Vaccines Against H.I.V., Malaria and Tuberculosis Unlikely, Study Says | Hacker News Reader

Vaccines Against H.I.V., Malaria and Tuberculosis Unlikely, Study Says

nytimes.com

71 pointsokket63 comments

Given what I learned in recent years about the scientific process I'm always a bit wary of making this a "spend XXX money to get YYY results".

We have issues like that still a sizable amount of medical studies are unpublished because they don't produce the desired result the funder wants, that experts think a vast amount of studies are simply research waste due to poor methodology or that the majority of pre-clinical cancer studies can't be replicated. How much better could we be at tackling diseases if science wouldn't have these problems?

Sure, more funding is one part of the equation. But I increasingly get the feeling that if modern science wants to make a significant step forward they need to clean up their methodological problems. And that will not necessarily cost more, in many situations it may even cost less. (E.g. don't pay for studies that won't get published later or that are methodologically so weak that they won't produce actionable results.)

> don't pay for studies that won't get published later or that are methodologically so weak that they won't produce actionable results.

Most typically, to make studies methodologically stronger, you require a bigger sample, ie more subjects, to increase power while maintaining or even improving significance. And that would make it more expensive.

But it's uncertain whether simply pouring more money into the funding hopper would generally result in studies with larger sample sizes, or whether it would just result in a larger number of surveys with a sample size similar to the deficient ones we see today, as a larger number of scientists manage to cling by their fingertips to the gravy train. After all, there's presumably little good reason why we couldn't have fewer but better studies today, at existing funding levels.

You could be reasonable and make larger sample sizes and so on requirements.

While it isn't certain that simply pouring money into funding hoppers results in more studies, it is pretty certain that larger sample sizes (and things like this) cost more money. It is prudent to give enough for these things.

If you want to have more accountability with money, build it in. You might find it costs more or less than current funding levels - I'm going to guess costs will vary with sort of funding. Use equipment funds for equipment. Give researchers and their staff actual, decent, steady wages not reliant on results. (A "negative" result isn't negative, after all, for it disproves something).

And so on.

I spoke to a medical researcher who had worked both in public and private labs during their career, they said when they worked in public academic labs there was incompetence to the extent that no-one understood how to properly calibrate certain lab equipment. Working in private research, they said public research generally could not be replicated, and unless from a known lab was considered borderline useless.

I think it goes way beyond what you’re talking about. In large sections of academia there’s a very Darwinian system where researchers are fighting for their careers and labs are trying to keep their heads above the water, and everyone needs sexy results now. I don’t think such a system can lead to robust, unbiased research by default.

There needs to be a journal for negative results.

>We tried X it didn't work.

Would be invaluable in a lot of fields where knowing what's been tried is more important than knowing what hasn't.

Can anybody briefly describe how a 3x funding increase would change things from "may not be able to invent" to "[likely] to be able to be produced in the foreseeable future"? I'm very disappointed that news articles no longer hit on even the most fundamental questions like this. Instead articles now take a position (you should be in favor of donating money to [x,y,z]) and then go from there.

This seems to challenge belief. There are almost always rapidly diminishing returns on increasing allocation of resources once you reach a certain baseline. And almost is a weasel word there -- I can't think of anything where this is not true. Just like 50 programmers won't work 50 times faster than 1 programmer on a given task, 50 times the amount of money dedicated to a task will often provide far less than 50x the return. And the article's premise is suggesting not only a linear return on investment, but a largely exponential one.

Of course this all goes out the window when you're desperately understaffed or underfunded, but if $3 billion a year is anything remotely close to 'desperately underfunded' then it makes one wonder if that may be a product of waste and inefficiency than a lack of funding.

For some science, the baseline is very high. You can't do X-ray crystallography of organic compounds, for example, without a synchrotron.

Absolutely, but I think we become desensitized to numbers. $3,000,0000,000 is alot of money.

