March 13, 2025 • 27 mins
Jared Baeten is senior vice president in virology at Gilead Sciences. Jared's problem is this: In a world without a vaccine, how do you make a medicine that people will actually take to help prevent HIV?
There’s already a daily pill that reduces the risk of getting HIV, but a majority of people who are at high risk are unwilling or unable to take it.
So Jared and his colleagues are developing a new drug, lenacapivir, designed to be given as a shot once every six months.
Note: The views and opinions expressed in this episode are those of the guest and do not necessarily reflect the views or positions of any entities they represent.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:15):
Pushkin. So I'm curious in your own life when you
first became aware of HIV and AIDS.
Speaker 2 (00:29):
Oh gosh, this is a great question to start interview.
I am fifty I did one, so I do remember.
I remember the first news stories as a you know,
as a child. It's also been a driver of everything
I've worked on and wanted to work on.
Speaker 1 (00:51):
I am also fifty one, coincidentally, and I you know,
I vaguely remember the world before HIV and AIDS. I
also remember, and I'm sure you remember this too, like
coming of age at a time when if you got AIDS,
you died, and you could get it from having sex.
Speaker 2 (01:09):
Uh.
Speaker 1 (01:10):
To me, that's the that's the big imprint it left
on my own you know, narrowly, narcissistically on my own life.
Speaker 2 (01:17):
Yes, so much fear, right, so much, so much death,
so much destruction, destruction of potential, and so much fear
and surgainly for a generation to have fear and sex
so coupled with each other, so intertwined. But it's always
(01:38):
driven me to to to end HIV is to be
able for you know, there to be a generation who
didn't have that cloud of fear in their lives.
Speaker 1 (01:54):
I'm Jacob Goldstein and this is What's Your Problem, the
show where I talk to people who are trying to
make technological progress. My guest today is Jared Bayton. He's
senior vice president in virology Achillead Sciences. Jared's problem is this,
in a world without a vaccine, how do you prevent
people from getting HIV. It's been clear for years that
(02:17):
taking a daily pill dramatically reduces the risk of getting HIV,
but as you'll hear, the vast majority of people who
are at high risk for getting HIV just don't take
a pill every day. Now, Jared and his colleagues are
working on a new option, a drug called leni kapavir
that you get as a shot once every six months.
(02:39):
The drug has not yet been approved to prevent HIV,
but there have been some really compelling results from a
couple big clinical trials. There's a lot that's interesting in
the show today, how medicine only works if it meets
people where they are, and how what seemed like a
big problem for Lena kapavir may turn out to be
the key to its success. But we started with Jared's
(03:00):
own career, which tracks a lot of the history of
HIV and AIDS and the emergence of drugs that can
prevent people from becoming infected. So when do you decide
to make fighting HIV your career.
Speaker 2 (03:17):
When I went to graduate school and medical school, I
was when I decided to work on HIV that I
wanted to do health work that was meaningful to the world.
That was that it was and it was immediately actionable.
As a graduate student during medical school, I lived and
worked on HIV prevention in Kenya. Obviously before there was
(03:39):
medicine for prevention, and I remember very well, even before
there was very good testing. I was a strain of
thought at the time that testing was too scary to
do because there was nothing to be done.
Speaker 1 (03:52):
Wow.
Speaker 2 (03:53):
I certainly had other doctors say that to me. I
the hospital that I worked in Kenya, the only testing
that was done was so people could stop spending money
on their family members.
Speaker 1 (04:05):
Oh my god, So meaning, oh, don't spend any money
on them. They have HIV, They're going to die. That's
why they were doing the tests.
Speaker 2 (04:13):
Yeah, someone in the hospital extraordinarily sick. Let's do an
HIV test. Okay, you can stop spending money. Jesus and
then really importantly, I remember when medicines came. I remember
when medicines came. I remember when I remember very well
when the coffin makers who would work in the street
outside the hospital start going out of.
Speaker 3 (04:30):
Business, the coffin makers, the coffin makers, yep, holy yahkah,
which gosh, the Kenya's prevalence maybe at fifteen percent or
something like that at some point, and it's.
Speaker 2 (04:44):
Not much lower to be able to see in that
country and other countries what medicines can do. And that's
actually that's what drove a lot of signs. I've always done,
is HIV prevention and then HIV treatment, but making medicines
that make a difference in people's lives, and like what
good medicines did for HIV care here in the US
(05:06):
where I live from, in many parts of Africa where
I've worked, and how fundamentally transformed, how socially transformative, how
something risked really destroying in fraction societies, and how good
science was able to arrest that in averse.
Speaker 1 (05:23):
Then so okay, so that's what's happening, you know, around
the turn of this century. And then there's this new
idea that comes along after that right, and that is
what if we can use these drugs to prevent people
at high risk from getting HIV in the first place. Right,
This idea called prep Where does that come from?
Speaker 2 (05:46):
So this idea of prep pre exposure, prople axis, you
take a medicine. By having that medicine, your bloodstreams, your
tissues or whatever, you if you expose to the virus,
it doesn't take hold. Yeah, and the idea of propyle
axis is not totally novel in infectious diseases. If you've
ever traveled to a place with malaria, you've probably taken
(06:07):
a malaria propyle axis that kind of idea, But they
do prep for HIV was super surprising at the time.
Speaker 1 (06:15):
Huh.
Speaker 2 (06:15):
You have to have a medicine that would work to
prevent HIV and HIV is very transmissible, so to avert
infection would be a high bar. And then it has
to be medicine itself that's very well tolerated, very safe
because you're it would be given to healthy individuals who
don't have affection, and the societal medical tolerance for side
(06:38):
effects for treating HIV, just like treating any really serious
dead latencies, is different than but for preventing.
Speaker 1 (06:44):
It, sure, it has to be lower risk. Right, if
you already have HIV and you're going to die, you're
willing to take a right medicine that has pretty severe
side effects, whereas if you're healthy, you're not going to
take some really harsh, risky drug just in case.
