North Carolina Product Liability Lawyer Blog
Today, we’re going to talk about the HIV medication, Tenofovir. This was a medication sold for years to delay the progression of HIV. As studies are beginning to show, there were problems with the medication causing toxicity to kidneys, bone loss and bone injury. Whitney Butcher is an attorney with Hilliard Martinez and Gonzales, and today we’re going to talk about Tenofovir, the brand name medications that derive from this compound, the problems that were discovered and the litigation that has inevitably followed all this.
Let’s start at the beginning. Most people know that HIV is the virus that causes AIDS, what is an antiretroviral drug?
Whitney Butcher: So, those were one of the first class of drugs that were basically brought to market to help stop and slow the spread of HIV. Once a person contracts HIV, the goal of these medications is to target the cells and prevent them from replicating so that an HIV diagnosis doesn’t progress into full-blown AIDS which can of course be life-threatening and very dangerous.
Clay: What is Tenofovir?
Whitney: Tenofovir is a compound that’s in a class of nucleotides, and it’s very effective at preventing the replication of HIV, but it can be nephrotoxic meaning that it can harm patients’ kidneys. Tenofovir is the active compound that’s in a number of different antiretroviral medications. Truvada is one that a lot of folks have heard of.
Clay: In reading about this medication, when they were formulating it, around 20 years ago, it was only meant to be administered in an intravenous form, and the company, Gilead Sciences, was trying to make it into a pill form. Can you talk a little bit about that and kind of the downside and upside of that?
Whitney: So while Tenofovir is effective, it can’t be taken orally, which, as you just said Clay, means that you can’t put it by itself in a pill and have somebody take it. It just doesn’t work that way. So, what happens is, these delivery agents are added to the compound Tenofovir. The first drug involving Tenofovir was the class of medications that I’ll call TDF, that’s Tenofovir Disoproxil Fumarate, or TDF. The very first TDF medication that came on the market was called Viread, and that was approved in 2001. So, TDF is Tenofovir, the drug that will prevent the cells or slow the cells replicating the virus, and then the DF, the Disoproxil Fumarate, that’s the delivery agent. That’s what allows the patient to take Tenofovir orally in pill form and then allows the medication to get to the cells to do the work that it’s supposed to. So I kind of make a joke that the Tenofovir is the Amazon package that you’ve ordered, and the DF is the Amazon Delivery Agent, that’s going to deliver it to your front door. So, you’re not going to get the package unless you’ve got the DF. Tenofovir is not getting into cells without the delivery agent, the DF, that accompanies it.
Clay: Let’s move from talking about Tenofovir and going to TDF. What are some of the brand names that were out there under that TDF umbrella.
Whitney: Absolutely. The first one was Viread. That was approved in 2001. The next name brand TDF drug and, perhaps the biggest, was Truvada, and that was approved in 2004 by the FDA. And so, Truvada features TDF plus another component. So, with Viread, even though it was effective, patients would have to take lots of other medications. In the early days, HIV patients would talk about having to take like 10 different pills per day. So Truvada was the first to combine TDF plus an additional medication. The other interesting thing about Truvada is it was actually the first medication that was approved for PrEP, so what that means is for patients who might be at a higher risk of contracting HIV but are currently negative. The FDA approved Truvada to be used by those, overall, very healthy people as a preventative measure. Some other TDF medications, Atripla was a big one. Atripla, as the name suggests, kind of speaks to triple. So there’s three different compounds that make up Atripla. Another one, Complera, and then the last in the TDF class was Stribild, which had four different components to it, again, including TDF. And Stribild came out in 2012.
Clay: TDF is considered toxic to kidneys. Is that correct?
Whitney: Yes. As we’ve gotten more information and as we’ve had a chance to talk to patients who took TDF oftentimes years and years, what we’ve learned is that…so the TDF drugs, again, the Tenofovir is trying to get into the cells to prevent the replication. It’s less stable of a compound. And so, what happens is the changeover. So you take it as an oral pro-drug, right? Your body starts converting it into Tenofovir before it reaches the target cells, meaning that you get a greater systemic exposure. So, Tenofovir, at its core, is nephrotoxic, meaning that it can harm your kidneys. It can do positive things, but it can also harm your kidneys. And so by allowing for this greater systemic exposure, what we’ve seen is that TDF medications do have a higher likelihood of causing problems with people’s kidneys. And in the worst cases causing end-stage kidney failure that requires them to be on dialysis, which is really an awful thing for anyone to go through.
