[CROI 2016] PROGRAMMA E ASPETTATIVE

[Dora]

Fra due settimane, fra il 22 e il 25 febbraio, si terrà il 23° CROI, che quest'anno torna a Boston.
Come sempre il programma definitivo non è ancora online, quindi per ora solo un rapido sguardo d'insieme. Appena avrò visto il programma completo segnalerò le cose che cercherò di seguire con più attenzione. Vale la solita premessa che non mi occuperò né di HIV nei bambini, né di HCV o tubercolosi o Ebola e che darò la precedenza agli studi sui farmaci e sulla cura di HIV e solo se ci saranno novità di grande rilievo scriverò qualcosa su temi di prevenzione.
Vi ricordo soltanto che, mentre noi siamo ancora qui a dover contrastare i negazionisti della PrEP, la ricerca ormai considera obsoleta la PrEP con Truvada e al CROI ci sarà un simposio intitolato Innovations in PrEP.

Dalla Preliminary Agenda/Schedule Of Events si vede che ad aprire il congresso c'è il solito Workshop for New Investigators, che consiglio a tutti di seguire, perché è molto più facile delle presentazioni delle singole ricerche e consente di capire a che punto è la ricerca su HIV in alcuni campi cruciali - dalla comprensione sempre più sottile di HIV ai soliti ostacoli posti alla cura dal reservoir latente, dagli studi sui vaccini alle complessità in prospettiva delle complicazioni dell'infezione trattata con la ART.

Molto interessante sarà senz'altro lunedì 22 la lecture inaugurale di Bruce Walker su T Cell Control of HIV: Implications for Vaccines and Cure.

Martedì si entra nel vivo del congresso con due sessioni plenarie, una dedicata agli anticorpi neutralizzanti - Harnessing Neutralizing Antibodies for Prevention and Treatment - ed una dedicata a stabilire lo stato dell'arte della ART - Antiretroviral Therapy: Where Are We Now? Where Are We Going?

La sessione orale di abstract dedicata a Viral Reservoirs/Antiretroviral Therapy Randomized Clinical Trials vedrà la presentazione dei risultati di tante sperimentazioni che stiamo seguendo e sarà da vedere tutta. Così come - anche se magari in seconda battuta - saranno da seguire le sessione su Complications from Head to Toe e su Global Burden and Morality of Cancer in HIV (forse mortality? la moralità del cancro è una follia che spero nessuno voglia discutere al CROI ...).

HIV Persistence and Latency Reversal - inutile che dica altro.

Nel pomeriggio di martedì, due simposi: Molecular Interplay from Virus to Host - che sarà probabilmente troppo tecnico perché ne parliamo qui; e A Beautiful Mind: Keeping It - come in tutti gli ultimi anni, l'infezione nel sistema nervoso centrale è argomento studiatissimo.

Mercoledì mattina una sessione plenaria su Progress in Gene Therapy for HIV Cure - anche su questo non serve che spenda troppe parole adesso.

Dalle tre sessioni di presentazione orale di abstract Reservoirs, Relapse, and Remission, Pushing Frontiers of Adaptive Immunity e Drugs: Front [from?] Discovery to Challenges in Clinical Use arriveranno probabilmente interessanti novità [rileggere quel che si scrive prima di pubblicarlo - o anche dopo, va bene lo stesso - deve far parte di quelle obsolescenze per le quali dobbiamo essere grati agli smart phone. Speriamo che gli organizzatori del CROI non siano altrettanto sciatti nella pubblicazione degli abstract.]

Ci saranno nel pomeriggio due sessioni su problemi di patogenesi da seguire: una sui problemi cardiovascolari - Stroke: Incidence and Risk Factors più il simposio su Pathogenesis and Consequences of Metabolic Complications - e una su quello che è argomento di moda quant'altri mai, il microbioma, che al CROI viene affrontato però secondo razionalità scientifica e non per vendere yoghurt magici - HIV and Microbiomes (a chi ha seguito le discussioni sul fecal trasfer qualche anno fa segnalo che - come prevedemmo allora - si è arrivati a studiarlo nelle persone con HIV. Cfr. la presentazione di Ma Somsouk, et al. intitolata Fecal Microbial Transplantation: Safety and Engraftment During Treated HIV Infection).