Speaker 2 (06:59):
Exactly exactly right and unfortunately for treating HIV. Just for
your listeners, like the complexity and the side effects of
the medicines from the late nineties and two thousand have
changed dramatically in the last couple of decades, and so
that most people these days actually take a single pill
once a day, extremely well tolerated, and live what's expected
(07:21):
to be a full lifespan lived as long as someone
who doesn't have HIV and are on infections. So just
so people know what's changing. But in early two thousands,
medicine still had side effects.
Speaker 1 (07:31):
Were you working on PREP at this time?
Speaker 2 (07:33):
I worked on one of the two trials that formed
the registrational package of PREP, one in mostly gave men
and some transgender individuals, and then one in heterosexual individuals,
women and men, And that was the second one was
the study that I worked on with collaborators from all
over the world. And based in Kenyan. You gotta it
(07:54):
was almost five thousand couples where one person didn't have
HIV and the other one did.
Speaker 1 (08:01):
So that's a very high risk setting, very.
Speaker 2 (08:03):
Higher setting, and also setting where there was tremendous motivation
to have a different life experien for the couple it was.
It was a really remarkable time because there was lots
of questions where the park would work at all. There
was not a question where it could be safe enough
and go to the trials demonstrated both safety and HIV protection.
Protection that was dependent on people taking it. Like all medicines,
(08:26):
medicines only work if you take them, and there are
all kinds of different motivations to take something, predict something
that's every day, and some people really succeed and some
people really struggle. As you can access.
Speaker 1 (08:36):
So you are, they're setting up the next turn in
our story, which is the new drug we are here
to talk about, right, But let's just do that for
a minute more, because as you said that the drugs
people can take to prevent getting HIV have gotten easier
(08:56):
to take and better tolerated. And you know, if you
can take one pill a day and you're in a
high risk setting and that means you have a profoundly
lower risk of getting HIV. Like, what's the problem? Like
I feel like, great work, thank you for doing that
good work, and like it seems like you're there.
Speaker 2 (09:18):
I'm sure there were moments where I thought, it seems
like we're there. This seems obvious to me as well. Yeah,
I remember well the first day. Its actually years after
the first medication for PREP was approved, where it had
never been something like this hadn't been rolled out in clinics,
so like people doctors didn't have the conversation pieces to
(09:41):
talk with this, patients or individuals who wanted PREP didn't
always have heard about it or didn't have the practice
and asking for it. And it was slow. It was
slow going, slow going in this country, slow going around the.
Speaker 1 (09:55):
World, slow going meaning people just didn't take it that much.
Healthy people didn't want to take a pill every day.
Speaker 2 (10:02):
Yeah, I was like, yes, this is hard, like new
innovations and health are hard because none of us make
health decisions, or at least I think most of us.
Most of us do not make health decisions just because
someone tells us to or because the science is really excellent.
We make health decisions because we think it's going to
be meaningful for us. So whether that's like what we
eat or going to gym, or like what we buy
(10:24):
off Instagram or whatever else for our health, Like, we
make those decisions because we think it's meaningful for us.
And something like PREP, which can be extorted and meaningful,
it has to be extortedly meaningful for someone to want
to make the effort to go to get it and
to continue it. There are many many people who take
PREP every single day. It fits into their lives. It
(10:44):
brings benefit, and it brings meeting and they can make
it workable within their lives. And then there have been
many people who have tried and stopped or not tried
at all. And that's like setting up for my rest
for our discussion. Just because you have something that works
for some people, that airing that bottle home or it
(11:08):
could be found by an aunt, partner or brother or
whatever is too much, too much disclosure, too much revealing.
Speaker 1 (11:20):
It means you're having sex, probably right, yeah.
Speaker 2 (11:23):
Exactly, Or the complexity of the of taking something every
day when you've got two jobs and three kids or
whatever the things are that for something that you don't
really want to think about every day.
Speaker 1 (11:36):
Yeah, it's a very good qualitative description. Is there a
quantitative piece like, have you estimated the population that you
know might be relevant but doesn't want to take a
pill every day in the first place.
Speaker 2 (11:48):
Yeah, In the US, CC is estimated that maybe about
a third of the people who would most benefit from
taking PREP, not even like benefit at all, but like
most benefit from taking PREP are taking it sort of
today we are taking it day to day.
Speaker 1 (12:02):
Wait, one third of the people who are at highest
risk for getting HIV are taking it. So two thirds
of the people are.
Speaker 2 (12:09):
Not exactly so, a third r a third arth, two
thirds are not.
Speaker 1 (12:13):
So okay, So there is this idea that PREP is great,
but most people who could most benefit from it don't
take it. One thought as well, if instead of having
to take a pill every day, it was less frequent,
simple behavioral thing, maybe people would do it more often.
And so so there's this search for a for a
(12:35):
new drug that is longer lasting, right, that you in
fact have found spoiler alert, But tell me about the
search for that drug.
Speaker 2 (12:42):
The idea was that HIV has a structural element called
it's capsid, where it encloses the nucleic acid of the
virus within the virus.
Speaker 1 (12:52):
It's it's like it's the bag, right, It's the protein.
Speaker 2 (12:54):
It's yeah, it's a protein coming. It's like a yeah.
And I always want to think it's stronger than the bag.
It's stronger than a bag.
Speaker 1 (13:02):
It's like okay, it like akayas case flask okay, okay.
Speaker 2 (13:07):
And that's the virus is coming into the cell that
opens and dumps the new class ass and out. So
the virus is infecting and when it leaves it encapsulates
the begin and floats away. And targeting that is particularly hard,
and the work on it began a dozen years before
took a dozen years from the work to start before
we've even tested any human being for the first time,
(13:28):
and four thousand molecules were synthesized and screened in test
tubes and animals, selling them other things to be able
to be able to bring forward one to be able
to test in human beings, which then became a lot
of capeer.
Speaker 1 (13:45):
We'll be back in a minute.
