[CROI 2023] Seattle, Washington, 19-22 febbraio

Le principali novità dai congressi riguardanti la malattia da HIV (CROI, IAS/IAC, ICAAC...) e i nostri commenti.
Dora
Messaggi: 7493
Iscritto il: martedì 7 luglio 2009, 10:48

[CROI 2023] Seattle, Washington, 19-22 febbraio

Messaggio da Dora » martedì 7 febbraio 2023, 9:00

Immagine


Tra meno di due settimane, torna l'annuale appuntamento del CROI. Torna prevalentemente in presenza, a Seattle dal 19 al 22 febbraio, dopo essere stato virtuale negli anni peggiori della pandemia da Covid.

Quest'anno è il 30° e l'anniversario verrà ricordato nella sessione d'apertura nel pomeriggio di domenica 19 in due presentazioni:

- CROI AT 30: PROGRESS IN HIV THROUGH THE LENS OF CROI, con il ricordo di ricerche passate e la menzione delle sfide che ancora devono essere affrontate;

- CROI: A 30-YEAR CHRONICLE OF HIV/AIDS RESEARCH PROGRESS, in cui il CROI onora la carriera di Anthony Fauci, che è appena andato in pensione e avrà l'occasione di offrire la propria personale prospettiva sulla scienza dell'HIV/AIDS dagli esordi ad oggi.

Il programma completo sarà pubblicato la settimana prossima e allora ci sarà modo di vederne alcuni dettagli. Quella che segue è una panoramica molto parziale, basata sul programma preliminare e sui criteri che tradizionalmente mi hanno portata a scegliere di parlare di certe ricerche, tralasciandone altre altrettanto importanti (HIV e non altri virus o batteri, anche se quest'anno SARS-CoV-2 continua ovviamente ad avere una parte molto rilevante negli interessi del congresso, HBV ha soppiantato HCV, TB resiste e fa il suo ingresso MPOX; ricerca su nuovi farmaci e possibili cure invece che patogenesi e vecchi e nuovi disturbi; terapia invece che prevenzione; adulti invece che bambini).

Il congresso si apre con il solito WORKSHOP FOR NEW INVESTIGATORS AND TRAINEES, che dall'anno scorso è intitolato alla memoria di Scott Hammer. Seguire queste presentazioni è molto utile, perché sono relativamente semplici e permettono di avere un'idea generale dei temi del CROI. Ne segnalo in particolare due:

- ADVANCES IN HIV TREATMENT STRATEGIES, tenuta da Monica Gandhi, University of California San Francisco;
- ADVANCES IN HIV CURE, che torna ad essere tenuta da John Mellors, University of Pittsburgh.

La BERNARD FIELDS LECTURE quest'anno è tenuta da Alan S. Perelson, Los Alamos National Laboratory, e dedicata a MODELING THE DYNAMICS OF HIV INFECTION: ESTABLISHING PARADIGMS FOR TREATMENT AND CURE.

Martedì 21 ci sarà l'importante sessione plenaria curata da Janet Siliciano, Johns Hopkins University School of Medicine, e dedicata a HIV RESERVOIRS: OBSTACLES TO A CURE (un altro dei temi che ricorrono ogni anno al CROI), cui corrisponderà una sessione di abstract orali dallo stesso titolo, moderata da Katharine Bar, University of Pennsylvania, e Linos Vandekerckhove, HIV Cure Research Center, Ghent University.

Sempre martedì, è stata introdotta all'ultimo momento una sessione speciale dedicata alla recente débâcle del vaccino MOSAICO. Due le presentazioni:

- OVERVIEW OF THE MOSAICO HIV VACCINE TRIAL - Susan P. Buchbinder, San Francisco Department of Public Health;
- HIV VACCINE DEVELOPMENT POST-MOSAICO - Lawrence Corey, Fred Hutchinson Cancer Research Center.

Mercoledì, oltre a temi importanti di patogenesi (IMMUNOPATHOGENESIS AND VACCINES, NEUROPATHOGENESIS AND NEUROLOGIC COMPLICATIONS OF HIV AND SARS-COV-2, CARDIO-METABOLIC COMPLICATIONS OF HIV), una discussione su CELLULAR IMMUNE CONTROL OF HIV, moderata da Marcus Altfeld, Leibniz Institute for Virology, Hamburg e un affascinate simposio su THE VIRUSES THEY ARE A CHANGING: HOW THE IMMUNE SYSTEM RESPONDS.

