This Drug Could End H.I.V. Why Hasn’t It?


robert grant

So I chose to pursue a career in science because I believed at some deep level in the transformative power of discovery, that scientific discovery, learning something new, can transform our world as we know it. And yet over my 35 years, there’s only been a few opportunities where I could really feel how that is true, and one of those moments is when I learned the results of our clinical trial that I’d been working on for eight years that was aiming to prove that a medicine taken before and after sexual exposure would be effective and safe for preventing acquisition of H.I.V. And so we knew that we were about to learn whether all of that work was leading to yet another failure in the H.I.V.-prevention field or whether we had discovered some new way of preventing H.I.V. So I gathered in this windowless room in Bethesda on the N.I.H. campus. Several of us had traveled, in some cases from places as far away as Peru, to be there. We were sitting around a table with our study sponsors, the investigators, the statisticians. There was maybe 10 or 15 of us. And we walked through the data, and we heard for the first time that people who had taken the drug did not get H.I.V.-infected. There was a round of applause. They just — they clapped. There was nothing to say. People were stunned. I think people realized that everything was different, that everything was changed.

archived recording 1

Scientists are celebrating what they’re calling a major breakthrough in the fight against AIDS. A new study finds taking a drug called Truvada before exposure to H.I.V. reduces the risk of infection in gay men by up to 73 percent.

archived recording 2

This is the first time a study has been done that shows that taking a drug before exposure to H.I.V. can prevent infections.

archived recording 3

I think that we are in an era now for the first time when we can foresee the end of the AIDS epidemic.

michael barbaro

From The New York Times, I’m Michael Barbaro. This is “The Daily.” Today: Dr. Robert Grant developed a treatment that could finally solve the H.I.V. crisis. Why it hasn’t. It’s Wednesday, June 5.

robert grant

As I was graduating, I remember talking to the dean of students. And he says, well, what do you want to do with your medical career? And I said, well, I’m going to work on H.I.V. research. And he says, oh goodness, Bob, don’t do that.

robert grant

Well, he said, by the time you’re fully trained, the epidemic will be over. To this day, I don’t know if he was overly optimistic about how long it was going to take for the epidemic to end or whether he was overly pessimistic about how long it was going to take me to be fully trained. In either case, I just became really clear that this was O.K. with me. If the epidemic ended tomorrow, I would retire and go fishing and tell stories about how there was a deadly disease that was among us for a while and disrupted our connections and our sex life and killed people when they were young for no reason.

donald g. mcneil jr.

After years of doing research in the early 2000s into treating H.I.V., he turns his focus to trying to prevent H.I.V., and the concept he comes up with is pre-exposure prophylaxis, or PrEP —

michael barbaro

Donald G. McNeil Jr. has been covering H.I.V. for decades.

donald g. mcneil jr.

— which means taking one pill of H.I.V. medicine per day, a small dose, to prevent you from getting the disease.

robert grant

You know, I remember, you know, saying, well, the next big task here is a vaccine. We need an H.I.V. vaccine. And yet, try after try, the vaccines for H.I.V. were not proving to be effective. And that’s when, I think, many of us became interested in the possibility that the same antiretroviral drugs that were good for treatment could also be used for prevention.

donald g. mcneil jr.

So he puts together a trial and eventually gets funding for it from the federal government and the Bill and Melinda Gates Foundation.

robert grant

Our initial proposal was to use a medicine called tenofovir.

donald g. mcneil jr.

Tenofovir is a drug that, under the brand name Truvada, was already being used for H.I.V. treatment. He wanted to see whether or not it would work for H.I.V. prevention. And the drug company that makes it was willing to donate enough doses for the trial.

robert grant

At that point, we chose to study Truvada for PrEP.

donald g. mcneil jr.

Dr. Grant got the impression that Truvada would soon be out from under patent protection.

michael barbaro

And what made you believe that, that it would be going off patent?

robert grant

Well, it had been invented in 1985. There were colleagues, friends at Gilead who said, don’t worry about it. By the time your research is done and it’s proven that PrEP is effective, the drug would be off-patent.

donald g. mcneil jr.

Which meant that the generic companies would enter the market and make cheaper versions available soon, and that’s one of the reasons he chose that drug for the trial.

robert grant

That was what I was led to believe. That’s what I led my study sponsors to believe, and it seemed clear that by 2010 the medicine would be available in generic form.

donald g. mcneil jr.