In trying to find the costs of a synchotron I came upon this article [1] that mentions the construction of an entire campus surronding a synchrotron, experimental facilities, and so on. The entire construction project and synchotron cost £263 million. That's at government level efficiency, which is to say significantly overpriced, and of course is also just a one-time expense. Even this one time inefficient cost however is only about 10% of our annual spend. The ongoing spend related to maintenance of the facility would of course be a small fraction of that upfront cost.

I just don't understand how one can argue that a 3x increase in funding can be expected to yield massive exponential gains in output.

[1] - https://www.theage.com.au/national/synchrotron-will-cost-tax...

It’s $0.5 per person.

That's great in a single-variable universe, but in ours unfortunately there are a million other "it's (only) $0.5 per person" things. It's like letting the public choose what students have to learn - "but this is sooo important!" (and this, and this, and this,...).

I don't understand that kind of argument. You have to choose the right level of scale for what you are looking at. I would not trust an architect (of buildings) who is a particle physicist, or a forest(-system) manager whose specialization is the cell. Some things need to be looked at the the higher (compound) level to get any useful results.

EDIT (for the reply below, to which I cannot reply?):

> I find it important / useful for myself to put it into context.

Well, my point is that you don't.

It’s both a lot of money and also much less. I find it important / useful for myself to put it into context.

For me the takeaway is that I went and calculated how many times richer than the average and therefore what my share of $0.5 per person would be. It still wasn’t a lot. And probably more affordable to me than the person at the middle of the income scale even then.

But yes! I see the “what about all the other things” element too.

DNA's structure was deduced from X-ray crystallography using a conventional X-ray tube, most laboratory protein crystallography doesn't require a synchrotron light source.

Here's a typical unit:

https://www.rigaku.com/en/products/protein/micromax007

The MicroMax™ 007 HF is the most widely used home lab X-ray source for protein crystallography and a popular source for small molecule crystallographers who need the additional flux of a rotating anode generator.

Yow. I thought I had a pretty hardcore home lab with my Faxitron cabinet machine.

Sorry, I meant lipid-phase organics. In any case, it is true that some science has huge initial investment cost - synchrotrons, space telescopes, etc

Look at all the money thrown into all of wars. Not just the longest-running war in history in Afghanistan and the War on Terror. But the War on Drugs. War on Poverty. What about global warming--how much money is thrown into that? Are we really making progress. Meanwhile every day I see homeless people on the streets, and read about stories of police murdering, beating, or swat raiding innocent people over nothing. How far could giving a little bit of that money to protect people's supposed rights to life and liberty go? Isn't that what we are supposedly going after, anyways? Or do we just donate to who causes based on other factors. Such as who has the best fundraising? The best lobbying? Or the cause that people with money personally care about?

Future generations are going to look back at us like we are psychopathic barbarians.

>> longest-running war in history

https://en.m.wikipedia.org/wiki/List_of_conflicts_by_duratio...

In US history, sorry it made sense as implied when I was typing it.

A lot of money goes into taking a good idea for a vaccine to syringes ready to deploy. The actual study goes into the real detail:

https://gatesopenresearch.org/articles/2-23/v2

> This seems to challenge belief. There are almost always rapidly diminishing returns on increasing allocation of resources once you reach a certain baseline. And almost is a weasel word there -- I can't think of anything where this is not true. Just like 50 programmers won't work 50 times faster than 1 programmer on a given task, 50 times the amount of money dedicated to a task will often provide far less than 50x the return. And the article's premise is suggesting not only a linear return on investment, but a largely exponential one.

I see research, especially fundamental research, like a lottery in which we don't know what we will win. State invests X billions of dollars, and a breakthrough will likely happen, but maybe not in the expected problem (principle of serendipity). More X billions means a higher chance of breakthrough, and hopefully on the desired problem. Surely experts and thinkers looked at efficiency in research, but by definition researching is about looking at the unknown, and when there is uncertainty, a lottery model is probably a better way of thinking about it.

There is already prep, a once a day pill that if taken consistently, is over 95% effective at stopping HIV infection, I've heard some sources say it's 100% effective. While it's not medically considered to be a vaccine, most vaccines for other conditions have a lower effectiveness rate.

