Not my area of expertise but even if we can address 99% of strains, wouldn't that last 1% just take over and become the new 100% leaving us back where we started? Or is the promise here that we can combine this discovery with another that solves that remaining 1%? Or, do the mutations of that last 1% make HIV less virulent or harder to transmit?
That unaffected 1% will still be limited by the rate of transmission which has been falling globally for decades because of growing access to birth control and antivirals, anonymous needle exchanges, and education. HIV isn't like a bacteria that grows out of control because the probability of transmission is highly dependent on the viral load, which varies significantly over the different strains and patients' lifetimes as their immune systems battle the virus. Even if eliminating 99% of strains only cures 50% of patients, those cured would have to have sexual or blood contact with the remaining 50% in order to get reinfected with the resistant strains.
HIV is a very expensive disease to treat and since it's no longer a death sentence, a significant amount of resources go towards a lifetime supply of drug cocktails for long term HIV patients (which is all of them). Even a 10% reduction in the number of infections would free up a massive amount of resources at the NHS, CDC, and other agencies best suited to put them to use dealing with the remaining infections. Like with cancer and drug resistance, there is no single panacea but that doesn't mean we can't make big leaps that help a lot of people. Fighting a virus like HIV takes a lot of victories, big and small, that chip away at the problem until, like with smallpox or polio, there are so few cases left that each can be dealt with individually by the public health infrastructure.
> a significant amount of resources go towards a lifetime supply of drug cocktails for long term HIV patients (which is all of them)
With my tin foil hat on, I've always wondered that now there is a very profitable business (for the big Pharma companies) out of just providing HIV positive people with drugs for years, that there is little appetite (again, inside big pharma) to actually 'cure' the disease...?
If one company has expensive treatments for a disease, and another company has a cure for it (at any price), which company is going to make more money? The one who has the cure, I'd say.
Multiple companies could collude to keep a cure off the market. But such cooperation would require all the collaborators to be simultaneously honorable enough to keep the agreement, and dishonorable enough to keep life-saving drugs away from people who are dying. I find that unlikely.
Meanwhile it would only take one traitor to make the deal collapse. Such a traitor could be any person who is in on the secret and also has a family member affected by the disease in question. It takes dozens of scientists, project managers, lab assistants, and random extra staff to create a new drug. I don't believe that many people can keep any kind of secret for any amount of time, let alone a secret as hot as a cure for (in this case) HIV.
This is why I don't believe in the idea that drug companies intentionally keep cures off the market. If no cure is available, it's probably because it genuinely doesn't exist yet.
> If one company has expensive treatments for a disease, and another company has a cure for it (at any price), which company is going to make more money? The one who has the cure, I'd say.
That's not quite correct. The company with the cure will make more money going forward. But not necessarily overall, and the difference there is important.
Let's say you're a venture investor in biotech, and you're thinking about whether to fund the development of an HIV cure or a better HIV treatment. Both will completely replace the existing market in HIV drugs. When you do the net present value calculation for the treatment however, you'll see that you have some probability of people staying on it basically forever. That means that over time, you can extract more money from it, which means of course that you ought to be willing to invest more money in developing it.
It is through this completely rational, non-evil mechanism that treatments may receive more funding than cures. Nobody here is suppressing anything, it's just that one of them will receive more funding than the other because it has a greater potential ROI.
They definitely don't have equal value. The potential revenue stream for the treatment is much higher than the cure. You have to subtract the probability that someone else finds a cure from that revenue stream, amortized and discounted over its lifetime.
So, it may be that sometimes that causes it to make sense to search for a cure (if there is a particularly promising pathway that someone else is likely to explore, for instance), but all else being equal, it probably makes more sense to fund treatments.
The initial cost of developing any new drug is extremely high. We're talking hundreds of millions to billions. That's just to break even. That means if you have a cure for a disease that 100k people have, you have to charge them each $10k just to break even.
That is insane. The numbers of course scale directly with the number of patients, too. If only 10k people in the world have the disease, you need to charge them each 100k, just to break even (the average cost of developing a new drug is actually 2.5 billion, but for these purposes let's say you get lucky and it's 'only' 1 billion).
If you want to actually make a profit, you'll need to charge even more than that.
In that case, do charity organizations that collect money to cure specific diseases or cancers actually make a difference, since their donations are supposed to go to research for cures?
I'd say that they do make a difference relative to doing nothing. It's a way of funding cures that's independent of profit, same with government funding. As far as I can tell, the only solutions to this problem are government funding and private funding of cures.