Per la prima volta arriva al CROI il devastante problema della disinformazione e della comunicazione scientifica (era ora, eh?), con una discussione moderata da Jonathan Mermin, CDC, e Jon Cohen, Science - SCIENCE COMMUNICATION IN THE AGE OF MISINFORMATION:

- WHAT CAN I DO? THE CHALLENGE OF HEALTH MISINFORMATION ONLINE - Emily Vraga, University of Minnesota;
- COUNTERING VACCINE AND HEALTH MIS AND DISINFORMATION: AN EVIDENCE-BASED APPROACH - Scott Ratzan, City University of New York;
- WHAT’S FUELING THE SPREAD OF MISINFORMATION: LOOKING BEYOND FAKE FACTS - Heidi Larson, London School of Hygiene & Tropical Medicine, Brussels.

E speriamo che gli scienziati che si muovono in rete abbiano imparato qualcosa dai disastri che hanno combinato negli ultimi anni.


Appena sarà pubblicato il programma completo, riprenderò il thread.

Un'ultima nota: non ho capito se tornerà la bella consuetudine del CROI di rendere pubblici i webcast subito dopo la conclusione delle rispettive sessioni, oppure se i materiali del congresso saranno disponibili solo per gli iscritti. Nel primo caso, cercherò di seguire le presentazioni orali e di aggiornare i thread esistenti delle ricerche o crearne di nuovi. Nel secondo, mi comporterò mestamente come negli ultimi anni.



Dora
Messaggi: 7493
Iscritto il: martedì 7 luglio 2009, 10:48

Re: [CROI 2023] Seattle, Washington, 19-22 febbraio

Messaggio da Dora » sabato 11 febbraio 2023, 7:14

Ecco il programma completo:

Immagine

Da segnalare - sessioni orali e relativi poster:

Martedì 21 - Oral Abstract Session-05 HIV RESERVOIRS AND CURE STRATEGIES (tutto, ma in particolare:)
  • - 136 THE IMPACT OF 3BNC117, 10-1074, AND LEFITOLIMOD ON HIV-1 PERSISTENCE: THE TITAN TRIAL - Ole S. Søgaar
    - 137 VIRAL AND HOST MEDIATORS OF PERSISTENT LOW-LEVEL VIREMIA - Abbas Mohammadi
    - 138 PROVIRUSES IN SELF-REACTIVE CD4+ T CELLS ARE A COMMON SOURCE OF RESIDUAL HIV VIREMIA - Fengting Wu
Themed Discussion-06 DYNAMICS OF PROVIRAL INTEGRATION
  • - 451 CTL SELECTION ENRICHES FOR HIV INTEGRATION SITE FEATURES AND EXPANDED CLONES IN VIVO - Noemi L. Linden
    - 452 IMPACT OF HIV RESERVOIR IN THE LOSS OF NATURAL ELITE CONTROL OF HIV-1 INFECTION - Carmen Gasca-Capote
    - 453 DISTINCT INTEGRATION SITES OF INTACT HIV-1 PROVIRUSES IN POST-TREATMENT CONTROLLERS - Isabelle C. Roseto
    - 455 EFFECT OF HIV-1 INFECTION AND VIRUS PRODUCTION ON CD4+ T CELL PROLIFERATION - Joshua T. Kufera
    - 456 A NOT-SO-STABLE RESERVOIR: HIV DRIVES INFECTED CELLS TO DIE AND DIVIDE - Sam Weissman
Themed Discussion-07 A VIRUS ON MY MIND: UNRAVELING LINKS BETWEEN HIV AND MENTAL HEALTH SYMPTOMS

Themed Discussion-08 LAI CAB/RPV: WHERE ARE WE NOW AND WHERE ARE WE GOING?


Mercoledì 22 - Oral Abstract Session-10 IMMUNOPATHOGENESIS AND VACCINES

Oral Abstract Session-11 NEUROPATHOGENESIS AND NEUROLOGIC COMPLICATIONS OF HIV AND SARS-CoV-2

Themed Discussion-10 CELLULAR IMMUNE CONTROL OF HIV dove le cellule NK ricevono una trattazione approfondita come mai prima

Themed Discussion-11 WEIGHT GAIN: DOES WHAT GOES UP ALWAYS COME DOWN?

