira Michel Nussenzweig Scripps Brian Moldt Pascal Poignard Dennis Burton Bioqual Mark Lewis Catalent Pharma Theraclone Sciences Kristine Swiderek Gilead Sciences Romas Geleziunas Ragon Institute of MGH, MIT, and Harvard DAIDS, NIAID, NIH Michael Pensiero Gates Foundation Pervin Anklesaria Nina Russell
Rapid Seeding of the Viral Reservoir Prior to SIV Viremia in Rhesus Monkeys
Rapid Seeding of the Viral Reservoir Prior to SIV Viremia in Rhesus Monkeys The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters.
More informationTherapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys
Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys The MIT Faculty has made this article openly available. Please share how this access benefits
More informationNovel Heterologous Prime-Boost Vaccine Strategies for HIV. Dan Barouch April 18, 2012
Novel Heterologous Prime-Boost Vaccine Strategies for HIV Dan Barouch April 18, 2012 Desired Features of a Next Generation HIV-1 Vaccine Candidate The RV1 study suggests that an HIV-1 vaccine is possible
More informationMHRP. Outline. Is HIV cure possible? HIV persistence. Cure Strategies. Ethical and social considerations. Short video on patients perspectives on cure
Outline Is HIV cure possible? Ø HIV persistence Cure Strategies Ethical and social considerations Short video on patients perspectives on cure A Case of Cure Off ART Treatment Mechanism Lesson The Berlin
More informationHIV cure: current status and implications for the future
HIV cure: current status and implications for the future Carolyn Williamson, PhD Head of Medical Virology, Faculty Health Sciences, University of Cape Town CAPRISA Research Associate, Centre of Excellence
More informationState of the ART: HIV Cure where are we now and. where are we going? Jintanat Ananworanich, MD, PhD MHRP
State of the ART: HIV Cure where are we now and ì where are we going? Jintanat Ananworanich, MD, PhD Associate Director for Therapeu1cs Research US Military HIV Research Program (MHRP) Maryland, USA Deputy
More informationThe potential role of PD-1/PD-L1 blockade in HIV Remission and Cure Strategies
The potential role of PD-1/PD-L1 blockade in HIV Remission and Cure Strategies Stephen Mason Director, Discovery Virology Bristol-Myers Squibb Community Cure Workshop 2015 Sunday, Feb 22, 2015 Seattle,
More informationAntibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys
Corrected: Publisher Correction https://doi.org/1.18/s18-18-- Antibody and TLR agonist delay viral rebound in SHIV-infected monkeys Erica N. Borducchi 1,, Jinyan Liu 1,, Joseph P. Nkolola 1,, Anthony M.
More informationBroadly Neutralizing Antibodies for HIV Eradication
DOI 10.1007/s11904-016-0299-7 HIV PATHOGENESIS AND TREATMENT (AL LANDAY, SECTION EDITOR) Broadly Neutralizing Antibodies for HIV Eradication Kathryn E. Stephenson 1,2 & Dan H. Barouch 1,2 # The Author(s)
More informationPreclinical Animal Models for HIV Cure Research in Children: Scientific Knowledge Gaps
Preclinical Animal Models for HIV Cure Research in Children: Scientific Knowledge Gaps NIAID Workshop, May 22-23, 2018 Nancy L. Haigwood, Oregon Health & Science University Mississippi baby case brought
More informationApproaching a Cure Daniel R. Kuritzkes, MD
Approaching a Cure Daniel R. Kuritzkes, MD Division of Infectious Diseases Brigham and Women s Hospital Harvard Medical School Disclosures The speaker is a consultant and/or has received speaking honoraria
More informationViral Reservoirs and anti-latency interventions in nonhuman primate models of SIV/SHIV infection
Viral Reservoirs and anti-latency interventions in nonhuman primate models of SIV/SHIV infection Koen Van Rompay California National Primate Research Center University of California Davis Outline Introduction
More informationDr Jintanat Ananworanich
BHIVA AUTUMN CONFERENCE 2014 Including CHIVA Parallel Sessions Dr Jintanat Ananworanich US Military HIV Research Program in Bethesda Maryland, USA 9-10 October 2014, Queen Elizabeth II Conference Centre,
More informationAd26/MVA Therapeutic Vaccination with TLR7 Stimulation in SIV- Infected Rhesus Monkeys