There is work being done to turn prep into an injectable chip in the arm, like long term contraceptives, but for HIV prevention.

Can you point us to a source regarding this pill? Is it in clinical trials?

You must be North American, it has been in broad use for years: https://www.cdc.gov/hiv/basics/prep.html

This is a medication that’s far beyond the clinical trial phase and is widely available in many countries, though still subject to some large-scale trials for this particular usage. There’s lots of information on sites like https://www.iwantprepnow.co.uk - it’s available through the healthcare system in some parts of the UK, purchasable privately in others, and from what I understand available on some insurances in the US.

It’s a combination of two antiretroviral drugs also used in HIV treatment (Tenofovir and Emtricitabine) and the effectiveness of it can’t really be overstated - my understanding is that there are only two documented cases of someone correctly using this drug becoming HIV-positive, and in both cases due to rare strains with resistance to both drugs.

It’s not a vaccine, but it does change the picture massively for at-risk groups.

> and in both cases due to rare strains with resistance to both drugs.

So then it is only a matter of time before we have 'super' HIV strains that are resistant running around. Perhaps it's not such a great idea to have large numbers of people exposing these drugs to the virus regularly, else we'll end up with more resistant strains..

I'm not a virologist, but my understanding is that the lifecycle of HIV makes that unlikely. An individual must be infected with the virus in order for drug resistance to emerge; using PReP prevents infection from happening in the first place by stopping viral replication. HIV is quite hard to transmit – someone who is not infected or who is on a stable treatment regime can't transmit the virus to anybody, so resistance isn't much of a concern there.

The bigger risk of drug-resistant strains emerging is due to poor adherence to medication regimes. Missing doses of antiretroviral therapy can cause drug resistance to emerge rapidly, as viral replication is no longer suppressed and HIV mutates like crazy.

So what are you suggesting exactly, an end to vaccines? What makes HIV any different?

That is not a vaccine... No antibodies are created by the body to attack HIV. There's a big difference.

In the US it is marketed as Truvada (https://www.truvada.com/) which is the combination of drugs used. Approved by FDA in 2004.

PrEP sold under the name Truvada in the U.S. I actually saw a TV commercial for it earlier today.

https://www.cdc.gov/hiv/basics/prep.html

The thing that worries me about antiretroviral drugs is that they mess with mechanisms that are innate to the reproduction of cells.

Their effects can, e.g., be clearly seen in changes to the bone marrow, which IIRC has some of the fastest-reproducing cells in the human body.

We don't have long-term data yet on what this does to users of this drug.

My wife has to take such drugs as she has HIV, and I wouldn't be surprised if it ended up shaving a few years off her life expectancy. She's fine now, but who can predict the cumulative effects? Of course, since without the drugs her life expectancy would be drastically lower, she obviously takes them, and they are a godsend.

But I'm kinda waiting for the other shoe to drop.

What I'm saying is: it's great that we have this option, and it should be used where it makes sense. However don't think that this medication frees you from worry in the same way vaccinations typically do. The tradeoff is much different.

It's true that there are definitely some side-effects and we'll need to wait and see what the long-term consequences are. The good news is that they at least appear to be well-tolerated drugs, and newer drugs show fewer adverse effects - minor bone-density reduction and renal function impact are the main adverse effects of Tenofovir + Emtricitabine, with no obvious effect on bone marrow for example.

But it's quite a tricky decision to make. Vaccines aren't without risk either, though adverse reactions are also rare. Certainly from a cost perspective, PReP with high efficiency makes a lot of sense – lifetime treatment and monitoring of an HIV+ patient can be markedly more expensive than a relatively cheap preventative medication, especially in high-risk groups.

I have been beating around the idea of taking PReP for a while, what with being part of a higher-risk group in an area with relatively high HIV prevalence. It's definitely a harder commitment to make than vaccination is, but I hope that we can improve our knowledge and understanding of the risks as the trials currently underway progress.