Diverse sessioni di poster dedicate a elite e post treatment controllers

Poster Session-E2 DYNAMICS OF THE HIV RESERVOIR e Poster Session-E7 MECHANISMS OF HIV LATENCY

Poster Session-B3 HIV NON IMMUNO PATHOGNESIS, COINFECTION e Poster Session-B5 HIV IMMUNOPATHOGENESIS

Poster Session-E4 HIV RESERVOIRS IN CELLS AND TISSUES e Poster Session-E6 INTERVENTIONS TO TARGET THE VIRAL RESERVOIR
AND DELAY VIRAL REBOUND

  • - 428 REDUCTION IN HIV RESERVOIR MARKERS WITH GAG/POL/IL-12 DNA THERAPEUTIC VACCINATION
    - 429 DOUBLING DOLUTEGRAVIR DOSAGE REDUCES HIV PERSISTENCE MARKERS IN ART-TREATED ADULTS
    - 430 RANDOMIZED CONTROLLED TRIAL OF VRCO1 MONOCLONAL ANTIBODY DURING ACUTE HIV INFECTION
    - 431 BEAT2 PRIMARY TRIAL OUTCOMES: PEG-IFN-α2B +3BNC117 & 10-1074 IN CHRONIC HIV INFECTION
    - 432 LONG-TERM PROTECTION OF CD4+ T CELLS AGAINST HIV BY ONE-YEAR TREATMENT WITH PONATINIB
    - 433 A PLACEBO-CONTROLLED RANDOMIZED TRIAL OF THE HTI IMMUNOGEN VACCINE AND VESATOLIMOD
    - 434 HIV-1 VIRAL RESERVOIR REACTIVATION AFTER CCR5 DELTA 32/32 STEM CELL TRANSPLANTATION
    - 435 REBOUND DYNAMICS FOLLOWING IMMUNOTHERAPY WITH AN HIV VACCINE, TLR9 AGONIST, AND bNAb
    - 436 HIV GAG X CD3 SOLUBLE TCR BISPECIFIC: SAFETY AND ACTIVITY IN A FIRST IN HUMAN TRIAL
    - 437 VESATOLIMOD PHARMACODYNAMIC RESPONSE IS ASSOCIATED WITH TIME TO HIV REBOUND
Poster Session-E8 DYNAMICS OF PROVIRAL INTEGRATION SITES

Poster Session-F5 CNS HIV INFECTION, PERSISTENCE, AND CURE STUDIES

Poster Session-H1 LAI CAB/RPV: WHERE ARE WE NOW AND WHERE ARE WE GOING?

Poster Session-I1 HIV RESISTANCE EMERGENCE AND OUTCOMES

Poster Session-E3 IMMUNE PRESSURE ON THE HIV RESERVOIR e Poster Session-E5 INNOVATIVE APPROACHES TO TARGET THE
RESERVOIR


Poster Session-H2 ANTIRETROVIRAL THERAPY: PROSPECTIVE CLINICAL TRIALS

La lettura che ho fatto delle 170 pagine del programma è molto affrettata e ci sarà tempo per tornarci su. Ma già da questa prima scorsa si vede che è confermata, e anzi rafforzata, la tendenza di questi ultimi anni: per quanto attiene alla ricerca di una cura, i fallimenti di tutti i trial clinici hanno imposto un ritorno alla ricerca di base. Da questo CROI ci sarà tantissimo da imparare. Ma io avrò pochissimo da scrivere.



aktom
Messaggi: 57
Iscritto il: lunedì 6 aprile 2015, 14:02

Re: [CROI 2023] Seattle, Washington, 19-22 febbraio

Messaggio da aktom » sabato 11 febbraio 2023, 10:14

Non vedo però nessun riferimento al primo paziente trattato con editing genetico da kamel Khalili , penso che sarebbe interessante sapere le prime reazioni al trattamento …



Dora
Messaggi: 7493
Iscritto il: martedì 7 luglio 2009, 10:48

Re: [CROI 2023] Seattle, Washington, 19-22 febbraio

Messaggio da Dora » sabato 11 febbraio 2023, 10:59

aktom ha scritto:
sabato 11 febbraio 2023, 10:14
Non vedo però nessun riferimento al primo paziente trattato con editing genetico da kamel Khalili , penso che sarebbe interessante sapere le prime reazioni al trattamento …
Khalili non presenta lavori al CROI. Quando parteciperà a qualche congresso importante o pubblicherà qualcosa sulla sperimentazione, ne scriverò.