Sempre mercoledì pomeriggio, ci sarà un simposio dedicato ai linfonodi: Location, Location, Location: The Lymph Node - forse sarà questa l'occasione per veder discutere di ongoing replication nei santuari farmacologici?

Il congresso si chiude giovedì con un simposio sulle cellule NK da cui mi aspetto molto: Natural Born(e) Killers.

[mammadipi]

Sono pentitissima di non aver mai studiato l'inglese, quindi poi ti disturberò per qualche chiarimento. Ti ringrazio anticipatamente.

[Dora]

Sono pentitissima di non aver mai studiato l'inglese, quindi poi ti disturberò per qualche chiarimento. Ti ringrazio anticipatamente.

Certo cara, spero solo di riuscire a risponderti (comunque sia, ci proverò).

[Blast]

Io aspetterò che qualcuno parli dei macrofagi, questi sconosciuti

[Dora]

Finalmente è stato messo online il programma completo.
Nei prossimi giorni preparerò un post con degli appunti sulle cose che secondo me sono da seguire. Per ora, il programma può essere scaricato da qui:

• Program at a Glance

[Dora]

APPUNTI SUL PROGRAMMA DI CROI 2016 – gli imperdibili secondo Dora

Con la premessa che se il mio interesse prevalente, invece che la ricerca di una cura, fossero la patogenesi o le co-infezioni, o la prevenzione, questo post sarebbe certamente molto diverso, vi elenco alcune presentazioni (lezioni e abstract presentati oralmente) e alcuni titoli di poster che mi sembrano meritevoli di essere seguiti con attenzione. Uno o due asterischi indicano che la mia attenzione sarà particolarmente concentrata, non che ne scriverò necessariamente nell’HIVforum.

Ecco una prima lettura del PROGRAM AT A GLANCE:

Workshop for New Investigators and Trainees – lunedì

- Molecular Virology: Advances in the Understanding of HIV - Wesley I. Sundquist
- * Immunology and Vaccines - Richard A. Koup
- ** The HIV Latent Reservoir: Obstacles and Strategies to a Cure - Huldrych F. Günthard
- Unraveling the Complexities of Long-Term Complications of Treated HIV Infection - Judith S. Currier


Bernard Fields Lecture – lunedì

13 ** T Cell Control of HIV: Implications for Vaccines and Cure - Bruce D. Walker


Plenary Session – martedì

15 ** Harnessing Antibodies for HIV-1Prevention and Treatment - John R. Mascola
16 ** Antiretroviral Therapy: Where Are We Now? Where Are We Going? - Joseph J. Eron


SIV and HIV Pathogenesis – oral abstracts – martedì

22 CD8 T Cells Are Required to Suppress Viremia in SIV-Infected ART Treated Macaques - Emily K. Cartwright (Silvestri)


Viral Reservoirs/Antiretroviral Therapy Randomized Clinical Trials – oral abstracts – martedì

25 ** Safety, Immunologic and Virologic Activity of Anti-PD-L1 in HIV-1 Participants on ART - Joseph J. Eron
26LB ** Effect of Sequential Vacc-4x/GM-CSF Immunization and Romidepsin on the HIV Reservoir - Ole S. Søgaard
31LB ** Cabotegravir+Rilpivirine as Long-Acting Maintenance Therapy: LATTE-2 Week 32 Results - David A. Margolis
32LB ** ACTG 5340:The Effect of VRC01 on Viral Kinetics After Analytic Treatment Interruption - Katharine J. Bar


Complications from Head to Toe – oral abstracts – martedì

44LB Aspirin Fails to Impact Immune Activation or Endothelial Function in Treated HIV - Meagan K. O’Brien


HIV Persistence and Latency Reversal – themed discussion – martedì

377 Naïve CD4+ T Cells Harbor a Large Inducible Reservoir of Latent HIV-1 - Jennifer Zerbato
378 Follicular Tregs Reduce HIV Replication and Reactivation From Latency Ex Vivo - Brodie Miles
375 Dendritic Cell-T-Cell Culture Facilitates HIV Latency in Proliferating CD4+ T Cells - Nitasha A. Kumar
379 ** A Subset of Infectious Proviruses Persist and Expand Following Activation Ex Vivo - John K. Bui (Mellors)
380 Transcription of Novel HIV-1 RNA Species in the Setting of Undetectable Virus - Hiromi Imamichi


