If so, if a treated patient spreads the virus, will that new patient carry an innoculated virus? Or will they suffer a standard infection?
This will enable it to be supplied at a non-exploitative price to Africa and Asia.
Do we know, how many of those deaths are due to limitations of existing treatments, versus how many are due to health care access issues?
I'd love to see more work done towards other incurable viruses like HSV (no vaccine) and HPV (limited vaccine)
It's millions of times easier to copy than to discover. Discovery needs paying for, and the places that don't discover aren't owed things by places that do.
However, if they can tweak the drug and make it something that escapes the patent and still works then good for them and everyone else. Though mindful large pharma is rather tight and lawyer-heavy when it comes to protecting their IP.
As of now it is under patent that expires in 2032, and also not FDA approved, so with how long that process takes, either way, wont see it available anytime soon in drug regulated countries. But grey imports/black market trade in pharma drugs is not to be overlooked.
>AI Engineer @Varnan Labs
Bingo. A glance at their comment history shows this is a pattern for them
My sister, who is two years younger, was in 8th or 9th grade when this album came out. She's also a Weezer and Radio Head fan. Only a few years difference but I feel this genre came after me.
The devil may be in the details. E.g. if a COVID test shows negative, it doesn't mean that you can't spread it. This is partly because different tests have different sensitivities.
> I'm pretty sure
FYI, without citations, it is hard to distinguish credible experts vs people on the internet saying "trust me bro".
The HBV virus is also carcinogenic, which makes it unique[0] among the three big hepatitis viruses. Liver cancer is extremely aggressive and fast-killing, often reaching terminal stages before it is even detectable at all. It is one of the top three causes of cancer deaths worldwide.
Aside from the sheer number of people affected by this, it is also a horrible thing to experience. I have watched someone die from liver cancer, and I would not wish it on anyone.
Contrast to HSV, which is widespread (approximately half the population has at least one HSV latent infection) and causes very few problems beyond occasional irritation in virtually all cases that do not involve other comorbidities or immunocompromised status. HSV is also suppressible through antiviral treatment, making it generally untransmittable (if treated and suppressed) and unlikely to cause symptoms. Most people with HSV do not even bother to do this, which is if anything a testament to how little HSV affects their lives (most don't even know they have it, and there is no clinical justification for routine testing in otherwise healthy patients).
Of all infections pathogens for which I could wish a cure into existence, HSV would be extremely low on my list.
[0] While HCV can cause cancer if left untreated for a long time and if it causes cirrhosis, approximately one third of people clear HCV infection in the acute stages without any lasting ill effect. Of the remainder, it takes a long time for cirrhosis to develop, leaving plenty of time for treatment. First-line treatments are approximately 95-99% effective. So there is no clinical reason HCV needs to increase a person's risk for cancer, as long as they have access to medical care. The same is not true for HBV.
https://en.wikipedia.org/wiki/Hepatitis_B
Yes, there is an effective vaccine but not everyone has access to it for tons of reasons.
Probably you're thinking of trademark. A name cannot have a copyright
https://i-base.info/u-equals-u/
U=U probably does not apply to all diseases for the reasons you mentioned though.
Link between HSV and dementia
The vaccines are not a prohibited drug and so in most places if you have full blown prescribing rights (e.g. a Doctor or most "Advanced Practitioner" roles) the prescriber can "go off-piste" and just prescribe anything they believe is appropriate. So it's wrong to say it wasn't "allowed".
What you're thinking off are vaccine recommendations which are shots you'll get badgered to do if you don't ask and those didn't include people assigned male at birth in many countries at first because the studies were about Cervical Cancer and obviously most people assigned male at birth do not have a cervix because that's quintessentially female anatomy [Mother Nature doesn't give a fuck, with billions of humans all kinds of weird edge cases arise]. Later studies checked that, as you might now expect, preventing HPV infection also avoids warts and other cancers induced by this virus, and thus impacts humans who don't have a cervix.
The first Hep B vaccine in the US is given to all infants within 24 hours of birth (unless the child is already positive for Hep B or severely underweight). And then the second vaccine a month or so later and the third between ages 6 and 18 months old. Hep B vaccination is one of the most common vaccinations received in the US.
And also as a fun little fact the first Hep B vaccine was given exclusively to gay men for a decent while until it was deemed safe enough for the general population. It was also manufactured from the blood of gay men and needle based drug users.
The Hep B vaccine that came later was recombinant and that one was given to everyone from day 1 and that's the vaccine that's been more or less the main Hep B vaccine in use up to today. Recently there's at least one new one that has been approved but the original recombinant Hep B vaccine is still regularly given.
Also, about 3.5% of the world's population already has it. That's about 300 million people for whom a vaccine is pointless, and who are at dramatically higher risk of liver cancer (somewhere between 15-50% lifetime risk of an extremely deadly type of cancer), and for whom a cure would literally be life-changing, if available.