Dora
Messaggi: 7493
Iscritto il: martedì 7 luglio 2009, 10:48

Re: [CROI 2023] Seattle, Washington, 19-22 febbraio

Messaggio da Dora » lunedì 20 febbraio 2023, 6:33

Il 30° CROI è ufficialmente iniziato.






Dora
Messaggi: 7493
Iscritto il: martedì 7 luglio 2009, 10:48

Re: [CROI 2023] Seattle, Washington, 19-22 febbraio

Messaggio da Dora » martedì 21 febbraio 2023, 6:39

Su IDSE Marie Rosenthal, MS, scrive una sintesi dell'intervento di Fauci, che ricorda i 30 anni di storia del CROI:
Dr. Fauci to Young Scientists: Take the Ball and Run With It

Much of the clinical and basic science research presented through the years at CROI becomes the standard of care, according to Anthony Fauci, MD, the former director of the National Institute of Allergy and Infectious Diseases (NIAID).

Thirty years ago, Dr. Fauci was instrumental in starting CROI, and as the keynote speaker for CROI 2023, he gave some insights into what that meeting has meant to HIV science, medicine and patients.

“The point I want to make specifically to the young people in the crowd—the pre-docs, the postdocs, the young investigators—is that what happens in this meeting in a very incipient form over a period of time becomes the reality of what we are dealing with and then the implementation of something that’s clinically actionable,” he said.

The CROI Origin Story

Two events precipitated the development of the CROI meeting, he explained. American scientists, who worked for government institutions like NIAID, were going to the International AIDS Conference being held in Florence, Italy, in the early 90s, but their trips were derailed—many being called back while in Florence—because government officials thought it was a waste of resources, explained Robert T. “Chip” Schooley, MD, of the University of California San Diego.

“It was really a very unusual situation,” Dr. Fauci explained. No one was a villain in the move, he said, but it demonstrated a lack of understanding about the importance of sharing science and knowledge about this new deadly disease.

The second event caused much international consternation, when people with HIV were banned from entering the United States.

“So, we had two conflating really bad things happening associated with that meeting in Italy. There were literally investigators who got on a plane, got to Florence, turned around and came back. These were investigators, and at the NIH as well as some of our Intramural Research program people, the people that you deal with in your trails, in your contracts. So there were two things. One, getting too many people there was not a good thing, according to them. And two, there were these travel restrictions,” Dr. Fauci explained.

In protest the International AIDS meeting, which was supposed to be held in Boston that year, was moved to Amsterdam.

“To make matters worse, HHS [Department of Health and Human Services] then cut the roster for the Amsterdam meeting. So at that point we said, ‘Enough is enough. We’re going to have to do something different,’” he said.
Although they respected the international meetings, Dr. Fauci and his colleagues realized they needed a place for American students, fellows and postdocs to share information about HIV.

The first meeting was sponsored by the NIAID, National Foundation for Infectious Diseases and American Society for Microbiology. Eventually, the government stepped away from the meeting. Today the meeting is affiliated with the International Antiviral Society–USA.

Dr. Fauci took a quick trip down memory lane to demonstrate the cutting-edge science that was introduced at CROI through the years, hoping to influence young investigators “because you are a part of a tradition; we are looking at you to carry on after people like me are no longer around,” he said.

The year 1995 showed some promising work on the pathogenesis and viral dynamics, function of nef, human herpesvirus 8 was the cause of Kaposi sarcoma, and combination therapy with lamivudine (3TC) plus zidovudine (AZT) was more effective than monotherapy. By 1996, people were prescribing a three-drug regimen, he said, and many people were looking at viral loads.

“Things really started to take off because we had the insights on pathogenesis and viral dynamics,” he said. “We had a really giant step that wasn’t the endgame, yet. And that was when we had a combination of two drugs, AZT and 3TC, which was really an important drug because we were playing around with other two-drug combinations, DDI [didanosine] and DDC [zalcitabine] that really didn’t do very well.”

These types of discoveries wound up blending basic science with clinical medicine, which has always been a staple of CROI, according to Drs. Fauci and Schooley.

“We went from the evolution of a single drug with a little dip in the viremia that was certainly non-sustainable. And then with the two drugs, a great diminution, again, not sustainable. And then the thing that blew everybody out the water, as you’ve heard from other individuals with a triple combination, you had a profound minutia undetectable and it was sustainable,” Dr. Fauci explained.