A Beautiful Mind: Keeping It – simposium – martedì

62 CNS as an HIV Reservoir - Ronald I. Swanstrom


Plenary session – mercoledì

78 ** Progress in Gene Therapy for HIV Cure - Paula M. Cannon


Reservoirs, Relapse, and Remission – oral abstracs – mercoledì

80 Investigating the Mechanisms that Control HIV Transcription and Latency In Vivo - Steven A. Yukl
81 Human Galectin-9 Is a Potent Mediator of HIV Transcription and Reactivation - Mohamed Abdel-Mohsen
82 PD-1+ and Tfh Cells Represent the Major Source of HIV-1 Replication-Competent Virus - Riddhima Banga1;
83 ** Rapid Accumulation of Defective Proviruses Complicates HIV-1 Reservoir Measurements - Katherine M. Bruner (Siliciano)
85 ** ART Reduces Cellular HIV RNA but Not the Fraction of Proviruses Transcribing RNA - Mary F. Kearney
86 ** Restricted HIV-1 Diversity and Clonal Expansion Following Cytoreductive Chemotherapy - Timothy J. Henrich
87 * Virological Remission After ART Interruption in African HIV-1 Seroconverters - Morgane Gossez


Pushing Frontiers of Adaptive Immunity – oral abstracts – mercoledì

88 An Infant bNAb With Low Somatic Hypermutation Contributes to Polyclonal Breadth - Cassandra Simonich
89LB * Virus, Host, and Disease Factors Govern HIV-1 Broadly Neutralizing Antibody Induction - Alexandra Trkola
90 ** Clinical Safety and Pharmacokinetics of IV and SC VRC01, a Broadly Neutralizing mAb - Kenneth H. Mayer
92 * Potency and Kinetics of Autologous HIV-1 Neutralizing Antibody Responses During ATI - Brenda Salantes
93LB ** PD-1 Blockade as an Adjunct Therapy to ART and Potential to Destabilize SIV Reservoir - Geetha Mylvaganam
95LB ** Repeated TLR7 Agonist Treatment of SIV+ Monkeys on ART Can Lead to Viral Remission - James B. Whitney


Drugs: From Discovery to Challenges in Clinical Use – oral abstracts – mercoledì

97 * HIV-1 Combinectin BMS-986197: A Long-Acting Inhibitor With Multiple Modes of Action - Mark Krystal
98 Long-Acting Oral and Parenteral Dosing of MK-8591 for HIV Treatment or Prophylaxis - Jay Grobler


HIV and Microbiomes – themed discussion – mercoledì

260 Distinct Gut Microbiota Composition in Gay Men - Muntsa Rocafort
261 Impact of HIV-Associated Changes in the Gut Microbiome on Disease Progression - Jesús Luévano
263 Enhancement of Microbiota in Macaques Leads to Beneficial Immune Function Modulation - Jennifer A. Manuzak
264 Fecal Microbial Transplantation: Safety and Engraftment During Treated HIV Infection - Ma Somsouk (McCune)


Location, Location, Location: The Lymph Node – symposium – mercoledì

128 Are Follicular Dendritic Cells a Reservoir for HIV? - Michael C. Carroll
129 * Imaging Lymphoid Tissues to Understand Viral Persistence and Impaired Function - Jacob D. Estes
130 The Lymph Node, Cytotoxic T cell, and HIV/SIV Infections - Elizabeth Connick


HIV Virology: Putting It All Together – oral abstracts – giovedì

136 SERINC3 and SERINC5 Are Novel Antiviral Proteins Antagonized by HIV-1 Nef - Yuanfei Wu
140 1970s HIV-1 Genomes Reveal the Early History of the North American HIV/AIDS Epidemic - Michael Worobey


Pathways to Eliciting Antibody Responses – themed discussion – giovedì

303 Broadly Reactive Neutralizing Activity Within the First 6 Months of HIV-1 Infection - Amanda Fabra García
317 Immunogenicity and Efficacy of ALVAC-HIV/gp120-Clade C in Alum Regimen in Macaques - Luca Schifanella


Natural Born(e) Killers – symposium – giovedì

178 NK Cell-Mediated Recognition of HIV - Marcus Altfeld
179 Signatures of Protective NK Cell Responses - Catherine A. Blish
180 Supercharging NK Cells for Cure - Jonathan Karn
181 Exposing Env: A New Strategy to Target HIV-1–Infected Cells by ADCC - Andrés Finzi