A market based solution might be allowing pharma companies to charge extremely exorbitant prices for their cures, sufficient to recoup the foregone profits of treatment. But i'm not sure how well that would go down.
Maybe it wouldn't keep a cure, once discovered off the market, but perhaps it could reduce investment in trying to find a cure to begin with? I can imagine that this wouldn't require much collusion, and there's nothing illegal about not investing in finding a cure. Even from a moral standpoint, it's a tougher argument to make.
First of all, if a pharma company had an annual income of 2bn from HIV treatments, and that companies CEO went forward with a HIV cure that is only predicted to earch 3bn overall; that CEO could essentially be removed from his position, as that would not be in the best interest of the company and shareholders.
Also, there does not need to be an evil twist where someone deliberately holds back a developed cure. It is much easier to cut/steer the research in ways that favor treatment/management options, ensuring that a cure would only be found be accident.
> that CEO could essentially be removed from his position, as that would not be in the best interest of the company and shareholders.
No. Stuff like this gets posted to HN all the time but that is just not how things work. In a public corporation, management has broad latitude to make decisions about how to run the company and shareholders have essentially no say in it. They can sell the stock if they don't like it.
If you don't believe me, consider that Tim Cook, CEO of one of the most valuable public companies on Earth, said almost exactly the same thing in a shareholder meeting and nobody batted an eye.
It's a tempting conspiracy theory, but there are a few reasons that persuade me it's very unlikely.
1. Researchers build careers based on reputation. The reputational value of "cured cancer" (even for some small subset of cancer) is probably worth more than a lifetime of developing treatments.
2. Also, some motivated researchers have lost family or friends to the diseases they're working on.
3. Also, many researchers are simply not working at for-profit companies.
All of the above can be filed under "profit is not the only motive for curing diseases (even if it's a powerful one, it's not the exclusive one)." A different tack:
4. Many lines of research have unpredictable results. Studying a virus to develop a treatment may uncover a key weakness that results in a cure. Foundational research often is too early to prioritize a use, and breakthroughs happen in unpredictable ways.
5. There are a lot of players involved in research. A big mix of for-profit companies, NGOs, and governments might have to collude to avoid developing impending cures. So if there's an reasonable next step for global research, it'd be a bad gamble for a company to avoid it, hoping that no one else would pursue it either. ie, If you can get there, assume others can too, so just claim the credit.
EDIT: OTOH if you want to run with this line of thinking, there's a great classic comedy called "The Man in the White Suit" starring Alec Guinness. He invents an unstainable suit that never needs cleaned, and the garment industry sends people to stop him.
If nothing else, many academics are motivated by ego rather than money (I'd put myself in this category). Having successfully discovered a cure for HIV would do such spectacular things for my career that the level of money that would have to be involved is pretty substantial - and would have to be spread over a large number of people.
The market size for HIV/AIDS drugs is under $15 billion [1] so while it's not chump change, it is a tiny fraction of pharmaceutical revenue (over $900 billion I believe). Like the rest of pharma, there's a fast approaching patent cliff which will free a lot of the important IP and many nations have shown they're willing to spend billions to subsidize the development of cheaper generics so I'm not sure that this source of revenue is considered reliable by pharmaceutical companies. Cancer and HIV drugs are the most expensive to develop because they are all used in complex therapeutics and I wouldn't expect many more big blockbusters either. Note also that pharmaceutical companies acquire their IP through M&A of biotechnology startups about as often as through internal R&D and biotech VCs don't have the same incentives as the conglomerates.
Furthermore, the cost of HIV drugs isn't even the majority of the cost of HIV treatment because the constant monitoring and long term complications are extremely expensive. A single hospital visit for HIV-related pneumonia or another opportunistic infection can cost more than several years worth of the drug cocktails and the visits become more frequent and expensive with age as the weakening immune system contributes negatively to almost every other healthcare issue. The incentives for public health and universal healthcare agencies around the world is pretty cleanly aligned with curing HIV at any cost.
There was a cure for Hepatitis C released last year. It's expensive, but priced below the average cost of a lifetime of treatment, so all the incentives align to get everyone to choose the cure.
This of course brings money and marketshare to the company that owns the cure over the company that owns the treatment patents, and it brings recognition to the scientists involved.
So you can take off that tinfoil hat, if someone would find a cure for HIV, they would absolutely not sit on it.
This doesn't make much sense, when very rich people (like Steve Jobs) get diseases and die. If there was a cure, at some point one of these ultra rich individuals would receive "the hidden cure" or have an overt relationship with a medical center leading to recovery. Being able to cure a disease, is generally more profitable for a generation (or more) as it's THE goto product and people are irresponsible enough that there's always new communication vectors.