I will note that since these are "diseases of the poor," a valid approach would be to eliminate poverty instead of assuming it will always be with us.

You can't ever eliminate relative poverty, which is about "keeping up with the Joneses". But you can make real progress on absolute poverty. This is a fundamental difference between developed and developing countries.

We need to do this anyway to address the growing issue with antibiotic resistant infections.

The title of the article seems to suggest no vaccines are available for these diseases, but at least in the case of tuberculosis there is one [1]. The article does refer to it:

“The foundation still hopes to show that booster doses of BCG, a century-old childhood tuberculosis vaccine, can protect adolescents and that a vaccine candidate it is developing with GlaxoSmithKline, the pharmaceutical company, will stop latent tuberculosis from becoming active.”

[1] https://www.cdc.gov/tb/topic/basics/vaccines.htm

BCG has its own issues, though. Immunity wanes after awhile, the protection is incomplete and it seems to be more effective at preventing extrapulmonary disease than pulmonary.

This by no means says it's useless. It has probably greatly diminished pediatric tuberculous meningitis in at-risk counties, which can be devastating (one of my nightmare cases was a two-year-old who lost part of his occipital lobe to contaminated dairy). In low-prevalence countries, however, where pulmonary TB is the primary concern, its utility is questionable.

https://www.cdc.gov/tb/publications/factsheets/prevention/bc...

AIDS/HIV seems largely containable through PReP. I don’t know if long term pervasive but not universal use of PReP by those at risk would eventually lead to resistance to the medications used, though.

Malaria probably can be eliminated for single digit millions of dollars through gene drive against specific species of mosquitoes which carry it.

TB scares me, mainly due to high risk populations and XDR variants.

Yeah, while we may never win the war against HIV and Malaria, we will continue to make progress towards prevention and treatment, and they will become less and less of an issue with time.

With TB we seem to be losing on both of those fronts, and it is indeed something to be scared of...

We cannot stop AIDS/HIV research until gay sex is just as safe as hetrosexual sex. Much higher priority than malaria according to where the money is being spent....

Sure, because HIV through heterosexual sexual relations, needles, mother to child, and other types of bodily fluids exchange definitely aren't a thing. Let's go back 3 decades and call AIDS "GRID" again.

Even if AIDS went away overnight, there would still be a whole range of other diseases spread particularly through male homosexual sex, IV drug use, and high-partner count or professional sex. I wonder at what point hepatitis actually becomes more of a problem in rich first world cities than HIV.

>there would still be a whole range of other diseases spread particularly through male homosexual sex

Like what?

Hepatitis, especially correlated with HIV fear being reduced due to PReP, and decreased use of condoms.

I believe a lot of other STDs and diseases caused by STDs (anal cancer from HPV) are prevalent in certain communities at higher rates. It is a good argument for increased targeted education and health resources for those communities, both to help them and to reduce spread.

>Hepatitis

This isn't limited to homosexual activity and is far more prevalent in exclusively heterosexual "populations." In fact, there isn't a correlation between any kind of sexual spectrum (though there are sexual activities that increase risk of infection, male or female partners). It just is. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1195276/

Where are you getting your information from?

>HIV fear being reduced due to PReP, and decreased use of condoms.

As a Western homosexual (there are more heterosexuals in the world with HIV than homosexuals), this is a concern. But it's largely about HIV resurgence. Condoms can help prevent a whole host of STI's/STD's so it's always just good practice, and one that's been waning lately due to lack of education, community reinforcement because of the former, and people thinking everyone is on PReP. And of course, HIV isn't the death sentence it once was.

As far as other STD's go, you'll need to provide some data in regards to those diseases specifically impacting the homosexual community.