Ad26/MVA Therapeutic Vaccination with TLR7 Stimulation in SIV- Infected Rhesus Monkeys The Harvard community has made this article openly available. Please share how this access benefits you. Your story
More informationNovel Approaches for the Assessment of the In Vivo Residual Virus Pool and Viral Eradication Strategies in SIV-infected Rhesus Macaques
Towards an HIV Cure Pre-Conference Symposium 20 & 21 July 2012 Novel Approaches for the Assessment of the In Vivo Residual Virus Pool and Viral Eradication Strategies in SIV-infected Rhesus Macaques Gregory
More informationA VACCINE FOR HIV BIOE 301 LECTURE 10 MITALI BANERJEE HAART
BIOE 301 LECTURE 10 MITALI BANERJEE A VACCINE FOR HIV HIV HAART Visit wikipedia.org and learn the mechanism of action of the five classes of antiretroviral drugs. (1) Reverse transcriptase inhibitors (RTIs)
More informationDual approach to HIV-1 cure: Activation of latency and restoration of exhausted virus-specific T cell function
Dual approach to HIV-1 cure: Activation of latency and restoration of exhausted virus-specific T cell function Stephen Mason Director, Discovery Virology Bristol-Myers Squibb Disclosure: Paid employee
More informationDEBATE ON HIV ENVELOPE AS A T CELL IMMUNOGEN HAS BEEN GAG-GED
DEBATE ON HIV ENVELOPE AS A T CELL IMMUNOGEN HAS BEEN GAG-GED Viv Peut Kent Laboratory, University of Melbourne, Australia WHY ENVELOPE? Env subject to both humoral and cellular immune responses Perhaps
More informationIdentification and Characterization of CD4 T cells actively transcribing HIV RNA in Peripheral Blood
Dale and Betty Bumpers Vaccine Research Center National Institute of Allergy and Infectious Diseases National Institutes of Health Identification and Characterization of CD4 T cells actively transcribing
More informationSupplementary Materials for
www.sciencetranslationalmedicine.org/cgi/content/full//49/eaao4/dc Supplementary Materials for TLR agonists induce transient viremia and reduce the viral reservoir in SIV-infected rhesus macaques on antiretroviral
More informationThe HIV Cure Agenda. CHIVA Oct Nigel Klein. Institute of Child Health and Great Ormond Street Hospital, London, UK
The HIV Cure Agenda CHIVA Oct 2016 Nigel Klein Institute of Child Health and Great Ormond Street Hospital, London, UK 2 How frequently is HIV cured? The Berlin patient Restriction of HIV entry CD4 is
More informationPrEP: Is Longer Better? Myron S. Cohen, MD
PrEP: Is Longer Better? Myron S. Cohen, MD Yeargan-Bate Eminent Professor Medicine, Microbiology and Epidemiology Director, Institute for Global Health & Infectious Diseases TDF/FTC was FDA Approved for
More informationHIV Antibody Characterization for Reservoir and Eradication Studies. Michael Busch, Sheila Keating, Chris Pilcher, Steve Deeks
HIV Antibody Characterization for Reservoir and Eradication Studies Michael Busch, Sheila Keating, Chris Pilcher, Steve Deeks Blood Systems Research Institute University of California San Francisco, CA
More informationPress conference abstracts Vaccine and Antibody Research Monday, 22 October 2018
Press conference abstracts Vaccine and Antibody Research Monday, 22 October 2018 OA02.05LB Vaccine-induced Gene Signature Correlates with Protection against Acquisition in Three Independent Vaccine Efficacy
More informationCROI 2016 Review: Immunology and Vaccines
Frontier AIDS Education and Training Center CROI 2016 Review: Immunology and Vaccines Meena Ramchandani MD MPH Acting Instructor, University of Washington March 2016 This presentation is intended for educational
More informationInnovative diagnostics for HIV, HBV and HCV
Innovative diagnostics for HIV, HBV and HCV Dan Otelea National Institute for Infectious Diseases Bucharest, Romania Disclaimer No conflicts of interest Innovative diagnostics for HIV, HBV and HCV - is
More informationProfessor Jonathan Weber
HIV/AIDS at 30: Back to the Future BHIVA / Wellcome Trust Multidisciplinary Event to mark World AIDS Day 2011 British HIV Association (BHIVA) 2011 HIV/AIDS at 30: Back to the Future BHIVA / Wellcome Trust
More informationWhat is the place of the monoclonal antibodies in the clinic?