Speaker 2 (13:56):
A virus like HIV has a certain number of proteins
that make it function right and caps it had not
been targeted and as a result of a great question
to say, could we target this part of the virus
in a way that it's different. This is important for
HIV broadly because what has been the success of treating
HIV is being able to target the virus in multiple places,
(14:20):
in multiple components of its life cycle, and that is
what makes up a treatment cocktail for HIV. Multiple medications
usually the target different parts of the virus life cycle
at the same time, and from a safety point of view,
actually ones that are very specific to the virus itself
and don't have effects on us. And so a enzyme
(14:43):
that only the virus makes, or in this case, protein
protein interaction that only the virus has, is a great
target because there's nothing that looks like that in our
regular systems.
Speaker 1 (14:56):
So basically that means people are likely to have fewer
side effects because our own cells aren't gonna be bothered.
So it seems like a promising target because it's this
weird thing that the virus does that we don't do.
And then drug researchers find this, this molecule, right, this
potential drug that will eventually be called len.
Speaker 2 (15:14):
A cap of bear.
Speaker 1 (15:15):
But but there's what seems like a problem with this
with this molecule, right, and the problem is that it's
not very soluble in water. It doesn't dissolve well in water.
Tell tell me about that part of it.
Speaker 2 (15:28):
There people who work on it. Just sometimes you do
a lot of work to try to figure out the
best what's got the best attack on the virus itself
around the end time you're trying to target itself. And
then it's not particularly soluble problem because that like medicines
that we take through our mouth, for example, like most
medicine surge IVY need to dissolve an order for us
(15:49):
to absorb them. And actually a lot of work goes
into one one's doing drug development, and maybe you figure
out the thing that targets best, and then you figure
out how to modify it ever as best you can
to be able to absorb it, because if you can't
absorb it doesn't have an effect.
Speaker 1 (16:02):
Right you want you want it to dissolve in water.
You want to take it and then it dissolves and
goes off into your correct exactly.
Speaker 2 (16:11):
It's the tremendous advantage of Lena kaeper beer has been
for what it eventually became is that when it's formulated
as an injection, it forms a deepot of the drug,
well deposit of the drug that dissolves slowly over time
because it isn't immediately soluble.
Speaker 1 (16:31):
And like, was there a moment when somebody sort of
just realized like, oh, this this bug could actually be
you know, like an amazing feature. You know the fact
that it's not soluble, like it might mean we could
give this drug to people and it would last a
really long time.
Speaker 2 (16:46):
I don't think that there's an exact moment. I think
there's actually many moments along the way or a discovery
like this, it's what do we have? How do we
improve on that? Where could we get to? And I
think the I will tell you the very first testing
of lena caprier was not a six month injection.
Speaker 1 (17:02):
So over time, a lot of whiteboards, a lot of
rooms full of people, you get to this idea of oh,
we could do this as an injection that lasts four
months and months.
Speaker 3 (17:11):
Right.
Speaker 2 (17:11):
Yeah.
Speaker 1 (17:12):
So there's two big sort of pivotal trials that you run, right,
tell me about them.
Speaker 2 (17:17):
It's actually an entire program called Purpose And there are
two trials, Purpose one in Purpose two.
Speaker 1 (17:23):
What's the acronym you say, Purpose? I got to ask
you for the acronym.
Speaker 2 (17:26):
Oh, no, so the actually that acronym really is really complicated.
It is not a clear pee you are, so, yeah, no, yeah,
I don't make these up. But the trials are run
across five continents, thousands of people, almost ten thousand people
in total. And the two trials Purpose one and two
(17:48):
were the trials that specifically are phase three pivotal trials
for testing whether something is safe and effective.
Speaker 1 (17:56):
And what were the results?
Speaker 2 (17:58):
Yeah, so Purpose one is among Allison girls and young
women in South Africa Uganda. It's almost five thousand people
in the trial who were either taking the daily pill
or taking the injection. And the among people who were
assigned the injection, zero infections occurred for the primary d
priant of the trial, which had never been seen before
(18:19):
for an HIV prevention trial.
Speaker 1 (18:21):
So okay, so zero absolutely no. One of the two
thousand or so people who got lenni kapavir, none of
them got HIV in the control group. So they were
taking in the control group of the anti retroviral pills
that are standard. Now, how many of those people got HIV.
Speaker 2 (18:40):
For people who are getting the control pill, which is
active prep, the approved active crap, sixteen out of about
one thousand.
Speaker 1 (18:51):
So sixteen out of a thousand is kind of a lot.
This is like over the course of what a year.
Speaker 2 (18:54):
Or something about a year a year follow and in
almost all the cases of the sixteen it's because invested
blood samples from those individuals they weren't using it, and
a testament to for some people how challenging it can
be to use something every day and how something that
(19:15):
injection twice a year for many people both could be
very effective, but also is something that they can make
workable because you can set it and not think about.
Speaker 1 (19:26):
It, Okay, forget it. What's the other What was the
result of the second pivotal trial.
Speaker 2 (19:34):
Yeah, the second pivotal trial was the more geographically diverse
group and was men, transgender women, and men and gender
non binary people in Asia, North and South America and Africa.
It's really broad and global. Yes, And in that study,
again among about two thousand people, there were only two
infections that occurred compared to nine infections among about a
(19:58):
thousand people who received the control so also quite a difference.
Speaker 1 (20:03):
Yes, I mean, presumably the larger audience or the larger
patient population is the people who aren't taking oral prep
at all. Precisely, and you can't randomize ethically to that.
You can't have a control group where it's like we're
not going to give them anything and we're going to
see how they do. But in real life, that is
probably the population you're looking for.
Speaker 2 (20:21):
Right exactly.
Speaker 1 (20:22):
So okay, congratulations on the successful outcome of the trials.
Where are you now?
Speaker 2 (20:29):
Oh so you know, bigger mind we talked about before.
You know, just because science can be the science may
be fantastic, you may have a great publication or a
great p value for science, it doesn't mean that people
actually get medicine. And so the medicine when the cover
has been submitted to regulatory agencies, because drug approvals.