I’m not quite sure how he got that impression, because Gilead argues that its patents last until 2021 on the drug, but every drug is covered by multiple patents. You can patent the chemical, the process for making the chemical. You can patent dosages. You can patent delivery forms, you know, pill versus patch, things like that. So there are many, many ways to patent a drug and keep your exclusive right to be the only marketer of it. And so Dr. Grant begins a trial in around 2002.

michael barbaro

So this clinical trial is being paid for by the federal government, by taxpayers —

donald g. mcneil jr.

That’s right.

michael barbaro

— and private foundations, not by the pharmaceutical company that makes this drug, not by Gilead.

donald g. mcneil jr.

That’s right.

michael barbaro

And Gilead simply donates the medicine to be used as part of this clinical trial.

donald g. mcneil jr.

That’s right.

michael barbaro

So he intentionally works with Gilead for, among other reasons, the idea that this drug at the end of all this, if it worked, would be available in a relatively inexpensive way to lots and lots of people who might need it.

donald g. mcneil jr.

In theory.

robert grant

We were able to recruit 2,500 people in 11 sites in six countries.

donald g. mcneil jr.

The trial lasted eight years, and it was a huge success.

robert grant

What we found is that the people who had received the active form of the drug had much lower H.I.V. infection rates. And if they actually took the medicine daily, no one got infected.

michael barbaro

So then the trial ends. It’s a success. They’ve shown that when people take this drug every day, the vast majority of them don’t get H.I.V. What happens next?

donald g. mcneil jr.

Everybody assumed now men are going to be on it. In the United States, they’re all going to be on it immediately. That doesn’t happen.

donald g. mcneil jr.

As far as I can tell, two reasons. One, Gilead didn’t advertise it. And they never explained why, but the obvious reason is using a drug as a preventative is different from using it for treatment. When you treat somebody, they’re already sick, so they’re not likely to sue. When you give a drug to somebody who’s healthy, if they happen to get sick anyway, they might sue. The other huge reason people didn’t get on it en masse is the price.

michael barbaro

Tell me exactly about the pricing.

donald g. mcneil jr.

I think it was around $14,000 a year when this new use started, and then the price has risen up to pretty close to $20,000 a year.

michael barbaro

That’s a very big price tag.

donald g. mcneil jr.

Yeah, it’s a high price, and it’s a high profit margin because we know that it only costs less than $60 a year to make.

michael barbaro

So something that costs $60 a year Gilead is charging upwards of $14,000 a year for.

donald g. mcneil jr.

Correct.

michael barbaro

Well, that’s almost $14,000 in pure profit.

donald g. mcneil jr.

That’s the way the drug industry works in this country. Most chemicals don’t cost all that much to make. Once you’ve got a giant factory-sized process line going, many of these drugs can be made literally for pennies a pill. But because they’re patented and nobody else can sell them and the seller can name his price, they name what they think the market can bear.

michael barbaro

So what kind of response has there been to the high price of Truvada?

donald g. mcneil jr.

The high price of Truvada keeps people from getting the drug because to get over the high price or to get somebody else to pay for the drug for you is an enormous bureaucratic hurdle. You’ve got to either do it through your insurance company, or if you’re not on Medicaid, you’ve got to get on Medicaid. If you’re not on Medicare, you’ve got to get on Medicare. Really, there ought to be a million people on this drug in the country. That’s the number of people who are at high risk of getting H.I.V., and now there are only about 270,000 people in the country. That’s a tremendously underserved market for a very effective thing that acts like a vaccine.

robert grant

I’m devastated that only 14 percent of people who could benefit from PrEP are getting it in the United States, and I’m devastated that the H.I.V. transmission rates nationwide have not decreased since 2013. This was 20 years of work and risk and effort to end H.I.V. transmission, and we all know that it can happen if we actually use treatment and use PrEP, but it’s hard to use at a price tag of $2,100 per person per month. It does not matter if it’s not used and if it’s not available for everyone who needs it, and it does not matter unless we can use it to end H.I.V. transmission.

archived recording 1

This initiative is designed to make sure all people get access to PrEP and comprehensive prevention service.

archived recording 2

Then why are we [INAUDIBLE] the dollars on the table? The programs need more money. Give them more money.

archived recording 3

And it’s terribly expensive, and I think we really need to have a conversation as a community about how we’re being taken advantage of by the drug companies and, in particular, Gilead.

archived recording 4

The C.D.C. has a legal right —

archived recording 5

Why didn’t you tell us about it?

archived recording 6

Gilead, your price gouging is killing people. Your price of Truvada is so high that people in the U.S. cannot afford it.

archived recording 7

So we have additional questions that have come from all of you, and I know you want to hear them.

archived recording 8

No, we have recommendations. [APPLAUSE]

michael barbaro

We’ll be right back. So what has Gilead’s response been to this call to make this drug cheaper, and therefore more accessible?

donald g. mcneil jr.