What is the place of the monoclonal antibodies in the clinic? Dr Julià Blanco 2018/04/26 DISCLOSURE AlbaJuna Therapeutics, S.L. ANTIBODIES IN HIV INFECTION. ANTIVIRAL (NEUTRALIZING) ACTIVITY env THE BROADLY
More informationWith over 20 drugs and several viable regimens, the mo6vated pa6ent with life- long access to therapy can control HIV indefinitely, elimina6ng the
Towards an HIV Cure Steven G. Deeks, MD Professor of Medicine in Residence HIV/AIDS Division University of California, San Francisco (UCSF) WorldMedSchool; July 22, 2013 1 With over 20 drugs and several
More informationTowards an HIV Cure. Steven G. Deeks Professor of Medicine University of California, San Francisco
Towards an HIV Cure Steven G. Deeks Professor of Medicine University of California, San Francisco Why are we now talking about a cure? Emerging recognition that HAART does not fully restore health and/or
More informationRoger Shapiro, MD, MPH Harvard TH Chan School of Public Health Botswana-Harvard Partnership May 2018
A Clinical Trial to Evaluate the Impact of Broadly Neutralizing Antibodies VRC01LS and 10-1074 on Maintenance of HIV Suppression in a Cohort of Early-Treated Children in Botswana Roger Shapiro, MD, MPH
More informationT Memory Stem Cells: A Long-term Reservoir for HIV-1
Towards an HIV Cure Pre-Conference Symposium 20 & 21 July 2012 T Memory Stem Cells: A Long-term Reservoir for HIV-1 Maria J Buzon, PhD Ragon Institute of MGH, MIT and Harvard, Massachussetts General Hospital,
More informationWorking Group#1: Trial Endpoints, Biomarkers & Definitions
Working Group#1: Trial Endpoints, Biomarkers & Definitions Forum HIV Cure Project: Focus on The Regulatory Pathway June 17, 2014 www.hivforum.org Comments from co-chairs john mellors and mike miller www.hivforum.org
More informationThe Harvard community has made this article openly available. Please share how this access benefits you. Your story matters
Antibody Responses After Analytic Treatment Interruption in Human Immunodeficiency Virus-1- Infected Individuals on Early Initiated Antiretroviral Therapy The Harvard community has made this article openly
More informationSupporting Information
Supporting Information Horwitz et al. 73/pnas.35295 A Copies ml - C 3NC7 7 697 698 7 7 73 76-2 2 Days Gp2 residue G458D G459D T278A 7/36 N28 K D 28 459 A28T ID# 697 ID# 698 ID# 7 ID# 7 ID# 73 ID# 76 ID#
More informationPediatric HIV Cure Research
Pediatric HIV Cure Research HIV Cure Research Training Curriculum Pediatric HIV Cure Research Presented by: Priyanka Uprety,MSPH, PhD Laboratory of Deborah Persaud, MD Johns Hopkins University July 2016
More informationThe Kitchen Sink. Glenda Gray AIDS vaccine at the cross roads: how to adapt to a new preven9on age? Monday 7 th October, 2013, Barcelona
The Kitchen Sink Glenda Gray AIDS vaccine at the cross roads: how to adapt to a new preven9on age? Monday 7 th October, 2013, Barcelona The only important slide of my presentation. All efficacy trial in
More informationNature Medicine: doi: /nm.4411
Supplementary Figure 1. Plasma viral load decay characteristics in each of 4 monkey cohorts studied after prolonged ART. A. Decay in 5 SIV infected animals treated ART for 20-22 weeks. B, C. Decay in additional