Speaker 4 (20:48):
Are a necessary step for people to receive them, and
that rigorous process is ongoing now and regulatory parentcies all
around the world.
Speaker 2 (20:58):
From the beginning, the thought has been for loutic cover
that's a medicine that can have a global impact, and
then readying for being able to make it and distribute
it for people all around the world. As we have
been doing all of those steps, the dissemination of the science,
the regulatory submissions, we've been simultaneously making plans for global
(21:21):
access particularly access for low and lower middle income countries,
and that part of the story is as important as
everything else because success for ending HIV is it has
to be a global success.
Speaker 1 (21:32):
Yeah, so let's talk about that. I mean, there's obviously
an interesting history of getting HIV drugs to lower income
countries that largely has been a success. Right, people don't
talk about it that much anymore, but it's a good,
happy story. Ultimately, what's happening with Lena kapavir that in
that context, Yes, the the.
Speaker 2 (21:55):
You know, we talked back about my earlier history and
I remember well when there were no medicines in lower
middle income countries and then when there was, and that
was a delay of years and years. And that's not
unique to HIV. That is for innovations and health in general,
that it can take years or decades for medicines to
make it from when they're discovered to even approval and
(22:19):
then availability in low income countries. For lenikapavier years ahead
of results, truly years ahead before we had results. We
were thinking about how we can compress that calendar, and
that included within weeks of the Purpose trials reading out
(22:40):
an announcement that we'd signed voluntary license agreements which are
which allow a generic manufacturer to make a version of
the medicine. So would volntarize de agreees with six generic
manufacturers covering one hundred and twenty countries low and lower
mediome countries to be able to make generic versions in
the medicines royalty free and no profit real that as
(23:02):
soon as they're able to, so as soon as they
can ramp up their technical capacity to be able to
make these medicines.
Speaker 1 (23:10):
So it will be cheap for people in four parts
of the world. And what does that mean sub Saharan Africa,
parts of Asia exactly? What about well, what's it going
to cost in the US? And how does how does
like insurance work for PREP? Insurance cover PREP.
Speaker 2 (23:25):
So insurance dots cover PREP in the United States. And
the CDC has done really extensive analysis yes, to summarize
a lot of really good signs there their conclusions that
access to PREP is not limited by insurance coverage, that
there are two thirds of people who could most benefit
using PREP. That's not for insurance reasons, that is for
(23:45):
all kinds of the other reasons that we talked about
of stigma and and I think that's a strategy looking
forward to to len ACAFA. It's not proved yet United States,
so there's not both insurance coverage and other things are
not said yet. Those don't happen until the FDA is
able to do their rigorous assessment about the efficating and
safety of the medicine.
Speaker 1 (24:04):
So, Okay, you've been working on HIV for for a
long time now, right for deaths, And I'm curious when
you sort of take the long view and you step back,
what do you see?
Speaker 2 (24:15):
Oh, you know, I have been doing this for a
long time, and what has always motivated me is you
know it is actually ending the epidemic.
Speaker 1 (24:25):
When you say ending the epidemic, I mean like I
think of a vaccine and a global eradication campaign. Is
that what you mean when you say that.
Speaker 2 (24:34):
I want to stop new infections. I want to be
able to stop my infections as much as we can.
I want to have treatments that are availed to every
person living with HIV that allow them to live a
full life, and as a result, turning off the tap
of new infections, treating effectively the infections that are existing,
then the public health emergency diminishes, and the cloud that
(24:59):
is ACHIV on the world.
Speaker 1 (25:04):
We'll be back in a minute with the lighting round.
You have undergraduate degrees, as I understand it, in both
biochemistry and comparative religion. Which religions did you compare in
which one.
Speaker 2 (25:24):
One one one?
Speaker 1 (25:28):
Which one lost?
Speaker 2 (25:30):
Now I have an undergraduator in comparative religion, which I love.
I love the interface of society and health, society and
person of religion. Degree was a great way to get out.
Speaker 1 (25:41):
I mean, tell me one thing, like what were you
actually interested in?
Speaker 2 (25:45):
What? What? Like?
Speaker 1 (25:45):
What like? Tell me one thing you learned in studying
comparative religion.
Speaker 2 (25:50):
Oh, I don't many things in comparive religion. I loved.
I love complicated religious texts on how societies have fought
through mystery in the world. I loved American religions because
there's so much variety in the United States and it
reflects a lot of the energy of the US for
you know, all different directions. I have dynamism of dynamism
(26:13):
of religion, and what religion says about society like still
influences my all of the stuff I do.
Speaker 1 (26:19):
Now, what's your second least favorite virus?
Speaker 2 (26:24):
Second least favorite virus?
Speaker 1 (26:26):
I'm assuming HIV is your least favorite.
Speaker 2 (26:29):
HIV is my well, HIV is my favorite book favorite.
Speaker 1 (26:32):
There's two ways to frame it, right, favorite or least favorite,
kind of the same. What's the number two after HIV?
Speaker 3 (26:38):
Oh?
Speaker 2 (26:39):
Hmm? Flu? Like which one is? I want to like
white from the world. Flu would be great, big impact,
terrible viruses that would be like a Goola Marburg that
we'd love to that I'd love to see remove the world.
All the viral epatitis viruses there's multiples of them that
(27:00):
have tremendous prevalence in the world and don't get as
much attention but kill lots of people. Would be great
to eradic it.
Speaker 1 (27:09):
How many papers have you co authored that quote, Tina Turner?
Speaker 2 (27:13):
Oh, the quote one, Yes, there's one. There's there's one
with a what's love got to do with the title? Yes?
Which is about it was about like the motivations to
take prep right, the motivations to take prep are not
simply because someone waged their finger at you and said
take your medicine. Yeah. Love.
Speaker 1 (27:36):
Jared Baton is senior vice president in virology at Kilead Sciences.
Just a quick note, we'll be off for the next
few weeks on a planned hiatus.