There of course isn't one global homosexual community, but SF public health and other targeted information is what I see the most of. It may be biased just because it's pretty well funded and relatively well executed, but as someone without particular interest in STDs, it's what I see the most information about.

e.g. https://josephsciambra.com/increasing-rates-of-all-stds-amon...

https://www.sfdph.org/dph/files/reports/StudiesData/STD/SFST...

http://www.sfcityclinic.org/providers/PromotingSexualHealth_...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034619/

Re: Hepatitis: https://www.cdc.gov/msmhealth/viral-hepatitis.htm

In general total number of infected persons is probably not as meaningful a metric in terms of transmission risk for a member of the population as rate per 100k or rate of new infections per year per 100k in a group. There are a lot more heterosexuals, non-IV-drug-users, and non-professional-sex-workers in the world. It's also possibly worth normalizing rates based on age cohort or number of sexual partners, relationship status, etc.; a monogamous gay couple of 20 years is essentially certainly of lower STD risk than a heterosexual with multiple new partners per year. But as a population, certain populations do tend to engage in a constellation of riskier behaviors, and have higher incidence of disease and of new infection.

Of course a decrease in condom use would most likely yield an increase in STD rates in any community. I'm having trouble discerning which source supports this:

>are prevalent in certain communities at higher rates.

You then seem to switch your perspective in the comment I'm replying to:

> total number of infected persons is probably not as meaningful a metric in terms of transmission risk

Which I would agree with, but you're not even addressing it. And of course the obvious needs to be said, the total number of people effected is needed to to ascertain which STD's "are prevalent in certain communities at higher rates." I'm still trying to figure out which STD's (besides HIV in the Western hemisphere), you're talking about.

Also if you're going to source stuff could you be bothered to not link to opinion pieces that are just a collection of cherry-picked quotes? There was no data or real scientific hypothesis involved. It was an opinion piece from an author who has quite the record on fighting LGBT+ rights. In fact there are two authors who clearly have a religious context to their arguments, a context that is detrimental to any rational conversation about this subject. It's well understood that such attitudes affect care and treatment, and the willingness to seek out care and treatment for young LGBT+ people. At best it's just non-sense, at worst such authors are actively helping the problem stay around.

1) "About 10% of new Hepatitis A and 20% of all new Hepatitis B infections in the United States are among gay and bisexual men" (CDC, https://www.cdc.gov/msmhealth/viral-hepatitis.htm) -- that's a much higher number than the incidence of gay and bisexual men in the overall population of the US (2-5%?).

2) "Gay and bisexual men and other men who have sex with men have the highest prevalences of gonorrhea, chlamydia, and early syphilis." (SFDPH, https://www.sfdph.org/dph/files/reports/StudiesData/STD/SFST...)

3) "Men who have anal sex with men (MSM) are more likely to get anal HPV than men who only have sex with women. Researchers estimate that the prevalence of anal HPV among men who only have sex with women is around 15% while anal HPV prevalence for MSM is around 60%." (https://betablog.org/anal-cancer-hpv-gay-men-need-know/ which references http://jid.oxfordjournals.org/content/203/1/66.full.pdf+html)

>that's a much higher number than the incidence of gay and bisexual men in the overall population of the US (2-5%?)

1) A valid insight, but misdirected. The prevalence rate is still higher in heterosexuals. You'll find a common point in many medical texts that a lot of what happens in the homosexual community, disease wise, is due to how small it is. A smaller network makes it easier/faster for every node to get the message.

>Gay and bisexual men and other men who have sex with men have the highest prevalences of gonorrhea, chlamydia, and early syphilis.

2) Right, in San Francisco. Not world wide.

>Men who have anal sex with men (MSM) are more likely to get anal HPV than men who only have sex with women.

3) This isn't surprising, since homosexuals definitely have more anal sex than heterosexuals. You should compare this to general HPV rates.

I am still awaiting support for your original claim about homosexual sex.

There are more heterosexuals with HIV than homosexuals.

This are some amazing buzz words your have learned.

"Malaria probably can be eliminated for single digit millions of dollars through gene drive against specific species of mosquitoes which carry it."

Probably. And to throw a mutagenic chain reaction against evolutionary pressure, what possibly could go wrong? And why does this not work in the lab and why do mosquitoes develop resistance against gene drive after a few generations?

