Episode 123
123: Lenacapavir for HIV Prevention
Drs. Anshel Kenkare and Mike Reid share a conversation about the incredible science and current context of lenacapavir for HIV prevention, which was recently approved by the FDA.
Episodes | Consult Notes | Subscribe | Twitter | Merch | febrilepodcast@gmail.com
Febrile is produced with support from the Infectious Diseases Society of America (IDSA)
Transcript
Hi everyone.
Speaker:Welcome to Febrile, a cultured podcast about all things infectious disease.
Speaker:We use consult questions to dive into ID clinical reasoning, diagnostics
Speaker:and antimicrobial management.
Speaker:I'm Sara Dong, your host and a Med Peds ID doc.
Speaker:I'll
Speaker:first introduce Dr. Anshel Kenkare.
Speaker:Anshel is a second year
Speaker:internal medicine resident at the Montefiore Primary Care and
Speaker:Social Internal Medicine Program.
Speaker:He's interested in a career in ID focused on public health
Speaker:and environmental stewardship.
Speaker:Also, joining us today
Speaker:is Dr. Mike Reid.
Speaker:Mike is an Associate
Speaker:Professor at University of California, San Francisco.
Speaker:He currently serves as the Chief Science Officer for PEPFAR in the
Speaker:Bureau of Global Health Security and Diplomacy in the US State Department.
Speaker:He also serves as Associate Director of the Center for Global Health Diplomacy,
Speaker:Delivery, and Economics at UCSF.
Speaker:All right.
Speaker:So as everyone's favorite cultured podcast, we ask our guests to
Speaker:share a little piece of culture.
Speaker:So it's really just something non-medical that makes you happy.
Speaker:Um, so what are you guys bringing today??
Speaker:Oh, I can start.
Speaker:Yeah.
Speaker:Yeah.
Speaker:A long time listener, first time caller.
Speaker:So excited.
Speaker:Um, I think for me, I did a tour of the Southwest National Parks recently.
Speaker:Ooh.
Speaker:and I had a lot of hype around Zion and the Grand Canyon, which were incredible.
Speaker:But I loved Arches the National Park, uh, and I just found it so
Speaker:peaceful and beautiful that I will highly recommend it to everybody.
Speaker:Very cool.
Speaker:That's awesome.
Speaker:So, um, on an outdoors theme, I recently walked the Camino
Speaker:de Santiago in northern Spain.
Speaker:So two weeks ago I was in Northern Spain walking the, the pilgrimage to Santiago.
Speaker:Long days of walking, conversations with strangers from all over the world.
Speaker:It was really restorative.
Speaker:Also a humbling, um, realization of how, uh, how at least I
Speaker:need to feel grounded, um,
Speaker:Hmm.
Speaker:could choose a quiet path.
Speaker:And, um, Spanish tapas, uh, were, were, were very restorative.
Speaker:Um, you can't pour from an empty cup rate, and this was a
Speaker:Yeah.
Speaker:my cup refilled.
Speaker:It was great.
Speaker:Yeah.
Speaker:Oh, that's lovely.
Speaker:Now I wanna go take a walk outside.
Speaker:Um, so, Anshel had reached out with this great idea to have an episode
Speaker:and luckily we had some awesome timing because hot off the press, we
Speaker:have heard about the FDA approval of HIV prevention option lenacapavir.
Speaker:And so we're gonna talk about that today, but I will go ahead and hand
Speaker:it off to Anshel to take us forward.
Speaker:Yeah.
Speaker:Thank you so much.
Speaker:I, I really just wanted to talk to Dr. Reid today a little bit about lenacapavir.
Speaker:So just to start, what is lenacapavir and how well does it work?
Speaker:Yeah, so lenacapavir, um, is a first in class HIV capsid inhibitor.
Speaker:It's a, a novel antiretroviral that targets multiple stages in
Speaker:the HIV lifecycle, including capsid assembly, disassembly, viral release.
Speaker:Um, and for the context of this podcast, it's actually marketed
Speaker:as two different products.
Speaker:There's lenacapavir for treatment, which I think is called Sunlenca in the US.
Speaker:And then, as you alluded to hot off the press, the, the formulation
Speaker:for prevention, which is called Yeztugo, is now available.
Speaker:Um, it's available as an oral tablet.
Speaker:More importantly, as a twice yearly subcutaneous injection.
Speaker:Um, I don't think I'll speak too much about treatment with you today,
Speaker:Anshel, but, um, I'm happy to share more details about the science
Speaker:that has recently emerged around prevention and the use of LEN.
