There’s now a second case of a probable true HIV cure:
Dr. Persaud [of Johns Hopkins] detailed the case of a two-year-old child in Mississippi diagnosed with HIV at birth and immediately put on antiretroviral therapy. At 18 months, the child ceased taking antiretrovirals and was lost to follow-up. When brought back into care at 23 months, despite being off treatment for five months, the child was found to have an undetectable viral load. A battery of subsequent highly sensitive tests confirmed the absence of HIV.
The physician responsible for the care was in fact Dr Hannah Gay, a paediatric HIV specialist at the University of Mississippi Medical Center. She wisely brought in the rated researchers to do the write-up, unselfishly trading a share of fame for effectiveness.
I wrote in 2009 about the first cure in Berlin: an American man, since named as Timothy Brown, with both HIV and leukaemia, was cured of both by a bone marrow transplant from a donor with genetic resistance to HIV.
Medical experts are making the usual precautionary noises about a single case needing confirmation, but it looks like a breakthrough. Maybe the baby just had an unusually strong immune system and would have cured itself anyway, but that’s not the Bayesian way to bet. Would it be ethical now to have a blind trial on HIV-positive newborns?
The good news for one child comes with two bonuses for the rest of us.
First, it’s a reminder of Lewis Thomas’ insight from 1967 (citation in the 2009 post) that treatments are expensive but cures are cheap. The marginal cost of the Berlin HIV cure was effectively €0 as they would have done the bone marrow transplant anyway. The Mississippi baby was more expensive: 15 months of the triple-drug cocktail costs around $15,000 for an adult - I guess a quarter for a baby. You have to set that against a much longer lifetime regimen, and drug prices are much less outside the USA. We also don’t know if the full 15 months was actually necessary for the knockout.
Billions have been spent on medical research since the sixties in pursuit of cures, and mostly what we have to show for it is treatments. Bruised by failure, it’s tempting for us to settle for second best, and cheaper if possible. The two HIV cures may be isolated, but they tell us not to give up hope. Victories over cancer, malaria, Alzheimer’s and HIV, not just tactical gains, are still the goal.
Second, the two cases gratifyingly show that ordinary front-line clinicians, treating single patients with discernment informed by science and carefully observing the results, can still make important discoveries. Doctors Gero Hütter and Hannah Gay are hands-on innovators in the great line of Edward Jenner, Louis Pasteur, Sigmund Freud, Isaac Luria, Barry Marshall and Oliver Sacks.
While cures are unconditionally good, bear in mind that all of the economic incentives are biased toward setting up perennial flows of revenue that can be skimmed at each step along the way.
The economic incentives for drug companies, yes. A low-risk incremental research strategy clearly has better payoffs than a high-risk one aiming at fundamental breakthroughs. But the incentives for researchers funded by the public or charities are different: these are primarily reputational, so breakthroughs are worth going for. Medical device makers? I can’t see any particular bias, though imaging and testing primarily help diagnosis not treatment.
It also depends on which drug companies. There are biotech companies working on targeted genetic modification technologies that could be applied to the bone-marrow-replacement HIV cure approach, by rendering the patient’s own stem cells immune to HIV; they have a pretty strong incentive to cure people.
I’m not an expert on the pharma industry.
But the claim that these perverse incentives inform big pharma’s choice of which drugs to pursue seems credible to me.
A new antibiotic that cures MDR TB will save millions of lives, but the expected revenue to pharma is relatively small, because the cure requires less than 100 doses, perhaps as few as 20. MDR TB patients tend not to be affluent Westerners (yet), so the price cannot be extremely high without affecting demand.
By contrast, affluent-lifestyle Western patients induced to start on a new blood pressure or cholesterol-reducing drug may be expected eventually to reliably purchase over 5,000 doses, spread over the remainder of the patient’s life — and these patients tend to have money.
If the pharma companies are the rational utility maximizers beloved of free-market theorists, we should see in the market a plethora of new drugs that mitigate but do not cure chronic conditions of the affluent, and a paucity of new life-saving antibiotics.
What do you see in the marketplace ?
Pharma may find an antibiotic for MRTB, but it will be a byproduct of the general search for new antibiotics.