Patients went from taking 28 pills per day to one or two, or even a long-acting injectable, all of which reduce viral loads to undetectable levels and allow people with HIV to live near-normal lives.

“When I was taking care of patients prior to ART [antiretroviral therapy] back in the early 80s, there are many in the audience who had an experience that was a very dark, painful experience that I had back then that almost every one of our patients died. Now with the medications that we now have, individuals could lead essentially a normal life span,” Dr. Fauci said. “There was several years that we were putting Band-Aids on hemorrhages.”
Another important finding was delivered in 1999 in Chicago about the origins of HIV-1 (abstract S2). Through biogenetic analysis, Beatrice Hahn and her colleagues found that HIV-1 occurred after SIV (simian immunodeficiency virus) jumped species from chimpanzee to humans—this was 18 years after the recognition of HIV.

“So the people who say, ‘Well, we’ve had COVID for three years and you still haven’t nailed down what the origin is, so we’ll never know. Hello, history? It took 18 years to do it with HIV,” he said, and the audience laughed.
Other breakthroughs included treatment as prevention (undetectable equals untransmissible, U=U), he said. “We heard from Yvette [Rachel, who spoke before Dr. Fauci]. U=U without a doubt, no argument.

But equally important is treatment for prevention or pre-exposure prophylaxis (PrEP), he said. Both ideas were presented at CROI before they became cornerstones of the ending HIV campaign in the United States.

A study presented by T.C. Quinn and R.H. Gray in 2000 (abstract 193) demonstrated zero transmission in 51 discordant couples with a viral load less than 1,500/mL. “We didn’t fully realize the implications of what that was going to be. So what happened is that over the next few years, the data on treatment as prevention became overwhelmingly compelling,” he said.

By the time the study was published in The New England Journal of Medicine, they had data from 415 heterosexual HIV-discordant couples in Rakai, Uganda, that found no transmission.

“Another study in 2014 showed the transmission risk for condomless sex and individuals with suppressive ART became more clear with the JAMA paper of the partner study after 58,000 condomless sexual acts, no link to HIV transmission.

“I have to admit, when I saw that data, I couldn’t believe it—zero transmission. And that’s why when people talk about U=U, it really is a scientific fact,” Dr. Fauci said.

Other important abstracts demonstrated the efficacy of PrEP, long-acting cabotegravir and the capsid inhibitor, lenacapavir (Sunlenca, Gilead), both of which were later approved by the FDA.

Ms. Raphael, the co-founder of Advocacy for Prevention of HIV and AIDS in South Africa, who gave the Delany presentation, urged Dr. Fauci to continue the search for a cure and vaccine. “Before you leave, you must tell scientists to find a cure for HIV, to follow the legacy. You did it for COVID; I’m sure you can do it for HIV,” Ms. Raphael said.

“Yvette, you told me I had to talk about cure and vaccine,” he said, calling it unfinished business. “The unfinished business, it’s obvious—it’s cure and the vaccine and ending the HIV/AIDS epidemic,” Dr. Fauci said. “Remember, we made a plan in 2020 [announced at CROI 2019] that we wanted to end HIV by 2030, in 10 years. We can’t give up on that.

“I believe if we do everything right, what we’re talking about, even without an absolute cure and a vaccine [we can end HIV],” he said. “But that doesn’t mean you should not attempt to do that.

“I mean I’m a realist, but I’m also a cautious optimist. And I really believe that we can end the HIV/AIDS epidemic in this country and globally,” he said, admitting that he wanted this to happen on his watch.

“I would’ve liked to have been here active as the director of NIAID when that happened, but it’s not going to happen because I’m no longer the director of NIAID.

“It’s going to happen with the people who are pre-docs, postdocs and early young investigators. It’s not going to happen unless you do it. So please take the ball and run with it,” Dr. Fauci urged.

Molto interessante anche l'intervento di Yvette Raphael, co-fondatrice di Advocacy for Prevention of HIV and AIDS in Sud Africa, che ha tenuto la "MARTIN DELANEY PRESENTATION". Qui nella sintesi, sempre di Marie Rosenthal, su IDSE:

Yvette Raphael: Time to Address ‘Unfinished Work’ and Meet Women’s Needs



Dora
Messaggi: 7493
Iscritto il: martedì 7 luglio 2009, 10:48

Re: [CROI 2023] Seattle, Washington, 19-22 febbraio

Messaggio da Dora » giovedì 23 marzo 2023, 6:55

A un mese dal congresso, i
sono online.



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