Speaker 2 (27:46):
We'll be back soon.
Speaker 1 (27:47):
Today's show was produced by Gabriel Hunter Chang, edited by
Lydia Jean Kott, and engineered by Sarah Buguer. I'm Jacob Goldstein.
Speaker 2 (27:55):
Thanks for listening.
Pushkin. So I'm curious in your own life when you
first became aware of HIV and AIDS.
Speaker 2 (00:29):
Oh gosh, this is a great question to start interview.
I am fifty I did one, so I do remember.
I remember the first news stories as a you know,
as a child. It's also been a driver of everything
I've worked on and wanted to work on.
Speaker 1 (00:51):
I am also fifty one, coincidentally, and I you know,
I vaguely remember the world before HIV and AIDS. I
also remember, and I'm sure you remember this too, like
coming of age at a time when if you got AIDS,
you died, and you could get it from having sex.
Speaker 2 (01:09):
Uh.
Speaker 1 (01:10):
To me, that's the that's the big imprint it left
on my own you know, narrowly, narcissistically on my own life.
Speaker 2 (01:17):
Yes, so much fear, right, so much, so much death,
so much destruction, destruction of potential, and so much fear
and surgainly for a generation to have fear and sex
so coupled with each other, so intertwined. But it's always
(01:38):
driven me to to to end HIV is to be
able for you know, there to be a generation who
didn't have that cloud of fear in their lives.
Speaker 1 (01:54):
I'm Jacob Goldstein and this is What's Your Problem, the
show where I talk to people who are trying to
make technological progress. My guest today is Jared Bayton. He's
senior vice president in virology Achillead Sciences. Jared's problem is this,
in a world without a vaccine, how do you prevent
people from getting HIV. It's been clear for years that
(02:17):
taking a daily pill dramatically reduces the risk of getting HIV,
but as you'll hear, the vast majority of people who
are at high risk for getting HIV just don't take
a pill every day. Now, Jared and his colleagues are
working on a new option, a drug called leni kapavir
that you get as a shot once every six months.
(02:39):
The drug has not yet been approved to prevent HIV,
but there have been some really compelling results from a
couple big clinical trials. There's a lot that's interesting in
the show today, how medicine only works if it meets
people where they are, and how what seemed like a
big problem for Lena kapavir may turn out to be
the key to its success. But we started with Jared's
(03:00):
own career, which tracks a lot of the history of
HIV and AIDS and the emergence of drugs that can
prevent people from becoming infected. So when do you decide
to make fighting HIV your career.
Speaker 2 (03:17):
When I went to graduate school and medical school, I
was when I decided to work on HIV that I
wanted to do health work that was meaningful to the world.
That was that it was and it was immediately actionable.
As a graduate student during medical school, I lived and
worked on HIV prevention in Kenya. Obviously before there was
(03:39):
medicine for prevention, and I remember very well, even before
there was very good testing. I was a strain of
thought at the time that testing was too scary to
do because there was nothing to be done.
Speaker 1 (03:52):
Wow.
Speaker 2 (03:53):
I certainly had other doctors say that to me. I
the hospital that I worked in Kenya, the only testing
that was done was so people could stop spending money
on their family members.
Speaker 1 (04:05):
Oh my god, So meaning, oh, don't spend any money
on them. They have HIV, They're going to die. That's
why they were doing the tests.
Speaker 2 (04:13):
Yeah, someone in the hospital extraordinarily sick. Let's do an
HIV test. Okay, you can stop spending money. Jesus and
then really importantly, I remember when medicines came. I remember
when medicines came. I remember when I remember very well
when the coffin makers who would work in the street
outside the hospital start going out of.
Speaker 3 (04:30):
Business, the coffin makers, the coffin makers, yep, holy yahkah,
which gosh, the Kenya's prevalence maybe at fifteen percent or
something like that at some point, and it's.
Speaker 2 (04:44):
Not much lower to be able to see in that
country and other countries what medicines can do. And that's
actually that's what drove a lot of signs. I've always done,
is HIV prevention and then HIV treatment, but making medicines
that make a difference in people's lives, and like what
good medicines did for HIV care here in the US
(05:06):
where I live from, in many parts of Africa where
I've worked, and how fundamentally transformed, how socially transformative, how
something risked really destroying in fraction societies, and how good
science was able to arrest that in averse.
Speaker 1 (05:23):
Then so okay, so that's what's happening, you know, around
the turn of this century. And then there's this new
idea that comes along after that right, and that is
what if we can use these drugs to prevent people
at high risk from getting HIV in the first place. Right,
This idea called prep Where does that come from?
Speaker 2 (05:46):
So this idea of prep pre exposure, prople axis, you
take a medicine. By having that medicine, your bloodstreams, your
tissues or whatever, you if you expose to the virus,
it doesn't take hold. Yeah, and the idea of propyle
axis is not totally novel in infectious diseases. If you've
ever traveled to a place with malaria, you've probably taken
(06:07):
a malaria propyle axis that kind of idea, But they
do prep for HIV was super surprising at the time.
Speaker 1 (06:15):
Huh.
Speaker 2 (06:15):
You have to have a medicine that would work to
prevent HIV and HIV is very transmissible, so to avert
infection would be a high bar. And then it has
to be medicine itself that's very well tolerated, very safe
because you're it would be given to healthy individuals who
don't have affection, and the societal medical tolerance for side
(06:38):
effects for treating HIV, just like treating any really serious
dead latencies, is different than but for preventing.
Speaker 1 (06:44):
It, sure, it has to be lower risk. Right, if
you already have HIV and you're going to die, you're
willing to take a right medicine that has pretty severe
side effects, whereas if you're healthy, you're not going to
take some really harsh, risky drug just in case.
Speaker 2 (06:59):
Exactly exactly right and unfortunately for treating HIV. Just for
your listeners, like the complexity and the side effects of
the medicines from the late nineties and two thousand have
changed dramatically in the last couple of decades, and so
that most people these days actually take a single pill
once a day, extremely well tolerated, and live what's expected
(07:21):
to be a full lifespan lived as long as someone
who doesn't have HIV and are on infections. So just
so people know what's changing. But in early two thousands,
medicine still had side effects.