It never ceases to amaze me how easy people like HN User "rdl" believe fixing Malaria is. They think we can just wave a magic wand, and all of a sudden the world would be rid of Malarial disease. Do they think idiots have been working on this problem for the past 2 or 3 hundred years? Malaria is one of the most savagely cunning bugs around. Given the history of our fight against it, to imply that we are going to get rid of it with a bit of genetic pixie dust is just astoundingly naive.

Just like we got rid of smallpox with (initially) cowpox pixie dust? Or are very close to getting rid of polio with vaccine pixie dust? (Massive amounts of work to deploy each of these to the entire affected populations, but at core the technology is what makes it possible.)

Don't bother arguing with these trolls .... they seem woefully ignorant of just how fast things are moving in the lab, particularly with the sudden explosion of genomics and high throughput screening.

Dude, I possible working with HTS before you were born.

Is also unlikely given if everyone gets vaccinated, drug companies lose hundreds of billions, they are likely to buy out and bury such endeavours. Someone tell me I’m wrong to think that way.

The recent Hep-C antivirals (Sovaldi & friends) should be a counterargument. With a course of medication you actually cure Hepatitis C. Previously you'd be looking at a liver transplant and taking immunosuppressants for the rest of your life.

This article is seriously lacking. For example this: https://www.hiv.gov/federal-response/funding/budget says:

"With the generous support of the American people, the U.S. government has annually committed more than $6.6 billion to bilateral HIV/AIDS programs, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and NIH international HIV research."

And yet the entire world spent 3B on all vaccine research combined, of which the US alone spent half?

The numbers are not adding up, unless most of the research is not for a vaccine, and if that's the case the article should have said so.

> unless most of the research is not for a vaccine

This. Only a small sliver of that would be for vaccine research, probably at a handful of labs.

So under the assumption that the researchers involved are smart people, they believe that this is the best use of the money.

So why should I believe a random article that increasing specifically vaccine spending is the right thing to do?

If it's only a small sliver, them to get the massive increase the article wants, total spending must go up massively. Either that or the researchers are not directing their money in the right proportions, which seems unlikely to me.

Whatever the correct situation is, the article is seriously lacking for not even mentioning any of it. And if that's the case, I am inclined to disbelieve the entire thing.

Researchers are usually bright people, but funding is often decided by entirely different people, and policy. But anyway ...

Vaccines, as well as antibiotics are hard to find/make and eithee have high price sensitivity, nobody will pay a million for a dose of vaccine, or as with new antibiotics, will only be used as a last resort to combat bacterial resistance. As most medical research today is made by for profit companies, less money is spent on things that are harder to make money on.

Many 'easy' vaccines are already done, and the same goes for antibiotics, so there is. need to move public funding into the entire pipeline for these kinds of substances. Almost forgot, antivenoms also suffer from this, mostly because there are many venoms, and few victims.

The budget comes from desperation, which is unaffected by futility. Researchers are well aware that funding goes to those who claim that there is hope. Voters demand that we do something, and throwing money at a doomed cause is something, so therefore we must do that.

... and my point is proven by the downmods: nobody wants their hopes crushed, no matter how unjustified

Budgets also come from perceived market demand. Is the market for HIV maintenance products bigger or smaller than the market for HIV vaccination drugs?

(Cynically I'd remark a one-off HIV vaccine shot would eliminate the need for lifelong maintenance drugs, and shareholders get the best returns with that latter...)

At least for HIV/AIDS & TB, a widely available and a sure cure would be great. Of course nothing beats the efficacy of vaccination.

TB is very curable in most cases. The problem is it takes a long time, the regimens can be difficult, and active cases become resistant if they're not monitored (why we use directly observed therapy), and latent cases with the typical treatment take just about as long.

What we really need for TB are shorter high-efficiency regimens. These would be done quicker, leave less opportunity for drug resistance, and make progress on today's latent cases which are tomorrow's active cases. The newer 3HP regimen reduces latent treatment to 3 months instead of six to nine, but we really need to get it down to weeks or less.

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