Clay: It’s just a shame because these are individuals, these are patients with a terrible illness in a lot of cases. It’s an awful choice they have to make. Obviously, they didn’t know for years that this medication was potentially that harmful, and yet, when they’re facing the prospect of AIDS, the development of AIDS, it’s horrendous choice they have to make. In my reading, it seems like the company that developed TDF knew even prior to 2001, when the first class of these drugs came out, that TDF was toxic to the kidneys and quite potentially harmful to the human body. Isn’t that correct?
Whitney: That’s certainly what we believe. We’re still in the early stages of discovery. So we’re working through a lot of that. But yes, Tenofovir was nephrotoxic. Everybody knew it was nephrotoxic. We believe that the company knew that TDF had a greater likelihood to cause kidney damage in patients before it was approved.
Clay: An excellent point you’re making. And let’s stop for a second and say we’re both attorneys, and some of the things we’re talking about today are allegations made in complaints against the company. And the job of the plaintiffs is to go out there and prove it, so Gilead is going to certainly deny a lot of the allegations that we talked about today. Speaking of allegations and things we’ve discovered, along the way, at some point, Gilead came up or developed a safer alternative to TDF. Isn’t that true?
Whitney: So this is important. I don’t mean to sound like I’m correcting you because you’re the boss Clay, but it wasn’t at some point down the line. It was initially, I mean, we believe that they had these two drugs in the hopper at about the same time. So TDF and then its safer alternative, TAF, were kind of in existence at the same time. And Gilead, we believe, made the choice to shelve TAF, which ultimately proved to be a safer alternative, meaning it was as effective, if not more so, at preventing the spread of HIV, but it didn’t have the side effects of kidney failure and then ultimately bone mineral density issues and other fractures that we saw with the TDF drug. So it wasn’t that they got TDF on the market and they stumble on TAF at some time later. We believe that it was there to be seen and developed instead of TDF from the beginning.
Clay: I appreciate that distinction. And that actually gets to the heart of this thing and makes it a little more sinister if the plaintiffs are able to prove that it’s true. Tell me how TAF is noticeably safer than the TDF.
Whitney: So again, the active drug in TDF or in TAF is Tenofovir. And so, TAF stands for Tenofovir Alafenamide Fumarate. So the AF are the delivery agents and they’re more stable. What that means is when you take the oral medication, that is TAF, it stays in that encapsulated form longer and doesn’t begin the conversion process to Tenofovir until it actually reaches the target cells. So, it’s not causing all this systemic exposure because the switch over to TAF or Tenofovir isn’t happening while it’s in the body. It’s more stable. It’s a more stable compound, and so, it maintains its integrity until it gets in the target cells and then switches over to Tenofovir, which makes it more effective, we believe. But then also, it’s not causing the systemic exposure and being processed through the patient’s kidneys which can then cause a lot of the kidney issues that we’ve seen with folks who took Truvada and other TDF medications.
Clay: So to say it back to you: with both medications, TDF and TAF, their usefulness is because of the Tenofovir that’s present and it’s effective in slowing down HIV progression. But that said, the study shows that TAF is markedly safer than the TDF. Now, Gilead had both around the same time, we believe, chose to keep selling the TDF branded medications. Do you have a theory why?
Whitney: The theory would be to maximize profits. I hate to say it as bluntly as that, but with both on the market, you’re competing for the same population of patients. So, if you have one, that’s the only option on the market. You can extend the patent life of the drugs. Everybody’s heard of generic medications, right? So there’s a period of time, seven or ten years, when a drug gets approved. It’s the only game in town, if you will. And so, we believe, to maximize profits, Gilead wanted TDF drugs to be the only game in town, the only option with Tenofovir for prescribers so as to maximize their profits. Then, when they were approaching the end of patent life of the TDF medications, they would roll out the TAF drugs because they wouldn’t have the protection from generic competitors for TDF, so let’s try to switch everybody over to TAF because those are newly approved, we’re the only game in town now with the TAF drugs.
Clay: The implications are horrifying, if this is true, that for twelve, fifteen years, Gilead was making sure that TDF was front and center, and then they slow-waltzed the TAF medications which they knew to be safer. And again, some of these are allegations that must be proven. But I did read that the TDF drugs were the major part of the sales figures for Gilead in the early part of the 2000s, like as much as 68% of all Gilead sales in 2003. Is that your understanding?
Whitney: I’m not familiar with that number, but I have no reason to doubt it; it sounds right.
Clay: I talk a lot on my site about the profit motive that drives a lot of these corporations. We all know every corporation has a profit motive, but the extent to which the profit motive can drive devastating decisions for public health is just [horrifying]. I stumble on a new example of it every week it seems. So, in 2015, the TDF drugs were getting closer to the expiration of the patent, and Gilead started to move toward TAF medications. Is that right?
Whitney: Yes.
In Part 2, Clay and Whitney discuss the injuries that Tenofovir can cause, and the emerging litigation against Gilead.