I’m not sure how widely known this is, but it is true nonetheless. There are no new antibiotics in the pipeline at the moment, and there have not been since the at least the mid 1990s. Cephalosporins were the last novel class of antibiotics to be introduced. This is the first time since World War II that we have not had anything in the pipeline. This is why the development of superbugs is such a big deal. We could conceivably find ourselves back in the situation before the development of penicillin and sulfas.
Actually, this was foreseeable, and to some degree was foreseen. Evolution is real, no matter how much the religious want to deny it, and bacteria go through tens of generations per day. There are a limited number of points at which we can attack bacterial metabolisms — we particularly don’t want to attack their metabolism at a common point with ours. Eventually, we will run out of points we can attack. I don’t remember enough about bacterial metabolism to have any idea if we’ve used up the points of attack or not. Clearly, we have run out of easy points of attack.
True, and the careless use of antibiotics has accelerated the process.
However, it should be noted that, for all the medical profession’s protests, it’s not just the patients who’ve been careless. To give you an example: Both I and my wife have contracted respiratory infections over the last couple of years. Each time, we were prescribed “Z-packs”, a five day pre-packaged does schedule of Azithromycin. Why the same antibiotic every time?
Well, it’s not like they’ve made any effort At All to determine what we’re actually infected with, beyond noting that it’s bacterial. So it’s not like they could pick a particularly effective antibiotic. And I’m guessing the list of effective antibiotics is getting damn short anyway at this point, so I can’t fault them for this.
Nor do they take a throat swab, (Caveman medicine from my childhood, it seems.) to culture and find out whether the antibiotic is going to work, without the necessity of my getting worse and coming back. But I do get sicker and come back if it doesn’t work, and that probably gets them more pay from the insurance company that culturing the bug would.
But the real issue here is that they’re prescribing the exact same “adult dose” to me, and to my wife. She’s 80 lbs soaking wet, I’m nearly three times that. No wonder she gets stomach aches, and I don’t *quite* get cured. Regularly, like clockwork. She’s getting overdosed, and I’m getting under-dosed, because they’re committed to pretending all adults need the same dose.
And under-dosing is the classic way to produce antibiotic resistant bacteria. THEY are turning me into a factory for antibiotic resistance. It’s not me taking antibiotics for a viral infection, or stopping taking it partway through the prescription, it’s their own damn fault.
I’m really looking forward to the day my doctor gets replaced by a copy of Watson and some kid who gets paid the same as my oil change technician. My health care will improve immensely.
As for the impending demise of the antibiotic age, I suppose the next thing to do is start taking common metabolic weak points, and engineering them out of ourselves, so that we can use antibiotics which would have killed humanity 1.0. It would be easy enough in concept, and I think we’ll be up to doing it in a couple decades.
careless use of antibiotics has accelerated the process.
Brett and I agree.
I would go further, and immediately outlaw the practice of continually medicating meat animals with low doses of antibiotics, which is suicidally stupid over even the medium run.
I suggest the big progress here will come from the medical device people. My local pharmacy now has a simple DIY blood test machine. Its alarming results for one indicator were not replicated in a proper lab test, so the technology isn’t quite there yet. But it will soon. We can look forward to instant desktop identification of pathogens and their resistance spectra.
Brett’s right. Artificial intelligence and high-speed testing will cut human physicians out of the loop for technological medicine. GPs will be all right, as the demand for handholding is perennial, but the specialists should worry. In R&D it’s called “clinical decision support” not to scare them, but as with piloting and train driving the writing is on the wall for human attendants.
And what Joel says on feeding prophylactic antibiotics to livestock.
It certainly would be hard to run a randomised trial (blinding isn’t the main issue), but I’m pretty sure that running one would reduce the number of babies who miss out on the treatment and die of AIDS.
Remember ECMO, which looked as promising. The attempt to evaluate it without a straightforward controlled trial failed completely — a new simple trial had to be done before the treatment was accepted and used.
Maybe. But ECMO is a high-technology and on the face of it pretty risky surgical intervention, which many hospitals would not initially be technically capable of offering. There’s a large downside risk, making a trial uncontroversially ethical. We need input from someone who understands the risks of triple retrovirals in infants.