Speaker:Yeah, I think that would be great.
Speaker:Just thinking about how this would potentially apply to a patient.
Speaker:Let's say we have a patient here I'm practicing in the Bronx, uh,
Speaker:who is interested in transitioning from an oral PrEP regimen to
Speaker:lenacapavir after seeing the news.
Speaker:How easily can we switch her?
Speaker:What's, what's the general availability of lenacapavir currently?.
Speaker:Yeah.
Speaker:Maybe I can start by just reviewing the clinical research that has been published
Speaker:that sort of supports its use and then I can answer your questions around its
Speaker:clinical role in a place like the Bronx.
Speaker:Um, so.
Speaker:Uh, late last year, at the end of 2024, the scientists who were
Speaker:working on LEN published two papers: PURPOSE 1 and PURPOSE 2, both
Speaker:published in New England Journal.
Speaker:PURPOSE 1 looked at the role of LEN as a prevention tool for cisgender
Speaker:women in Sub-Saharan Africa.
Speaker:They, they evaluated LEN in a setting of very high HIV incidence
Speaker:in, uh, Uganda and South Africa.
Speaker:And they basically randomized participants to either getting injectable LEN
Speaker:every six months or oral Truvada (emtricitabine-tenofovir disoproxil
Speaker:fumarate), which as you know, is the gold standard for biomedical prevention.
Speaker:Um, and they looked at, uh, outcomes over a 12 month period.
Speaker:And in that study, and this is one, one of the most groundbreaking pieces of science,
Speaker:I think, published in many, many years.
Speaker:They found zero HIV infections in the LEN arm.
Speaker:So an HIV incidence that was statistically indistinguishable from
Speaker:zero, which has never been found before in a, in a prevention trial.
Speaker:For, for the purposes of of your question, I think it's worth just
Speaker:highlighting PURPOSE 2 though.
Speaker:So PURPOSE 2, very similar study design, but this was in men and gender diverse
Speaker:people, mostly in the US I think 60 research sites in the US and then
Speaker:about 30 research sites across Brazil, Thailand, South Africa, Peru, Argentina.
Speaker:Uh, I think there may have been one other country.
Speaker:And again, they randomized individuals in that trial to LEN
Speaker:every 6 months or, oral Truvada.
Speaker:And what they found there, again, was incredibly impressive results.
Speaker:Essentially two infections in the LEN group, um, among 2100 participants.
Speaker:And, and that represented a 96% reduction in HIV risk compared
Speaker:to background incidence.
Speaker:So much higher superiority, uh, as compared to the oral option, uh, Truvada.
Speaker:I think key takeaways, which again, relevant to your patient in the Bronx.
Speaker:Near perfect prevention in in PURPOSE 1, um, a hundred percent efficacy and
Speaker:96% efficacy and statistical superiority in PURPOSE 2 over daily oral PrEP.
Speaker:Um, this is unheard of in, in HIV research.
Speaker:I think the other thing to, to highlight that is, again, relevant to your
Speaker:patient, um, and, and also validated by a fair amount of other research though,
Speaker:is that Truvada, whilst an effective agent is only as good as it is when
Speaker:people take it, um, and in PURPOSE 1, um, many people just didn't take it
Speaker:or they didn't take it continuously during the, the research period.
Speaker:And I think that speaks to the potential value of LEN as something
Speaker:where adherence really isn't the same challenge because you're just getting
Speaker:an injection every six months, and that injection offers sustained protection.
Speaker:I think the other insight that, again, is relevant is just that
Speaker:this is very well tolerated.
Speaker:There were mild injection site reactions, some inflammation, a little bit of pain.
Speaker:But overall almost everybody continued the LEN throughout the research period.
Speaker:So for your patient, in the Bronx, and I will say I was a resident in the Bronx.
Speaker:I totally appreciate that, that that client context.
Speaker:Um, yeah, I think the potential to use this drug is very high.
Speaker:I think this could have a, a really transformative impact for, for folks who
Speaker:are at greatest risk of HIV acquisition.
Speaker:And, and not only those that have a harder time taking pills, everybody,
Speaker:the research shows everybody benefited.
Speaker:Two, two things I'll say.
Speaker:And then I'll let you ask your next question Anshel, um.
Speaker:PURPOSE 1 and PURPOSE 2 are just two trials in a family of trials that
Speaker:the drug company have sponsored.
Speaker:Um, three, four, and five.
Speaker:PURPOSE 3, 4, and 5 will explore the role of LEN in cisgendered people in the US.