More informationA Quarterly Update on HIV Prevention Research. Vol. 8 No. 2
A Quarterly Update on HIV Prevention Research Vol. 8 No. 2 April June 2015 What is it? What could it do? Key Facts Antibodies Passive immunization is the transfer of pre-made antibodies to a person. Passive
More informationCombined IL-21 and IFNα treatment limits inflammation and delay viral rebound in ART-treated, SIV-infected macaques
Combined and IFNα treatment limits inflammation and delay viral rebound in ART-treated, SIV-infected macaques Mirko Paiardini Associate Professor, Emory University School of Medicine Yerkes National Primate
More informationHIV vaccines, neutralising antibodies, ADCC and beyond. Stephen Kent University of Melbourne Peter Doherty Institute
HIV vaccines, neutralising antibodies, ADCC and beyond Stephen Kent University of Melbourne Peter Doherty Institute Viro-Immunobabble bingo Virology/Immunology/vaccinology full of jargon! Shout Immunobabble
More informationTherapeutic DNA Vaccine Induces Broad T Cell Responses in the Gut and Sustained Protection from Viral Rebound and AIDS in SIV-Infected Rhesus Macaques
Therapeutic DNA Vaccine Induces Broad T Cell Responses in the Gut and Sustained Protection from Viral Rebound and AIDS in SIV-Infected Rhesus Macaques Deborah Heydenburg Fuller 1,2,3 * a, Premeela Rajakumar
More informationCure: Early Detection and Early Treatment"
Cure: Early Detection and Early Treatment" ECHO (RV217) and RV 254 Merlin L. Robb, MD, Dr. Jintanat Ananworanich, and Dr. Jerome Kim and Dr. Nelson Michael 4 th International Workshop on HIV & Women 13-14
More informationEarly Antiretroviral Therapy
Early Antiretroviral Therapy HIV Cure Research Training Curriculum HIV and Cure Early ART Presented by: Jintanat Ananworanich, MD, PhD June 2016 The HIV CURE research training curriculum is a collaborative
More informationPredicting treatment outcomes using rich adherence data & antiretroviral pharmacometrics
Predicting treatment outcomes using rich adherence data & antiretroviral pharmacometrics Daniel Scholes Rosenbloom, Alison L. Hill, Robert F. Siliciano, Martin A. Nowak, Carol Golin, Robert Remien, Ira
More informationInves)gación básica y curación del VIH- 1
Inves)gación básica y curación del VIH- 1 Javier Mar)nez- Picado (jmpicado@irsicaixa.es) 23 rd Conference on Retroviruses and Opportunis5c Infec5ons February 22-25, 2016 Boston, Massachuse8s UNIVERSITAT
More informationUnderstanding HIV. Transmitted/Founder Viruses. Brandon Keele SAIC-Frederick National Cancer Institute
Understanding HIV Transmission Utilizing Transmitted/Founder Viruses Brandon Keele SAIC-Frederick National Cancer Institute AIDS Vaccine 2011 15 September 2011 Overview Several years ago, the CHAVI sought
More informationHIV remission after discontinuing ART: is it achievable?
HIV remission after discontinuing ART: is it achievable? Jintanat Ananworanich, MD, PhD Associate Director for Therapeutics Research US Military HIV Research Program Maryland, USA jananworanich@hivresearch.org
More informationShould There be Further Efficacy Testing of T-T cell Based Vaccines that do not Induce Broadly Neutralizing Antibodies?