Speaker 1 (07:31):
Were you working on PREP at this time?
Speaker 2 (07:33):
I worked on one of the two trials that formed
the registrational package of PREP, one in mostly gave men
and some transgender individuals, and then one in heterosexual individuals,
women and men, And that was the second one was
the study that I worked on with collaborators from all
over the world. And based in Kenyan. You gotta it
(07:54):
was almost five thousand couples where one person didn't have
HIV and the other one did.
Speaker 1 (08:01):
So that's a very high risk setting, very.
Speaker 2 (08:03):
Higher setting, and also setting where there was tremendous motivation
to have a different life experien for the couple it was.
It was a really remarkable time because there was lots
of questions where the park would work at all. There
was not a question where it could be safe enough
and go to the trials demonstrated both safety and HIV protection.
Protection that was dependent on people taking it. Like all medicines,
(08:26):
medicines only work if you take them, and there are
all kinds of different motivations to take something, predict something
that's every day, and some people really succeed and some
people really struggle. As you can access.
Speaker 1 (08:36):
So you are, they're setting up the next turn in
our story, which is the new drug we are here
to talk about, right, But let's just do that for
a minute more, because as you said that the drugs
people can take to prevent getting HIV have gotten easier
(08:56):
to take and better tolerated. And you know, if you
can take one pill a day and you're in a
high risk setting and that means you have a profoundly
lower risk of getting HIV. Like, what's the problem? Like
I feel like, great work, thank you for doing that
good work, and like it seems like you're there.
Speaker 2 (09:18):
I'm sure there were moments where I thought, it seems
like we're there. This seems obvious to me as well. Yeah,
I remember well the first day. Its actually years after
the first medication for PREP was approved, where it had
never been something like this hadn't been rolled out in clinics,
so like people doctors didn't have the conversation pieces to
(09:41):
talk with this, patients or individuals who wanted PREP didn't
always have heard about it or didn't have the practice
and asking for it. And it was slow. It was
slow going, slow going in this country, slow going around the.
Speaker 1 (09:55):
World, slow going meaning people just didn't take it that much.
Healthy people didn't want to take a pill every day.
Speaker 2 (10:02):
Yeah, I was like, yes, this is hard, like new
innovations and health are hard because none of us make
health decisions, or at least I think most of us.
Most of us do not make health decisions just because
someone tells us to or because the science is really excellent.
We make health decisions because we think it's going to
be meaningful for us. So whether that's like what we
eat or going to gym, or like what we buy
(10:24):
off Instagram or whatever else for our health, Like, we
make those decisions because we think it's meaningful for us.
And something like PREP, which can be extorted and meaningful,
it has to be extortedly meaningful for someone to want
to make the effort to go to get it and
to continue it. There are many many people who take
PREP every single day. It fits into their lives. It
(10:44):
brings benefit, and it brings meeting and they can make
it workable within their lives. And then there have been
many people who have tried and stopped or not tried
at all. And that's like setting up for my rest
for our discussion. Just because you have something that works
for some people, that airing that bottle home or it
(11:08):
could be found by an aunt, partner or brother or
whatever is too much, too much disclosure, too much revealing.
Speaker 1 (11:20):
It means you're having sex, probably right, yeah.
Speaker 2 (11:23):
Exactly, Or the complexity of the of taking something every
day when you've got two jobs and three kids or
whatever the things are that for something that you don't
really want to think about every day.
Speaker 1 (11:36):
Yeah, it's a very good qualitative description. Is there a
quantitative piece like, have you estimated the population that you
know might be relevant but doesn't want to take a
pill every day in the first place.
Speaker 2 (11:48):
Yeah, In the US, CC is estimated that maybe about
a third of the people who would most benefit from
taking PREP, not even like benefit at all, but like
most benefit from taking PREP are taking it sort of
today we are taking it day to day.
Speaker 1 (12:02):
Wait, one third of the people who are at highest
risk for getting HIV are taking it. So two thirds
of the people are.
Speaker 2 (12:09):
Not exactly so, a third r a third arth, two
thirds are not.
Speaker 1 (12:13):
So okay, So there is this idea that PREP is great,
but most people who could most benefit from it don't
take it. One thought as well, if instead of having
to take a pill every day, it was less frequent,
simple behavioral thing, maybe people would do it more often.
And so so there's this search for a for a
(12:35):
new drug that is longer lasting, right, that you in
fact have found spoiler alert, But tell me about the
search for that drug.
Speaker 2 (12:42):
The idea was that HIV has a structural element called
it's capsid, where it encloses the nucleic acid of the
virus within the virus.
Speaker 1 (12:52):
It's it's like it's the bag, right, It's the protein.
Speaker 2 (12:54):
It's yeah, it's a protein coming. It's like a yeah.
And I always want to think it's stronger than the bag.
It's stronger than a bag.
Speaker 1 (13:02):
It's like okay, it like akayas case flask okay, okay.
Speaker 2 (13:07):
And that's the virus is coming into the cell that
opens and dumps the new class ass and out. So
the virus is infecting and when it leaves it encapsulates
the begin and floats away. And targeting that is particularly hard,
and the work on it began a dozen years before
took a dozen years from the work to start before
we've even tested any human being for the first time,
(13:28):
and four thousand molecules were synthesized and screened in test
tubes and animals, selling them other things to be able
to be able to bring forward one to be able
to test in human beings, which then became a lot
of capeer.
Speaker 1 (13:45):
We'll be back in a minute.