Speaker:I think that's three.
Speaker:Um, PURPOSE 4 is looking at LEN in people who inject injection drugs And PURPOSE 5
Speaker:is looking at LEN in Europe and the UK.
Speaker:So there are still some important unknowns about its potential
Speaker:impact in those populations.
Speaker:Look, I would imagine that it will be very efficacious in those contexts too.
Speaker:But, but we will wait on those data that some of which will be
Speaker:published pretty soon to confirm that.
Speaker:The other answer to your question though, about is it a good option for somebody
Speaker:in the Bronx, is, um, is it available?
Speaker:Right?
Speaker:And, and I think this is the really exciting thing.
Speaker:So on June 18th, the FDA approved LEN for, for prevention, um,
Speaker:under the brand name, Yeztugo.
Speaker:Um, I dunno how they come up with these names for new drugs, but it is what it is.
Speaker:And I think people have started to prescribe, I think the first drug
Speaker:prescription was soon thereafter.
Speaker:Nonetheless, I think a major challenge is, is ensuring that insurance
Speaker:companies and, and patient assistance programs make the drug available.
Speaker:I understand that Gilead have, have committed to broad access.
Speaker:They have like an advance access program to reduce costs for, for clients.
Speaker:Um, but I imagine that it'll be a few months before it's actually available
Speaker:and on insurance schemes, et cetera.
Speaker:The last thing I'll say, and I'm I'm not an expert on, on drug pricing
Speaker:in the US, but think it will be quite expensive to begin with.
Speaker:The reports I've read are that in the US, Yeztugo will, will be priced
Speaker:annually at between $28,000 and $42,000.
Speaker:And so that may be prohibitive for, for some, although I understand that they,
Speaker:they priced it at that, um, level with the expectation that insurance companies will
Speaker:be able to, to cover that for many people.
Speaker:So there's a long answer to your short question.
Speaker:Happy to revisit any of the pieces that weren't clear.
Speaker:No, I think that was extremely clear.
Speaker:I think, it really is amazing, uh, that we have this FDA approval now, and I, I
Speaker:think the cost overall is something that everybody seems to be questioning, but
Speaker:as people start to prescribe, I think we're gonna see, see where it lands
Speaker:and, and kind of advocate from there.
Speaker:I think a similar question, just because you referenced the PURPOSE 1 trial
Speaker:was conducted in Sub-Saharan Africa.
Speaker:If we were in a clinic in rural Uganda, what kind of access to
Speaker:lenacapavir would potentially be seen?
Speaker:And then on top of that, uh, can be a little bit contentious, but how
Speaker:has the PEPFAR freeze and subsequent defunding affected the ability to roll
Speaker:out a drug like lenacapavir, which has been so incredibly effective?
Speaker:Yeah, it's, it's a great question.
Speaker:Well, both, both of those are great questions.
Speaker:I think, um, up until recently there was, there was great optimism that
Speaker:LEN would be widely available in Sub-Saharan Africa, in, in the imminent
Speaker:future, contingent on FDA approval.
Speaker:I think there is still optimism that lenacapavir will be available in
Speaker:Sub-Saharan Africa in the imminent future.
Speaker:But I, I think it's fair to say that the incoming administration have
Speaker:taken a different approach to global health than past administrations,
Speaker:Democratic and Republican.
Speaker:Um, and as you alluded to Anshel, they instituted a, a pause on foreign
Speaker:assistance early in January after President Trump, uh, returned to power.
Speaker:And that pause on foreign assistance has had quite substantial impacts on
Speaker:the program that I'm involved with, PEPFAR, the, the President's Emergency
Speaker:Plan for AIDS relief and specifically, um, we initially saw a pause of all
Speaker:programming, and then quickly thereafter a resumption of life sustaining activities.
Speaker:So, within a few days of that initial pause after January 21st, we were able
Speaker:to resume much of the activity that had been undertaken before that, as long
Speaker:as it was related to care and treatment and other life sustaining activities.
Speaker:However, there was a pause on all prevention activities that were sustained.
Speaker:And that has had an impact on our capacity to support biomedical prevention
Speaker:programming in high burden countries that PEPFAR had previously supported.
Speaker:I'll also say that to execute the programs that we fund has been concomitantly
Speaker:challenged by the dissolution of US AID as one of our implementing agencies.
Speaker:And so whilst some of our programming that has been funded through other US
Speaker:agencies like the CDC has resumed, some of the programmatic activities undertaken
Speaker:by USAID, particularly related to prevention have, have not been resumed.
Speaker:So all of those things have had a big impact.