Dale and Betty Bumpers Vaccine Research Center National Institute of Allergy and Infectious Diseases National Institutes of Health Department of Health and Human Services Should There be Further Efficacy
More informationHIV and Challenges of Vaccine Development
Dale and Betty Bumpers Vaccine Research Center National Institute of Allergy and Infectious Diseases National Institutes of Health HIV and Challenges of Vaccine Development Richard A. Koup, MD INTEREST
More informationInvited Review CROI 2018: Advances in Basic Science Understanding of HIV
Invited Review CROI 2018: Advances in Basic Science Understanding of HIV Mario Stevenson, PhD The conference on Retroviruses and Opportunistic Infections represents the most important venue for the dissemination
More informationAlternate Antibody-Based Therapeutic Strategies To Purge the HIV Cell Reservoir
Alternate Antibody-Based Therapeutic Strategies To Purge the HIV Cell Reservoir Giuseppe Pantaleo, M.D. Professor of Medicine Head, Division of Immunology and Allergy Executive Director, Swiss Vaccine
More informationLow-Level Viremia in HIV
Mountain West AIDS Education and Training Center Low-Level Viremia in HIV Brian R. Wood, MD Medical Director, Mountain West AETC ECHO Telehealth Program Assistant Professor of Medicine, University of Washington
More informationThe Impact of Immunoglobulin in Acute HIV Infection on the HIV Reservoir: A Pilot Randomized Controlled Trial
The Impact of Immunoglobulin in Acute HIV Infection on the HIV Reservoir: A Pilot Randomized Controlled Trial Olubanke Davies Guy s & St Thomas NHS Foundation Trust BACKGROUND Immediate ART during acute
More informationThe Collaboration for AIDS Vaccine Discovery. 10th Annual Meeting. Grantee Profiles. December 7 9, 2015 Seattle, Washington
The Collaboration for AIDS Vaccine Discovery 10th Annual Meeting Profiles December 7 9, 2015 Seattle, Washington Table of Contents Ackerman/Alter: Leveraging Antibody Effector Function 4 Alter: A Genetic
More informationSetting the Stage: Long-acting agents for PrEP
Setting the Stage: Long-acting agents for PrEP Martin Markowitz MD Aaron Diamond AIDS Research Center Rockefeller University May 6, 2013 Setting the Stage Results of PrEP studies - Focus on adherence Long-acting
More informationLynn Morris. "Plan B"- bnabs for HIV prevention
"Plan B"- bnabs for HIV prevention Lynn Morris National Institute for Communicable Diseases, a division of the National Health Laboratory Service (NHLS) of South Africa, University of the Witwatersrand,
More informationMacmillan Publishers Limited. All rights reserved
LETTER doi:0.038/nature2746 Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia Masashi Shingai *, Yoshiaki Nishimura *, Florian Klein 2, Hugo Mouquet 3, Olivia
More informationBispecific Fusion Antibodies. Exhibit 100% Breadth and Picomolar Potency. Craig Pace, PhD
The Aaron Diamond AIDS Research Center Affiliate of The Rockefeller University Bispecific Fusion Antibodies PG9 Ibalizumab & VRC Ibalizumab Exhibit % Breadth and Picomolar Potency Craig Pace, PhD AIDS
More informationHIV Basics: Pathogenesis
HIV Basics: Pathogenesis Michael Saag, MD, FIDSA University of Alabama, Birmingham Director, Center for AIDS Research ACTHIV 2011: A State-of-the-Science Conference for Frontline Health Professionals Learning
More informationInves&gación básica y curación del VIH-1
Inves&gación básica y curación del VIH-1 Javier Mar&nez-Picado 24 th Conference on Retroviruses and Opportunis6c Infec6ons UNIVERSITAT DE VIC Empezamos bien cart: How Early is Early Enough? Sáez-Cirion
More informationBEAT-HIV Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy
BEAT-HIV Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy We are pleased to announce that the National Institutes of Health (NIH) has awarded nearly $23 million to co-principal
More informationClinical Development of ABX464, drug candidate for HIV Functional Cure. Chief Medical Officer ABIVAX
Clinical Development of ABX464, drug candidate for HIV Functional Cure Jean-Marc Steens, MD Chief Medical Officer ABIVAX 1 DECLARATION OF CONFLICT OF INTEREST GSK ABIVAX 2 ABX464: Mechanism of Action ABX464
More informationTreatment of HIV-1 in Adults and Adolescents: Part 2
Treatment of HIV-1 in Adults and Adolescents: Part 2 Heather E. Vezina, Pharm.D. University of Minnesota Laboratory Medicine & Pathology Experimental & Clinical Pharmacology wynnx004@umn.edu Management
More informationNovel Vaccine Products for Planned Phase I Immunogenicity Studies in Infants