POSTER

HIV and Intestinal Integrity

234 Microbial Translocation and Inflammation Responses to Lubiprostone in HIV Infection
235 A20 May Contribute to Recovery of Intestinal Epithelial Function in Treated HIV
238 Probiotics Module Th1/Th17 and IFN Response in HIV Patients on Suppressive Cart
239 * Cenicriviroc Decreases sCD14 and LBP Levels Without Affecting Gut Permeability


HIV Effects on CD4+ T Cells

240 ** In Vivo Evidence for a Role of Pyroptosis in HIV Pathogenesis
241 Caspase Inhibition Prevents HIV Replication and Cell Death in Human Lymphoid Tissue
243 Dead Cells Tell No Tales: The Enigma of Discerning HIVInfected Cell Death


Immunopathogenesis

252 IL-7 Responsiveness Is Impaired in CD4 T Cells From HIV Immune Failure Patients
255 Antioxidants Improve Lung Immunity and T-Cell Proliferation in Immune Non-Responders
257 Immunomodulatory Effects of Recreational Marijuana Use in Youth Living With HIV-1
258LB * T Regulatory Cell Depletion in Controller Macaques Reactivates SIV and Boosts CTLs
259LB * Increased Effector CD8 Lymphocyte Trafficking to Lymph Nodes Induced by hetIL-15


Antibody Responses to HIV Infection: What Drives Them and How They Affect the Virus

303 Broadly Reactive Neutralizing Activity Within the First Six Months of HIV-1 Infection
304 New Family of Neutralizing Antibodies in HIV Asymptomatic Long-Term Nonprogressors
305 * Antibody-Mediated Killing of HIV Reservoirs by HIV Controllers
307 Humoral Immune Pressure Selects for HIV-1 CXCR4-Using Variants
311LB ** Effect of Infusion of Broadly Neutralizing Antibody VRC01 on HIV Plasma Rebound


Cellular Immunity: Change to Cytotoxic T Lymphocyte and NK Cells

312 CD8 T Cells From HIV Controllers Recognize and Kill HIV+ Non-Activated CD4 T Cells


Novel HIV Reservoirs

330 Persistence of HIV-Infected Alveolar Macrophages After Suppressive ART
331 Evidence of HIV Evolution in Lymphatic and Cancer Tissues in ART+ Patients
332 Role of Transitional-Memory T Cells in Productive HIV Reservoir in ULTRASTOP Patients
334 Germinal Centre T and B Cells in Lymph Node Fine-Needle Biopsies During HIV Infection
335 Tcm CD4 T-Cell Infection Associates With Immune Failure and HIV Persistence on ART


HIV Reservoir: Measurement and Mechanisms of Persistence

336 * Sustained HIV Release by Single Persisting CD4+ T Cells During Latency Disruption
337 ** Analysis of HIV Proviruses in Clonally Expanded Cells In Vivo
339 ** Optimization of PCR Amplicons to Predict Clonality of Full-Length HIV-1 Sequences
340 ** Clonal Expansion of Replication-Competent Proviruses Is Common in Individuals on ART
341 * A Novel Assay to Quantify Replication-Competent Latent HIV-1 From rCD4+T Cells
342 * Cellular HIV-1 RNA/DNA As Biomarkers of Inducible Virion Production


Tissue Reservoirs of HIV: Anatomic and Imaging Studies

343 FDG PET/CT Imaging of Lymph Nodes As a Measure of the HIV Reservoir in Humans


Exposure Response: Learning to Improve Safety and Efficacy

425 * HIV-1 Maturation Inhibitor BMS-955176: Pharmacokinetic and Exposure-Response Analysis
437LB ** A Single Monotherapy Dose of MK-8591, a Novel NRTI, Suppresses HIV for 10 Days


HIV and Microbiomes

264 Fecal Microbial Transplantation: Safety and Engraftment During Treated HIV Infection
265 Effects of HAART Treatment on the Microbiome of HIV+ Patients
266 Diet Effects on the Gut Microbiome of People Living With HIV-1


Evaluating HIV Vaccines: Preclinical to Clinical

322 * Poly-ICLC, a TLR Agonist, Is Safe and Tolerable in HIV-Infected Individuals