This is often brought up but having had some experience in the field this does not happen. Not only would you hear a tremendous shout from the researchers themselves crying foul but the company that "cures AIDS" is going to make an assload of money and earn tremendous PR.
The real problem is not pharma trying to turn things chronic but rather people who have less common or less prominent diseases.
> This is often brought up but having had some experience in the field this does not happen.
That's not entirely true. When Hillary Clinton was running health policy in Washington, the white house threatened to impose trade sanctions on India and South Africa if they manufactured generic drugs to treat their citizens with HIV. This was before it had become an epidemic in those areas. And now that it is an epidemic, the pharma companies get tax writeoffs by working with the Clinton Foundation to provide treatment in those areas at 'reduced cost'.
When was Hillary Clinton ever running health policy? Apart from trying to implement 'Clintoncare' early in the Bill Clinton presidency I can not find any record of this.
I agree that insisting that third world countries who are already debtors to first world countries for aid pay huge sums for HIV drugs is problematic at best, but I am not sure why you add Clinton's name into this argument.
Bill controversially appointed her to be the chairperson for Task Force on National Health Care Reform, which was responsible for creating the healthcare policy for the white house. This task for is what created the Hillarycare bill.
A) That task force did not cover all health care policy, in fact it was insulated from current policymaking in order to give it freer rein to think innovatively about the future.
B) The issue you mention does not even fall under health care policy, it falls under IP and trade policy, because the point of objection is when foreign nations nullify or nationalize U.S. pharma patents. That is an ongoing fight to this day, BTW.
That's not what I was referring to. I was responding to the claim that pharmas are inclined to make treatments instead of cures in order to transform a terminal illness into a chronic one and thus make more money long term.
But with the case of HIV (and other infectious diseases), the treatment and the cure are the same drug. E.g. they could have treated people early to avoid the epidemic before it started. But instead the pharma companies lobbied the government to wait for the epidemic to take hold first, so that they could market the treatment later instead.
One could theoretically charge for a cure a little over the cost of the lifetime supply of drug cocktails, and it would still be slightly worth it for the buyer.
Of course, in practice, doing so would lead to severe media outrage, calls for regulation, state-sanctioned patent breaching all over the world, etc. So the practical price is capped. Investors know this.
wait..birth control doesn't affect STD transmission. Unless you mean people getting birth control tends to lead to mode education from the medical professionals who prescribe it to them?
It's all a statistics game. If you can vaccinate against 99% of current strains, you can severely stunt the spread of the virus with its current strain distribution. Combine this with adequate awareness about general prevention methods (safe sex practices) and you have a shot at severely reducing the incidence of the virus so that its numbers are small enough to control. New HIV infections are actually on the decline worldwide thanks to community awareness and ART meds that decrease the chances of spread.
We've been able to eradicate or nearly eradicate several viruses from the planet. It starts with getting them down to manageable numbers, then addressing every outbreak. (Granted, HIV is not quite an analagous in terms of spread to viruses like smallpox.)
The difficulty is that once you're a carrier, you're always a carrier. With modern ART these people can be expected to live long lives. ART decreases the odds of transmission, but not everyone is compliant with their medications. Reducing the spread is one piece of the puzzle. The only way we've managed to "cure" HIV is through a bone marrow transplantation from a donor that have a mutant CCR5 receptor (which the HIV virus needs infect T-cells).
I think that reducing the spread alone still could get us to a point where we "manage this out over the long term" as you say. Say you're a person with many sexual partners that has say a 1 out of 100 chance of sleeping with someone infected with HIV on a given day. Say there's a 1 in 10 chance that encounter will lead to transmission of the virus. (These aren't like factual numbers, just examples). That's still a 1 in 1,000 chance per encounter, so it adds up over time. After 1000 encounters chances are you've contracted HIV. But say you're vaccinated against 99% of the serotypes. That reduces your chance per encounter to 1 in 100,000. Even after 1000 encounters your chance of contracting HIV is 1 in 100. Not terrible.
Minor nitpick: the proportion of each serotype would determine the final reduction in your calculation above. If the serotypes in the 1% the vaccines don't work for are in 10% of the population of patients, then the final reduction would be to a 1:10,000 chance.
> Not my area of expertise but even if we can address 99% of strains, wouldn't that last 1% just take over and become the new 100% leaving us back where we started?