Speaker 2 (13:56):
A virus like HIV has a certain number of proteins
that make it function right and caps it had not
been targeted and as a result of a great question
to say, could we target this part of the virus
in a way that it's different. This is important for
HIV broadly because what has been the success of treating
HIV is being able to target the virus in multiple places,
(14:20):
in multiple components of its life cycle, and that is
what makes up a treatment cocktail for HIV. Multiple medications
usually the target different parts of the virus life cycle
at the same time, and from a safety point of view,
actually ones that are very specific to the virus itself
and don't have effects on us. And so a enzyme
(14:43):
that only the virus makes, or in this case, protein
protein interaction that only the virus has, is a great
target because there's nothing that looks like that in our
regular systems.
Speaker 1 (14:56):
So basically that means people are likely to have fewer
side effects because our own cells aren't gonna be bothered.
So it seems like a promising target because it's this
weird thing that the virus does that we don't do.
And then drug researchers find this, this molecule, right, this
potential drug that will eventually be called len.
Speaker 2 (15:14):
A cap of bear.
Speaker 1 (15:15):
But but there's what seems like a problem with this
with this molecule, right, and the problem is that it's
not very soluble in water. It doesn't dissolve well in water.
Tell tell me about that part of it.
Speaker 2 (15:28):
There people who work on it. Just sometimes you do
a lot of work to try to figure out the
best what's got the best attack on the virus itself
around the end time you're trying to target itself. And
then it's not particularly soluble problem because that like medicines
that we take through our mouth, for example, like most
medicine surge IVY need to dissolve an order for us
(15:49):
to absorb them. And actually a lot of work goes
into one one's doing drug development, and maybe you figure
out the thing that targets best, and then you figure
out how to modify it ever as best you can
to be able to absorb it, because if you can't
absorb it doesn't have an effect.
Speaker 1 (16:02):
Right you want you want it to dissolve in water.
You want to take it and then it dissolves and
goes off into your correct exactly.
Speaker 2 (16:11):
It's the tremendous advantage of Lena kaeper beer has been
for what it eventually became is that when it's formulated
as an injection, it forms a deepot of the drug,
well deposit of the drug that dissolves slowly over time
because it isn't immediately soluble.
Speaker 1 (16:31):
And like, was there a moment when somebody sort of
just realized like, oh, this this bug could actually be
you know, like an amazing feature. You know the fact
that it's not soluble, like it might mean we could
give this drug to people and it would last a
really long time.
Speaker 2 (16:46):
I don't think that there's an exact moment. I think
there's actually many moments along the way or a discovery
like this, it's what do we have? How do we
improve on that? Where could we get to? And I
think the I will tell you the very first testing
of lena caprier was not a six month injection.
Speaker 1 (17:02):
So over time, a lot of whiteboards, a lot of
rooms full of people, you get to this idea of oh,
we could do this as an injection that lasts four
months and months.
Speaker 3 (17:11):
Right.
Speaker 2 (17:11):
Yeah.
Speaker 1 (17:12):
So there's two big sort of pivotal trials that you run, right,
tell me about them.
Speaker 2 (17:17):
It's actually an entire program called Purpose And there are
two trials, Purpose one in Purpose two.
Speaker 1 (17:23):
What's the acronym you say, Purpose? I got to ask
you for the acronym.
Speaker 2 (17:26):
Oh, no, so the actually that acronym really is really complicated.
It is not a clear pee you are, so, yeah, no, yeah,
I don't make these up. But the trials are run
across five continents, thousands of people, almost ten thousand people
in total. And the two trials Purpose one and two
(17:48):
were the trials that specifically are phase three pivotal trials
for testing whether something is safe and effective.
Speaker 1 (17:56):
And what were the results?
Speaker 2 (17:58):
Yeah, so Purpose one is among Allison girls and young
women in South Africa Uganda. It's almost five thousand people
in the trial who were either taking the daily pill
or taking the injection. And the among people who were
assigned the injection, zero infections occurred for the primary d
priant of the trial, which had never been seen before
(18:19):
for an HIV prevention trial.
Speaker 1 (18:21):
So okay, so zero absolutely no. One of the two
thousand or so people who got lenni kapavir, none of
them got HIV in the control group. So they were
taking in the control group of the anti retroviral pills
that are standard. Now, how many of those people got HIV.
Speaker 2 (18:40):
For people who are getting the control pill, which is
active prep, the approved active crap, sixteen out of about
one thousand.
Speaker 1 (18:51):
So sixteen out of a thousand is kind of a lot.
This is like over the course of what a year.
Speaker 2 (18:54):
Or something about a year a year follow and in
almost all the cases of the sixteen it's because invested
blood samples from those individuals they weren't using it, and
a testament to for some people how challenging it can
be to use something every day and how something that
(19:15):
injection twice a year for many people both could be
very effective, but also is something that they can make
workable because you can set it and not think about.
Speaker 1 (19:26):
It, Okay, forget it. What's the other What was the
result of the second pivotal trial.
Speaker 2 (19:34):
Yeah, the second pivotal trial was the more geographically diverse
group and was men, transgender women, and men and gender
non binary people in Asia, North and South America and Africa.
It's really broad and global. Yes, And in that study,
again among about two thousand people, there were only two
infections that occurred compared to nine infections among about a
(19:58):
thousand people who received the control so also quite a difference.
Speaker 1 (20:03):
Yes, I mean, presumably the larger audience or the larger
patient population is the people who aren't taking oral prep
at all. Precisely, and you can't randomize ethically to that.
You can't have a control group where it's like we're
not going to give them anything and we're going to
see how they do. But in real life, that is
probably the population you're looking for.
Speaker 2 (20:21):
Right exactly.
Speaker 1 (20:22):
So okay, congratulations on the successful outcome of the trials.
Where are you now?
Speaker 2 (20:29):
Oh so you know, bigger mind we talked about before.
You know, just because science can be the science may
be fantastic, you may have a great publication or a
great p value for science, it doesn't mean that people
actually get medicine. And so the medicine when the cover
has been submitted to regulatory agencies, because drug approvals.
Speaker 4 (20:48):
Are a necessary step for people to receive them, and
that rigorous process is ongoing now and regulatory parentcies all
around the world.