Impact of Antiretroviral Therapy on Viremic Control and Tissue Reservoirs

346 Relationship Among Viral Load Outcomes in HIV Treatment Interruption Trials
347 * Viral and Immune Characteristics of HIV Post-Treatment Controllers in ACTG Studies
348 HIV-1 in the Blood and Intestine Contributes to Viremia During Treatment Interruption
350 * Impact of Long-term Antiretroviral Therapy (ART) on Cellular HIV and Inflammation
352 Predictors of Viral Control After ART Interruption in SIV-Infected Rhesus Macaques
353 Antiretroviral Therapy in SIV Natural Hosts: Implications for AIDS Pathogenesis


Approaches to Reactivating HIV and Gene Therapy

354 ** Bryostatin-1 for Latent-Virus Reactivation: A Phase I, Double-Blind Clinical Trial
355 Clinical Administration of Vorinostat Increases NK Cell Capacity to Produce IFN-g
356 * CCR5 Gene-Edited Cells Undergo Positive Selection in SHIV-Infected Nonhuman Primates
357 * Predicting Determinants of Long-Term HIV Control With Gene Therapy Strategies
358LB ** T-Cell Homeostasis and CD8 Responses Predict Viral Control Post SB-728-T Treatment


HIV Integration

359 ** Integration Analysis of Latently Infected Cell Lines: Evidence of Ongoing Replication
360 * HIV Integration Sites in Cellular Models of Viral Persistence
361 Clonal Integration Site Frequency and Replication-Competent Virus in Patients on ART
363 Inhibition of the IN-LEDGF/p75 interplay by LEDGINs Reduces Reactivation From Latency


Central Nervous System: HIV Entry, Reservoirs, and Compartmentalization

400 CNS Compartmentalization of HIV-1 and Sensitivity to Neutralizing Antibodies
402 Persistent HIV-1 in the CNS During Therapy: Evidence of a Viral Reservoir in the CNS


Pharmacokinetics in Compartments

447 Multispecies ARV Distribution in Intestinal Tissue by Mass Spectrometry Imaging (MSI)


Antiretroviral Therapy: Randomized Clinical Trials

470 Doravirine 100mg QD vs Efavirenz +TDF/FTC in ARTNaive HIV+ Patients: Week 48 Results
471 Tolerability and Acceptability of Cabotegravir LA Injection: Results From ECLAIR Study
472 Attachment Inhibitor Prodrug BMS-663068 in ARVExperienced Subjects: Week 96 Analysis
474 Effect of Immediate ART on Risk of Severe Bacterial Infections: The START Trial
475 Increased Quality of Life With Immediate ART Initiation: Results From the START Trial


Immune Effects of Antiretroviral Therapy

298 ** ACE-Inhibitors to Decrease Lymphoid Fibrosis and the Size of the Latent Reservoir


Stem Cells

364 ** Treatment of HIV and AML by Allogeneic CCR5-d32 Blood Stem Cell Transplantation
365 HIV-1 Viral Rebound Following Allogeneic Hematopoietic Stem-Cell Transplantation
366 * A Tale of Two Stem-Cell Transplantations in HIV+ Patients: Clues to Eradicate HIV
367 * Ex Vivo Determination of Stem-Cell Transplantation Graft-Versus-HIV Reservoir Effects


HIV Persistence, Latency, and Reactivation

368 The HIV-1 Antisense Transcript AST Is an Inducer of Viral Latency
369 Differential Effect of Selenium on HIV Replication and Reactivation in Primary Cells
371 Reactivation of Latent HIV-1 in J-Lat T Cells by Type I Interferon Agonists
374 * Effect of Primary CD8 T Cells on Romidepsin and Bryostatin-Treated CD4 T Cells
377 Naïve CD4+ T Cells Harbor a Large Inducible Reservoir of Latent HIV-1
379 ** A Subset of Infectious Proviruses Persist and Expand Following Activation Ex Vivo


Preclinical Studies of Activity and Resistance

462 * A Quantitative Model of ART Efficacy Explains the Clinical Success of Dolutegravir
464 Maturation Inhibitor BMS-955176: Activity Against PI-Resistant Clinical Isolates
468 PBMC From Patients on Chronic Treatment With Dasatinib Are Resistant to HIV Infection
469LB * Efficacy of an Engineered Bispecific Anti-HIV Antibody in Humanized Mice

[Dora]

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