The two things Gilead’s done in response is they have announced that a generic company will be able to enter the field one year earlier than expected, in 2020 instead of 2021. And just a few weeks ago, the Trump administration announced it had reached a deal with Gilead for Gilead to donate to 200,000 patients anywhere in the country.

archived recording

The Trump administration announced Thursday that Gilead Sciences, which manufactures Truvada, plans to donate the drug for as many as 200,000 people for up to 11 years.

michael barbaro

How big a deal are either of those? How meaningful are they?

donald g. mcneil jr.

Having generic competition one year earlier means that the process of the price dropping will start one year earlier. It probably won’t be instantaneous. It usually takes four or five generic companies entering the field before the price really drops substantially, and that may take longer. And 200,000 free doses is an important move, but the AIDS activists are suspicious of this move.

michael barbaro

Why are they suspicious?

donald g. mcneil jr.

Because of the terms of the deal. Roughly a million people need the drug. Only about 250,000 are on it. So it’s not going to cover everybody who needs it, and most of the people who need it are poor, gay black and Hispanic men who are not very well connected to the medical care system. The deal is only for 11 years, and this is a drug you need to take for life. But the other part of the deal that makes the activists most suspicious is the fact that in the middle of the donation, everybody will be switched over from Truvada to Gilead’s new drug, Descovy, as soon as it’s approved for PrEP. Descovy is a slightly different form of tenofovir that supposedly has fewer side effects, although tenofovir is a relatively safe drug and Descovy has some side effects of its own. The fear that the activists have is that people are going to start demanding Descovy once they’ve been switched on to it, and Descovy is now patented for the next 20 years, and Gilead says it’ll price it for 20,000 bucks a year. They see this as a way of creating a market for Descovy.

michael barbaro

I think I’m starting to understand. So to activists, this feels a bit like a bait and switch. It’s kind of insidious in the sense that it’s not nearly enough pills to help everyone who needs it who can’t afford it, and it’s creating a kind of financial pipeline to a new version of the drug.

donald g. mcneil jr.

Bingo. If they get used to taking Descovy for two or three years and then the donation runs out, then they’re going to clamor to stay on Descovy even though the federal government’s going to say, wait a minute, we’ve got really cheap Truvada here, so we want to put you on that. It’s making a market for a new drug that otherwise would have cost them a lot of advertising money to create, and it’s drying up the demand for generic Truvada because nobody’s going to want it anymore. Donating the Truvada costs them almost nothing because we know that it costs less than $60 a year to make, so the activists estimate that that donation is costing them less than $10 million a year. But they’re taking a tax deduction for something like the retail cost, not the cost of making it. That’s how donations work for the pharmaceutical industry. You donate something that costs you pennies to make, and you take the tax deduction for the dollars that you sell it for.

michael barbaro

So Gilead is theoretically making money in this donation, possibly.

donald g. mcneil jr.

I’m not with the I.R.S., but in theory, yeah. But the larger picture is that this is part of the Trump administration’s goal to help end the H.I.V. epidemic, which helps American citizens, but the activists fear that the result of it is going to be helping a drug company increase its profits.

michael barbaro

Is this a novel strategy, to donate drugs like this?

donald g. mcneil jr.

No, it actually echoes something that happened 20 years ago, when AIDS was ravaging Africa.

archived recording

More than 35 million people around the world have AIDS, and about two-thirds of them are African. The death rate in Kenya is more than 500 a day.

donald g. mcneil jr.

H.I.V. drugs cost $15,000 a year. The drug companies did not want to lower their prices. Originally, they completely turned their back on Africa and let people die because they were charging those prices, and there was an enormous outcry.

archived recording

This is a crime. You cannot have 40 million people dead and then more dying every year, and then the issue should be about money.

donald g. mcneil jr.

It seemed incredibly immoral for them to ignore the market, but their first offer was to give a certain number of free or deeply discounted drugs into the market, basically in order to make themselves look good. And if you can give enough free drugs into a market, you dry up the demand, and that keeps everybody quiet because there’s no need, no incentive, for the generic makers to get into it.

michael barbaro

Because the pills are already there.

donald g. mcneil jr.