Office of AIDS Research Novel Vaccine Products for Planned Phase I Immunogenicity Studies in Infants L. Jean Patterson, PhD Office of AIDS Research, NIH February 7, 2017 Office of AIDS Research OAR Responsibilities
More informationCorrelates of Immunity: RV144 - Lessons Learned
Correlates of Immunity: RV144 - Lessons Learned US Military HIV Research Program (MHRP) Nelson L. Michael, MD, PhD AIDS Vaccine 2010, Atlanta GA 01 October 2010 Outline RV 144 Correlates Discovery Towards
More informationHIV remission: viral suppression in the absence of ART. Sarah Fidler Brian Gazzard Lecture BHIVA 2016
HIV remission: viral suppression in the absence of ART Sarah Fidler Brian Gazzard Lecture BHIVA 2016 Disclosures: My institution receives funding for research from MSD, GSK, ViiV, Gilead Summary of talk
More informationHIV/AIDS: vaccines and alternate strategies for treatment and prevention
Ann. N.Y. Acad. Sci. ISSN 0077-8923 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Online Meeting Report HIV/AIDS: vaccines and alternate strategies for treatment and prevention Yegor Voronin 1 and Sanjay
More informationTrials & Tribulations: on the way to cure: where do HIV Vaccines fit in? Glenda Gray SA HIV Clinicians Society Conference April, 2016
Trials & Tribulations: on the way to cure: where do HIV Vaccines fit in? Glenda Gray SA HIV Clinicians Society Conference 2016 13-16 April, 2016 Scope Rationale for an HIV vaccine RV144 study in Thailand
More informationLong-acting Antivirals Where Are We Headed? Are We Ready? Carl W. Dieffenbach, Ph.D. Director Division of AIDS, NIAID May 3, 2018
Long-acting Antivirals Where Are We Headed? Are We Ready? Carl W. Dieffenbach, Ph.D. Director Division of AIDS, NIAID May 3, 2018 Global HIV Statistics 2017 People living with HIV in 2016 New HIV infections
More informationCTLA-4-expressing CD4 T cells are critical contributors to SIV viral persistence
IAS 2015 Towards an HIV Cure symposium Vancouver CTLA-4-expressing CD4 T cells are critical contributors to SIV viral persistence Colleen McGary Paiardini lab Emory University HIV reservoir prevents eradication
More informationSupervised Treatment Interruption (STI) in an Urban HIV Clinical Practice: A Prospective Analysis.
Supervised Treatment Interruption (STI) in an Urban HIV Clinical Practice: A Prospective Analysis. J.L. YOZVIAK 1, P. KOUVATSOS 2, R.E. DOERFLER 3, W.C. WOODWARD 3 1 Philadelphia College of Osteopathic
More informationHIV viral load testing in the era of ART. Christian Noah Labor Lademannbogen, Hamburg
HIV viral load testing in the era of ART Christian Noah Labor Lademannbogen, Hamburg 1 Life expectancy of patients on ART Data from the UK Collaborative HIV Cohort (UK CHIC) Requirements: Early diagnosis
More informationDestruction of the Residual Active HIV-1 Reservoir by Env-specific Immunotoxin
Destruction of the Residual Active HIV-1 Reservoir by Env-specific Immunotoxin J. Victor Garcia-Martinez, Ph.D. University of North Carolina, at Chapel Hill IAS 2013 Towards an HIV Cure Symposium Delivering
More informationHIV Pathogenesis and Natural History. Peter W. Hunt, MD Associate Professor of Medicine University of California San Francisco
HIV Pathogenesis and Natural History Peter W. Hunt, MD Associate Professor of Medicine University of California San Francisco Learning Objectives Describe key features of HIV pathogenesis and natural history
More informationThe Genetic Barrier to Resistance
The Genetic Barrier to Resistance Jonathan M Schapiro, MD National Hemophilia Center, Israel Stanford University School of Medicine, USA Beijing, May 2013 The Genetic Barrier to Resistance The genetic
More informationPathogenesis Update Robert F. Siliciano, MD, PhD
Pathogenesis Update Robert F. Siliciano, MD, PhD Professor of Medicine and Molecular Biology and Genetics Johns Hopkins University School of Medicine Investigator, Howard Hughes Medical Institute HIV-1
More informationHIV cure strategies: interventions, endpoints and ethics
HIV cure strategies: interventions, endpoints and ethics Professor Sharon R Lewin, FRACP, PhD, FAHMS Fourth Joint Conference of BHIVA with BASSH, April 17-20, Edinburgh International Conference Centre,
More informationA Quarterly Update on HIV Prevention Research. Vol. 8 No. 2
What is it? What could it do? Key Facts Antibodies Passive immunization is the transfer of pre-made antibodies to a person. Passive immunization using today's pre-made antibodies can involve infusion delivered
More informationIAS 2016 Towards an HIV Cure Symposium Durban, South Africa.