Not my area of expertise either, but as I understand it, it really depends on how many strains you are infected with. If it's just one, it'd reduce the infections in the next generation of patients by 99%. If the average patient had 10 strains, randomly distributed, it'd still reduce the infection rate by 90% (because there's a 10% chance of having that one resistant strain).
Only if all HIV patience had all strains (and I'm pretty sure that's not the case) would it bring us back to where we started.
You don't reduce the infection rate by 99% or by 90%, it's not even the correct term really.
The transmission rate of HIV is not really dependant on the strain but on the behaviour of the affected host.
Since HIV infection can be asymptomatic even for the natural life of a host the transmission rate is then dependant on the environment the social interaction of that host.
A host that has unprotected sex (or any other risky activity as far as blood transmitted diseases go) and does not get tested regularly will have a considerably higher transmission rate than a host that has only protected sex and gets tested when they switch partners.
Most HIV patients are infected with multiple strains, because at this point most new infections are multi-strain ones due to the lifestyle of the hosts and due to the fact that the virus can mutate in vitro.
I'm also not clear how does this press release counts "strains", since it's 16 it's more than just by major types HIV-1 and HIV-2, but then it's the question of what and how they count sub groups.
Most people in the west will get infected by HIV-1 Group M type B, type B itself can have several variations, and there are also host specific mutations, and if you are coinfected with another subtype you can have multiple variations of both and also recombinant (a new form made out of several types of the virus due to coinfection of a single cell) variations that may or may not be unique to each host.
That said effective post infection and pre AIDS outbreak treatments can drastically reduce of new hosts that end up as transmission vectors and carriers, if HIV becomes a considerably more manageable disease that would allow most infected people to carry on with a normal lifestyle (safely have sex with a partner, and have children) once treated more people are more likely to be tested regularly.
If you can also contain the disease to specific subtypes which are regionally locked as sad as it sounds you still doing quite a bit of good since now you can focus your resources on education and containment as well as further research since the transmission rates between say interveinal drug users in Berlin are considerably higher than between a sex worker in nairobi and the same drug users.
> Not my area of expertise but even if we can address 99% of strains, wouldn't that last 1% just take over and become the new 100% leaving us back where we started?
Yes, this is something to worry about and is exactly the reason why it is so hard to find a cure for AIDS. HIV mutates inside the body into thousands of different configurations and no matter what treatment you throw at it there will generally be at least a couple of strains that will survive and take over.
> Or is the promise here that we can combine this discovery with another that solves that remaining 1%?
That would be hard. There is always a chance that the additional treatment will only treat 99% of that 1% and even a single surviving virus might be enough to restart an infection with resistant strains.
> Or, do the mutations of that last 1% make HIV less virulent or harder to transmit?
One of the other comments here, from someone that read the paper, says that the antibody found in this study binds very specifically to a part of HIV that is crucial for infection so the 1% of strains that resist the antibody (due to mutations in the binding site) are less virulent. The antibody also binds only to parts of HIV that mutate very slowly so it might mean that it would take longer for virulent resistant strains to evolve.
It would seem to me that this concept of the strongest strain taking over only would happen if there were some sort of competition for resources. If you have one strain of HIV it seems weird to think that it would stop you from getting another strain and then passing both on. But "not my area of expertise" either.
First, it seems very difficult (for a virus) to transmit HIV via vaginal intercourse[1]. Second, most infections appear to start from a single virus,[2] despite the huge genetic diversity of intrapatient HIV that supposedly makes it hard to treat[3]. That means most of the strains found within one person never get transmitted. How do you manage to transmit HIV contaminated fluids but only one infection occurs in the receiving person? Very strange.
Another strange thing, it does not seem all that difficult (relatively) for interspecies transmission to occur:
"Scientists have now documented that the SIV virus has jumped from monkeys or apes into humans at least 13 separate times!"[4]
Perhaps those transmissions are due to self-injury while cutting infected meat, etc. The vagina is tissue that expects the presence of foreign human cells, and so has defenses against them. Anal sex, injections, etc are a different story. To me it sounds like an entire cell gets transmitted.
EDIT:
Another possibility is that the vast majority of these variants found floating free in the blood are non-functional and serve as chaff to confuse the immune system.
The concept is known as "vaccine escape" and is present in some viral diseases but not others. I confess I don't know how between-strain viral dynamics of HIV work, but it was definitely a concern for HPV, though it does not appear to be happening.
Most of the different variations of HIV found inside an infected person evolved inside that person from one or two initial strains they were infected with.
The various HIV strains inside the body compete with each other over infected cells. Once you kill some of the strains with a treatment it opens up space for the other strains to to fill.