Right, because the pills are already there. And meanwhile, you’re getting large tax deductions for the pills you’re giving away. So if you can keep them out of the market, you kept an entire world of competition out of your field.

michael barbaro

So what Gilead is doing with this donation is actually following a pretty well-worn playbook, just doing what pharmaceutical companies have long done before, actually, in the course of the H.I.V. epidemic, so maybe no one should be all that surprised that that’s how this played out.

donald g. mcneil jr.

It’s one of many market-protecting plays that the drug companies have learned to use, yeah.

robert grant

I realize now that I was naive. Everywhere I went, people would raise the concern that PrEP is never going to be inexpensive enough to actually use, and that the price is always going to be high. And I would assure people that, one way or another, we will find a way to lower the price to what it can be and should be. And what I regret is that I feel like I left that promise without staying involved enough to make sure that we made good on that promise. And when I discovered just last year that the price has been increased year after year and that so-called efforts to make this available to everyone who needs it are half-hearted, I said, look, this is not correct for me. I need to get back into this and stand by the promises that I made that we will find a way to end this epidemic. And so at one point I got a call from the House Oversight Committee’s staff, and they wanted to hear me talk about my story, and I told them. And about a week after that, they invited me to the hearing.

archived recording

I now want to welcome our witnesses. Dr. Robert Grant, professor of medicine at the University of California, San Francisco.

donald g. mcneil jr.

So Dr. Grant goes and testifies before Congress a few weeks ago.

archived recording (robert grant)

I devoted the last 20 years of my career to the development of PrEP. I am here today at my own expense because I promised that PrEP would become available if proven. We have not kept that promise. I come today to ask for your help.

donald g. mcneil jr.

And he basically asked Congress to step in, arguing that Gilead has essentially made it impossible for an affordable version of the drug to get to market.

archived recording (robert grant)

In my experience, the root cause of low PrEP access is the high price.

donald g. mcneil jr.

And the Gilead C.E.O. was also there testifying and answering questions from Congress, and Alexandria Ocasio-Cortez from New York asks about the price in other countries.

archived recording (alexandria ocasio-cortez)

So the list price is almost $2,000 in the United States. Why is it $8.00 in Australia?

archived recording (daniel o’day)

Truvada still has patent protection in the United States, and in the rest of the world it is generic.

michael barbaro

So Donald, on paper, this feels kind of sinister, but isn’t this just how the system works in this country? A pharmaceutical company has the right to defend its intellectual property, its investment, its years of work in creating these drugs, no matter how much they actually technically cost to make each pill, and that’s just how our market system functions?

donald g. mcneil jr.

Yes, they’re playing by the rules, but they help make the rules. And the big example of that is that in this country, unlike any other country, federal agencies that buy drugs from the drug companies are not allowed to negotiate with those companies over the price of the drugs. When you go to buy a car, you’re a big buyer of a big-ticket item. You can negotiate over price. But the federal government is stuck. It can’t negotiate prices.

michael barbaro

And they’re a very big-ticket buyer.

donald g. mcneil jr.

Absolutely. That’s unusual and anti-business, and it’s only in the United States that that’s done, because the pharmaceutical lobby is so powerful.

michael barbaro

What else, conceivably, could the U.S. government do to bring down the costs of this drug?

donald g. mcneil jr.

Well, what the activists wanted to do is literally cancel the patent. There is provision under American law called march-in rights. This use for this drug was substantially paid for by the United States government. They paid for the trial that established PrEP. So if the drug is not available at a reasonable price, the government has march-in rights to go in, take the patent away from the company, and assign it to somebody else.

michael barbaro

Literally march in —

donald g. mcneil jr.

Yeah.

michael barbaro

— because of their financial stake?

donald g. mcneil jr.

It would be totally legal under American law to do that. The government has historically always hesitated to take away any sort of patent rights from the pharmaceutical industry.

donald g. mcneil jr.

Because they have a very powerful lobby.

michael barbaro

And there’s also perhaps the specter, which doesn’t feel entirely American in our capitalist system, of kind of nationalization, taking something from the private sector and kind of claiming it for the public sector.

donald g. mcneil jr.