Effect of vorinostat, hydroxychloroquine and maraviroc combination therapy on viremia following treatment interruption in individuals treated during acute HIV infection Eugène Kroon, Jintanat Ananworanich,
More informationPr Vincent Calvez. Faculté de Médecine Sorbonne Université UMR Sorbonne Université Inserm 1136 Service de Virologie Hôpital Pitié-Salpêtrière
Pr Vincent Calvez Faculté de Médecine Sorbonne Université UMR Sorbonne Université Inserm 1136 Service de Virologie Hôpital Pitié-Salpêtrière Pretreatment HIV Drug Resistance in the START Study Using Next
More informationWhat s New in Acute HIV Infection?
3 4 Disclosure I have received research grants awarded to my institution from Gilead Sciences, Inc. ntiretroviral medications have been provided by Gilead Sciences, Inc. Susan Little, M.D. Professor of
More informationIsolation of a Broadly Neutralizing Antibody with Low Somatic Mutation from a Chronically Infected HIV-1 Patient
Isolation of a Broadly Neutralizing Antibody with Low Somatic Mutation from a Chronically Infected HIV-1 Patient Amanda Fabra García, Carolina Beltrán Pavez, Alberto Merino Mansilla, Cristina Xufré, Isabel
More informationClinical Case. Prof.ssa Cristina Mussini
Clinical Case Prof.ssa Cristina Mussini Clinical history Male, born in Ivory Coast in 1968. HIV positive since dal 1998 Risk factor: heterosexual contacts He started antiretroviral therapy in 2001 with
More informationNIH Public Access Author Manuscript Nature. Author manuscript; available in PMC 2009 July 1.
NIH Public Access Author Manuscript Published in final edited form as: Nature. 2009 January 1; 457(7225): 87 91. doi:10.1038/nature07469. Immune Control of an SIV Challenge by a T Cell-Based Vaccine in
More informationProgress in HIV Vaccine Development Magdalena Sobieszczyk, MD, MPH. Division of Infectious Diseases Columbia University Medical Center
Progress in HIV Vaccine Development Magdalena Sobieszczyk, MD, MPH Division of Infectious Diseases Columbia University Medical Center 1 Outline A short history of HIV vaccine design and development Describe
More informationALVAC -HIV and AIDSVAX B/E Prime-Boost HIV-1 Preventive Vaccine Regimen. Results of the Thai HIV Vaccine Trial, RV144
ALVAC -HIV and AIDSVAX B/E Prime-Boost HIV-1 Preventive Vaccine Regimen Results of the Thai HIV Vaccine Trial, RV144 SupachaiRerks-Ngarm, PunneePittisutthithum, SorachaiNitayaphan, JaranitKaewkungwal,
More informationJournal of Infectious Diseases Advance Access published July 11, Effect of Antiretroviral Therapy on HIV Reservoirs in Elite Controllers
Journal of Infectious Diseases Advance Access published July 11, 2013 1 Effect of Antiretroviral Therapy on HIV Reservoirs in Elite Controllers Tae-Wook Chun 1,6, J. Shawn Justement 1, Danielle Murray
More informationModule R: Recording the HIV Reservoir
Module R: Recording the HIV Reservoir Satish K. Pillai, Ph.D. MODULE LEADER Satish Pillai amfar Institute for HIV Cure Research Module R Team Michael Busch Timothy Henrich Sheila Keating Sulggi Lee Henry
More informationcure research HIV & AIDS
Glossary of terms HIV & AIDS cure research Antiretroviral Therapy (ART) ART involves the use of several (usually a cocktail of three or more) antiretroviral drugs to halt HIV replication. ART drugs may