I think this is a bit of an unfair conclusion.
First, while you're correct that most people who have HSV have few symptoms (if any), you're discounting the fact that, because so many people are infected, there are millions upon millions who have highly-visible and highly-painful infections. Many of these people struggle with relationships and mental health as a result.
Second, HSV is associated with higher risk of HIV infection for obvious reasons.
Finally, discovering effective treatments for such a difficult virus would probably produce insights that have implications for other difficult-to-target viruses.
So I don't think we should dismiss HSV on the basis that it's so common and doesn't cause life-threatening symptoms. Medicine should pay adequate attention to infections that affect quality of life for large numbers of people.
Billions are spent on treatments for super rare diseases, many of which are terminal, and in the best cases the end result is often that pharmaceutical companies have drugs costing tens or hundreds of thousands of dollars that extend life by months (often with dubious quality of life).
Note that even on commercial sites they point this out:
https://www.medchemexpress.com/im-250.html
"Adibelivir (IM-250) is an orally active helicase-primase inhibitor. Adibelivir is effective against HSV infection and reduces reactivation of latent HSV."
See the word "reduces". Nowhere does it insinuate "permanently"; besides, permanently is simply a misnomer here. Even "latent" is a misnomer; it simply is integrated DNA. The only way to get rid of it is to cut this DNA out. Which therapeutic does so with efficiency? Even CRISPR-Cas9 has off-target effects. There are no permanent cures, and insinuating otherwise by using "permanently", is simply and factually incorrect.
And of course Covid tests are primarily mucous membrane based which is going to be inherently harder to evenly test compared to a blood sample where viral load is pretty evenly distributed.
At least for blood based diseases, detecting viral load via PCR testing is to such a sensitivity that if there's essentially any active viruses out and about or any active viral RNA floating around in cells then the tests come back positive.
And with sustained antiviral use testing is less about "do I have it/will I become contagious in the near future" (like coronavirus) and rather "is my antiviral regimen still killing the virus faster than it can wake up from latent genetic material sleeping in DNA".
The former is a timing problem from one shot testing the latter is monitoring a steady state to track that the treatment remains effective and when it ceases being effective there's a lag time between viral load being detectable and sufficient viral load to be meaningfully contagious.
By contrast, testing with rapid tests is mostly about seeing why you're sick before you go somewhere, and those tests probably don't need to be as sensitive. The hospital has capacity to treat people because of the PCR tests and so we can manage if some of the PCR tests are false-negative. Most people are vaccinated so we can tolerate some Covid-positive people mingling in public places now.
Tests aren't magical, and there are different tests with different capabilities. I'd suggest you learn about sensitivity versus specificity and learn how to compute the false positive, false negative, true positive, and true negative rates. It might be eye opening for you.
This is incorrect. The HBV vaccine is one of the most effective vaccines available for any pathogen, providing full immunity to over 95% of healthy infants, children, and young adults, and with that immunity typical lasting for at least 30 years (and likely for life).
If someone is one of the rare exception, tthat's easy to detect with blood titers, and the response is either to give them additional doses or to deliver an adjuvanted version (which is the same thing regularly done for other vaccines which are either less effective or primarily targeted at the elderly, who have weaker immune responses).
For the same reason we should be hoping for a treatment that can rid the body of VZV (chickenpox/shingles) because it is absolutely clear that the shingles vaccine has some protective effect against dementia.
A successful HSV vaccine would also almost certainly lead to a vaccine for epstein-barr, cytomegalovirus, and roseolovirus.
Even ignoring the thousands of connections HSV is suspected to have to other diseases, getting insight towards the other 3 big "uncured" HHVs would be a massive deal.
EBV/mono is a silent but debilitating disease that infects a near majority of the population even in "developed countries" and is all but confirmed as a requirement for developing multiple sclerosis. EBV is also directly connected to a long list of cancers as well.
cytomegalovirus and roseolovirus while less common in the developed world are still far too common and globally are major sources of harm for infants and young children.
Any steps towards effective vaccination against the broader family of HHVs would be monumental.
And we do know that it’s possible to reduce the pool of reactivation-competent HSV genomes by the presence of IFNα during primary infection:
https://pmc.ncbi.nlm.nih.gov/articles/PMC12764766/
This causes PML-NB formation → more viral genomes with H3K9me3 + ATRX → resists eviction by the H3K9me3S10ph “methyl/phospho switch” → stops Phase I HSV transcription (and VP16 expression).
Who’s to say an HPI like IM-250 isn’t altering epigenetic markers in viral episomes in this way? Innovative Molecules’ own press release states that some sort of permanent or semi-permanent modification may take place:
https://www.pharmaceutical-technology.com/analyst-comment/es...