Well, actually, the government does this kind of thing all the time. I mean, we have a concept of eminent domain. When you need to build a highway, you can take away somebody’s home. More importantly, this is actually a license that’s granted by the government. That’s what a patent is. So the government can take back a patent license the same way it can take away your driving license or your hunting license if you abuse it. And there is precedent for this. In the wake of the 9/11 attacks, the country was hit with anthrax. Supposedly there was only one cure for anthrax, and that was ciprofloxacin. Bayer, the same company that makes aspirin, held the patent on ciprofloxacin, and they were charging $13 a pill. The government wanted 200 million pills for its stockpile, and Bayer said, it’ll be $13. And the government said, no, that’s too much, and if you don’t lower the price, we can take away your patent on Cipro. And Bayer said, O.K., the price is $1.50. Bumpf, end of problem. And for public-health purposes, the activists argue the government should be doing it because the company is charging so much that people can’t get a vaccine-like medication that they need.

michael barbaro

So, Donald, what should we make of the fact that the government has not done any of the things that you just described to lower the price?

donald g. mcneil jr.

I think we should make it that the government doesn’t recognize how important it is to stop this disease, that you have to kind of pull out all the barriers in order stop H.I.V. And that means making it as easy to get on PrEP as it is to get a measles shot in this country. If you want to stop a disease, you have to protect everybody who’s at risk, and you need it to make it easy to protect them. Either the government has to go do it itself or make it really, really easy and cheap for people who are motivated enough to seek it out for themselves to go get it.

michael barbaro

Is what you’re really saying that the government doesn’t think AIDS is that big of a crisis?

donald g. mcneil jr.

AIDS has been around for more than 30 years now. And believe me, if this had been available back in the early days of the epidemic, this would have been the vaccine against H.I.V. Now that we’ve gone on for 30 years and it’s taken a long time to create these drugs and then realize that they could be used for prevention too, it’s like the government’s interest has waned. You don’t see people dying of H.I.V. anymore, so you don’t worry about it. And unfortunately, most of the people getting H.I.V. now are poor and black and living in the South, not gay and well-educated and living in New York City. So the political arm-twisting that goes on when you have a large, powerful lobby in New York City and Washington, D.C., just isn’t there anymore.

robert grant

I was thinking this morning that I wanted to tell you a story. This project went on over many years, and there were just so many people who gave so much to make PrEP research possible. And there’s one person I wanted to mention in particular, a sociologist that worked with me for 12 years. And he worked in my lab, and he guided the design of these studies. His name is Jeff McConnell. And in 2014, he died. He died shortly after the end of my research on PrEP. He was a man living with H.I.V. infection. And one of the questions I remember him asking was if we discovered a way to end the H.I.V. epidemic, would we? And I realize now that I don’t know the answer to that question. I feel like he’s still asking that question. If we found a way to end the H.I.V. epidemic, would we? And at the time, I was optimistic, and I was naive. I said, of course we would. Yeah, if we knew how to end it, we would end it. And right now, I have to say I’m not sure. I’m not sure we’d end it. Because I do know that we know how to end this epidemic. We have all the technology we need to end this epidemic, and yet we don’t. We don’t end this epidemic. And so I feel like I lied to Jeff. I told him yes, we would, and now I have to say I’m not sure. I’m not sure we would end the epidemic even once we know how to do it, because we do know how to do it, and we’re not doing it.

michael barbaro

We’ll be right back. Here’s what else you need to know today. During a news conference in London on Tuesday with Prime Minister Theresa May, President Trump said he believed that Brexit would eventually happen, despite May’s repeated failure to negotiate a deal.

archived recording (donald trump)

I would say, yeah, I would think that it will happen, and it probably should happen. This is a great, great country, and it wants its own identity. It wants to have its own borders. It wants to run its own affairs.

michael barbaro

The president said it was in the best interest of Britain to leave the European Union and promised that the U.S. would negotiate a, quote, “phenomenal trade deal with Britain” to ease its transition out of the E.U. And —

archived recording (ralph northam)

It is right to respond to this tragedy with decisive action. Let Virginia set an example for the nation that we can respond to tragedy with action.

michael barbaro

On Tuesday, in response to the mass shooting in Virginia Beach, Virginia’s governor, Ralph Northam, called for a special session of the state legislature to vote on a series of gun-control measures.

archived recording (ralph northam)

I will propose many of the same ideas that we have proposed before — universal background checks, a ban on assault weapons to include suppressors and bump stocks.

michael barbaro

Many of the measures proposed by Northam have already been voted down by Virginia lawmakers, and they face an uncertain fate in the Republican-controlled legislature. After Northam spoke, the speaker of the Virginia House of Delegates, Kirk Cox, called Northam’s request for a special session, quote, “hasty and suspect.” That’s it for “The Daily.” I’m Michael Barbaro. See you tomorrow.


Bron:
https://www.nytimes.com/2019/06/05/podcasts/the-daily/hiv-aids-truvada-prep.html

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