More informationHIV 101: Overview of the Physiologic Impact of HIV and Its Diagnosis Part 2: Immunologic Impact of HIV and its Effects on the Body
HIV 101: Overview of the Physiologic Impact of HIV and Its Diagnosis Part 2: Immunologic Impact of HIV and its Effects on the Body Melissa Badowski, PharmD, BCPS, AAHIVP Clinical Assistant Professor University
More informationEvaluation of lead HIV-1 vaccine regimen in APPROACH:
Evaluation of lead HIV-1 vaccine regimen in : Phase 1/2a study testing heterologous prime boost regimens using mosaic Ad26 and MVA vectors combined with Env protein Hanneke Schuitemaker Martin Freeman,
More informationSupplementary information. Early development of broad neutralizing antibodies in HIV-1 infected infants
Supplementary information Early development of broad neutralizing antibodies in HIV-1 infected infants Leslie Goo, Vrasha Chohan, Ruth Nduati, Julie Overbaugh Supplementary Figure 1. Neutralization profile
More informationNIH Public Access Author Manuscript J Acquir Immune Defic Syndr. Author manuscript; available in PMC 2013 September 01.
NIH Public Access Author Manuscript Published in final edited form as: J Acquir Immune Defic Syndr. 2012 September 1; 61(1): 19 22. doi:10.1097/qai.0b013e318264460f. Evaluation of HIV-1 Ambiguous Nucleotide
More informationInconsistent HIV reservoir dynamics and immune responses following anti-pd-1 therapy
Letter to Editor (Annals of Oncology): Inconsistent HIV reservoir dynamics and immune responses following anti-pd-1 therapy in cancer patients with HIV infection E. P. Scully 1,2,3, R. L. Rutishauser 4,
More informationHIV 101: Fundamentals of HIV Infection
HIV 101: Fundamentals of HIV Infection David H. Spach, MD Professor of Medicine University of Washington Seattle, Washington Learning Objectives After attending this presentation, learners will be able
More informationGLOBAL INVESTMENT IN HIV CURE RESEARCH AND DEVELOPMENT IN 2017 AFTER YEARS OF RAPID GROWTH FUNDING INCREASES SLOW
GLOBAL INVESTMENT IN HIV CURE RESEARCH AND DEVELOPMENT IN 2017 AFTER YEARS OF RAPID GROWTH FUNDING INCREASES SLOW TOWARDS AN CURE PEOPLE FOCUSED SCIENCE DRIVEN JULY 2018 A GLOBAL STRATEGIC APPROACH TOWARDS
More informationEradication of HIV infection Not in my lifetime? or Just around the Corner? Michael M. Lederman, MD
Eradication of HIV infection Not in my lifetime? or Just around the Corner? Michael M. Lederman, MD Conflicts of Interest The pending clinical trials discussed here are funded by grant awards from Gilead
More informationHIV/Sexual Health Clinical Education Session
HIV/Sexual Health Clinical Education Session http://courses.ashm.org.au/hiv/hiv-sexual-health-clinical-education-session/ About These Slide These slides may not be published, posted online, or used in
More informationRecent Insights into HIV Pathogenesis and Treatment: Towards a Cure
Recent Insights into HIV Pathogenesis and Treatment: Towards a Cure Deborah Persaud, M.D. Associate Professor Department of Pediatrics Division of Infectious Diseases Johns Hopkins University School of
More information