Speaker 2 (20:58):
From the beginning, the thought has been for loutic cover
that's a medicine that can have a global impact, and
then readying for being able to make it and distribute
it for people all around the world. As we have
been doing all of those steps, the dissemination of the science,
the regulatory submissions, we've been simultaneously making plans for global
(21:21):
access particularly access for low and lower middle income countries,
and that part of the story is as important as
everything else because success for ending HIV is it has
to be a global success.
Speaker 1 (21:32):
Yeah, so let's talk about that. I mean, there's obviously
an interesting history of getting HIV drugs to lower income
countries that largely has been a success. Right, people don't
talk about it that much anymore, but it's a good,
happy story. Ultimately, what's happening with Lena kapavir that in
that context, Yes, the the.
Speaker 2 (21:55):
You know, we talked back about my earlier history and
I remember well when there were no medicines in lower
middle income countries and then when there was, and that
was a delay of years and years. And that's not
unique to HIV. That is for innovations and health in general,
that it can take years or decades for medicines to
make it from when they're discovered to even approval and
(22:19):
then availability in low income countries. For lenikapavier years ahead
of results, truly years ahead before we had results. We
were thinking about how we can compress that calendar, and
that included within weeks of the Purpose trials reading out
(22:40):
an announcement that we'd signed voluntary license agreements which are
which allow a generic manufacturer to make a version of
the medicine. So would volntarize de agreees with six generic
manufacturers covering one hundred and twenty countries low and lower
mediome countries to be able to make generic versions in
the medicines royalty free and no profit real that as
(23:02):
soon as they're able to, so as soon as they
can ramp up their technical capacity to be able to
make these medicines.
Speaker 1 (23:10):
So it will be cheap for people in four parts
of the world. And what does that mean sub Saharan Africa,
parts of Asia exactly? What about well, what's it going
to cost in the US? And how does how does
like insurance work for PREP? Insurance cover PREP.
Speaker 2 (23:25):
So insurance dots cover PREP in the United States. And
the CDC has done really extensive analysis yes, to summarize
a lot of really good signs there their conclusions that
access to PREP is not limited by insurance coverage, that
there are two thirds of people who could most benefit
using PREP. That's not for insurance reasons, that is for
(23:45):
all kinds of the other reasons that we talked about
of stigma and and I think that's a strategy looking
forward to to len ACAFA. It's not proved yet United States,
so there's not both insurance coverage and other things are
not said yet. Those don't happen until the FDA is
able to do their rigorous assessment about the efficating and
safety of the medicine.
Speaker 1 (24:04):
So, Okay, you've been working on HIV for for a
long time now, right for deaths, And I'm curious when
you sort of take the long view and you step back,
what do you see?
Speaker 2 (24:15):
Oh, you know, I have been doing this for a
long time, and what has always motivated me is you
know it is actually ending the epidemic.
Speaker 1 (24:25):
When you say ending the epidemic, I mean like I
think of a vaccine and a global eradication campaign. Is
that what you mean when you say that.
Speaker 2 (24:34):
I want to stop new infections. I want to be
able to stop my infections as much as we can.
I want to have treatments that are availed to every
person living with HIV that allow them to live a
full life, and as a result, turning off the tap
of new infections, treating effectively the infections that are existing,
then the public health emergency diminishes, and the cloud that
(24:59):
is ACHIV on the world.
Speaker 1 (25:04):
We'll be back in a minute with the lighting round.
You have undergraduate degrees, as I understand it, in both
biochemistry and comparative religion. Which religions did you compare in
which one.
Speaker 2 (25:24):
One one one?
Speaker 1 (25:28):
Which one lost?
Speaker 2 (25:30):
Now I have an undergraduator in comparative religion, which I love.
I love the interface of society and health, society and
person of religion. Degree was a great way to get out.
Speaker 1 (25:41):
I mean, tell me one thing, like what were you
actually interested in?
Speaker 2 (25:45):
What? What? Like?
Speaker 1 (25:45):
What like? Tell me one thing you learned in studying
comparative religion.
Speaker 2 (25:50):
Oh, I don't many things in comparive religion. I loved.
I love complicated religious texts on how societies have fought
through mystery in the world. I loved American religions because
there's so much variety in the United States and it
reflects a lot of the energy of the US for
you know, all different directions. I have dynamism of dynamism
(26:13):
of religion, and what religion says about society like still
influences my all of the stuff I do.
Speaker 1 (26:19):
Now, what's your second least favorite virus?
Speaker 2 (26:24):
Second least favorite virus?
Speaker 1 (26:26):
I'm assuming HIV is your least favorite.
Speaker 2 (26:29):
HIV is my well, HIV is my favorite book favorite.
Speaker 1 (26:32):
There's two ways to frame it, right, favorite or least favorite,
kind of the same. What's the number two after HIV?
Speaker 3 (26:38):
Oh?
Speaker 2 (26:39):
Hmm? Flu? Like which one is? I want to like
white from the world. Flu would be great, big impact,
terrible viruses that would be like a Goola Marburg that
we'd love to that I'd love to see remove the world.
All the viral epatitis viruses there's multiples of them that
(27:00):
have tremendous prevalence in the world and don't get as
much attention but kill lots of people. Would be great
to eradic it.
Speaker 1 (27:09):
How many papers have you co authored that quote, Tina Turner?
Speaker 2 (27:13):
Oh, the quote one, Yes, there's one. There's there's one
with a what's love got to do with the title? Yes?
Which is about it was about like the motivations to
take prep right, the motivations to take prep are not
simply because someone waged their finger at you and said
take your medicine. Yeah. Love.
Speaker 1 (27:36):
Jared Baton is senior vice president in virology at Kilead Sciences.
Just a quick note, we'll be off for the next
few weeks on a planned hiatus.
Speaker 2 (27:46):
We'll be back soon.
Speaker 1 (27:47):
Today's show was produced by Gabriel Hunter Chang, edited by
Lydia Jean Kott, and engineered by Sarah Buguer. I'm Jacob Goldstein.
Speaker 2 (27:55):
Thanks for listening.
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