>Furthermore, testing in animal models showed that adibelivir affected the latent viral reservoir, suggesting that it has potential as a long-term curative therapy for HSV.
A 6-month regimen of an experimental drug for the hepatitis B virus (HBV) added to standard antivirals has “functionally cured” 19% of people in two efficacy trials, meaning they can naturally control that virus without any further treatments. The results, published today in The New England Journal of Medicine (NEJM) and presented at Europe’s largest meeting on liver health, come from people whose chronic HBV infections were already relatively well controlled with the existing drugs, so its effectiveness in other populations that are more challenging to treat remains unknown.
The findings are “remarkable” and “a major step” forward for the field, hepatologist Anna Lok of the University of Michigan Medical School wrote in an editorial accompanying the NEJM editorial—although she cautioned it was far from a solution to a major global problem.
GSK in January had announced that its drug, called bepirovirsen (bepi), had positive results in two phase 3 efficacy trials that involved more than 1800 participants in 29 countries, but the company did not report any details. Many researchers anticipated that about 10% of trial participants would achieve natural suppression of HBV—what the field calls a functional cure—as that’s what was found in the earlier phase 2 bepi trials. The even more impressive result is “exciting news,” says Nick Walsh, an epidemiologist at Monash University who specializes in hepatitis diseases and was unconnected to the study. “This will certainly bring much needed attention to HBV and should accelerate further efforts to find a cure, which indeed needs to be urgently rolled out,” he says.
But Walsh and other HBV researchers stress that bepi’s unprecedented powers may well have a limited impact for most of the 240 million people worldwide living with chronic HBV infections, which kill 1.1 million each year. The World Health Organization estimates only 27% of infected people have been diagnosed, and of those, fewer than 5% receive treatment.
Chronic HBV infections can destroy the liver and ultimately kill if left unchecked. They currently require lifelong treatment, and less than 1% of patients who receive existing drugs can control the virus after stopping treatments. The most commonly used HBV drugs disrupt the ability of the virus to make copies of its genes by introducing into infected cells defective analogs of the nucleosides or nucleotides—nukes—that make up its DNA. Bepi, in contrast, is an antisense oligonucleotide that derails viral replication by binding to HBV’s messenger RNA, preventing it from making needed proteins and triggering its destruction. The drug separately stimulates immune responses against the virus.
The new phase 3 studies focused on the subset of the treated population for whom the standard drugs were working. Participants had relatively low levels of the viral surface protein, or antigen, in their blood and did not have HIV infections or liver scarring known as cirrhosis.
Two-thirds of participants added bepi shots for 24 weeks to their daily nuke pills, while a control group added placebo shots. Everyone then continued with nukes for another 24 weeks. Six months after stopping all treatment, 233 of 1220 people who had received bepi had functional cures—both undetectable HBV DNA and surface antigen—versus zero of 614 participants in the placebo arm. The functional cure rate went up to 26% in participants who entered the study with the lowest levels of the viral surface antigen. Side effects were common, but rarely severe.
When HBV infects adults, typically through sex or sharing needles during drug use, the immune system clears the virus about 90% of the time. In infants who become infected, mainly by mother-to-child transmission, their less mature immune systems falter more often—90% develop chronic infections. An infection becomes chronic when HBV integrates its DNA into human chromosomes and also forms an intractable miniature chromosome inside cells called cccDNA.
Like the nukes, bepi doesn’t eliminate the embedded cccDNA—a “sterilizing” cure—but it helps suppress HBV levels to low enough levels for a long enough period to reinvigorate immune responses against the virus. Many researchers see the functional cure bepi provides as a more realistic goal than a sterilizing cure. The new results are “a long-awaited milestone in the journey toward curing HBV infection,” says Fabien Zoulim, a hepatologist at Claude Bernard University Lyon 1.
Whether a bepi-induced functional cure is lifelong remains a key issue. Zoulim notes that the durability of surface antigen loss “requires further assessment through extended follow-up.” Data from the much smaller phase 2 studies of the drug have shown viral suppression for up to 3 years in more than 90% of the functionally cured patients, according to Melanie Paff, a GSK scientist who spoke at a press briefing last week.
GSK has already submitted the new phase 3 data to drug regulatory agencies in Europe, the United States, Canada, Japan, and China. The company expects at least some approvals to occur later this year. It has yet to announce how much the drug will sell for in wealthy countries and resource-limited ones. “We are committed to pricing which balances the value of innovation and patient access, and we’ll continue to work constructively with payers around the world to achieve this,” a GSK spokesperson told Science.
Despite the promise of bepi, some hepatitis B researchers remain frustrated that pharmaceutical companies have not made more of an effort to design even better, truly curative drugs. “There have not been enough collaborations within industry—each company tries to work on its own,” Lok says, “and we expect that a cure, for many patients, will require a multiprong approach.”