Speaker:Perhaps we can include in the links to this podcast, some of
Speaker:the great science that has been done to try and evaluate that.
Speaker:Um, there have been 10 or 20, maybe 30 really great modeling papers that have
Speaker:been produced that have tried to assess the impact on the pause in foreign
Speaker:assistance on HIV outcomes, mortality, incidence, as well as on other diseases
Speaker:including tuberculosis, malaria.
Speaker:Um, I just draw your attention to one.
Speaker:There's a great paper that's published in Lancet HIV by Debra ten Brink, at al
Speaker:about three months ago that estimated if that pause was continued after January
Speaker:in perpetuity, then there would be 3 million additional deaths by 2026, um,
Speaker:from HIV, but there are a number of other papers out there that have similarly
Speaker:kind of evaluated either a country level or across Sub-Saharan Africa, the
Speaker:impact of the pause on, on programs.
Speaker:There's even a website you can go to.
Speaker:There's the PEPFAR Impact Counter website, which is produced by colleagues
Speaker:at Boston University that tries to track in real time the, the impact of
Speaker:these pauses on, on clinical programs.
Speaker:And I, again, I think we might be able to share the link to
Speaker:that in the notes to the podcast.
Speaker:Um, so that all brings me back to, to your question around the, the person in Uganda,
Speaker:um, who, who would be interested in LEN.
Speaker:And I think the question is no, right now, there is no ability to make LEN available.
Speaker:Um, uh, for a couple of reasons.
Speaker:One is that we're still in this place where the current administration haven't
Speaker:determined what their policy is vis-a-vis, um, supporting prevention programming.
Speaker:And two, because the drug is not yet available in Sub-Saharan Africa
Speaker:and, and at a point where it is, the question remains as to whether it'll be
Speaker:affordable for, for ministries of health to procure with their own resources.
Speaker:Maybe I'll just reflect on, on, on some other data that has been published
Speaker:that speaks to the excitement and I think, desire of, of, of recipients
Speaker:of care in Sub-Saharan Africa to, to access long-acting agents.
Speaker:So there's a, a research group, um, actually from the University
Speaker:of California, San Francisco, the SEARCH (Sustainable East Africa
Speaker:Research in Community Health) group that work in Kenya and Uganda.
Speaker:And they have looked at willingness of individuals to switch from Truvada
Speaker:to Cabotegravir, which is another long-acting agent, and, and found that
Speaker:in that setting almost everybody, the vast majority of people when given the
Speaker:choice moved from oral to injectable.
Speaker:And one would anticipate that the same is true for LEN.
Speaker:That if available it will be willingly and excitedly pursued by
Speaker:individuals who would benefit from it.
Speaker:And we can spend a little bit of time, uh, dwelling on this
Speaker:next reflection if it's useful.
Speaker:But I think one of the key issues for Sub-Saharan Africa is, is not
Speaker:so much related to the efficacy.
Speaker:We know based off of PURPOSE 1, that this is incredibly efficacious drug
Speaker:for prevention, but really the cost effectiveness and the cost effectiveness
Speaker:will be determined by what price LEN is available at and, and the
Speaker:volumes that are, are procured to ensure that that price is affordable.
Speaker:And then also the incidence.
Speaker:So there is a fair amount of modeling that's also been done to try and
Speaker:anticipate where LEN will have the greatest impact in high burden settings.
Speaker:I think initial rollout modeling suggests that if we were able to roll out between
Speaker:one and 6 million person years of LEN over a three year period, then that
Speaker:could avert up to a hundred thousand infections in Sub-Saharan Africa.
Speaker:That's actually a, a relatively small fraction of the global
Speaker:incidence, but it's a vital step towards sort of a broader adoption.
Speaker:The places where LEN will be most cost effective are the
Speaker:places of highest incidence.
Speaker:So in Sub-Saharan Africa, that really will mean um, South
Speaker:Africa, which has the highest HIV incidence in Sub-Saharan Africa.
Speaker:And there, there are a number of districts with very high incidence where we, you
Speaker:know, ideally LEN would be targeted.
Speaker:And then there are other smaller pockets in many other countries in
Speaker:Sub-Saharan Africa where if targeted to the right priority populations,
Speaker:it would again be, be cost effective.
Speaker:Um.
Speaker:then similarly in the Philippines, you may know that there's a sort of
Speaker:a, a really rapidly unfolding HIV epidemic in the Philippines right now.
Speaker:And that would be a place where there would be a likelihood of
Speaker:high impact in the near term.
Speaker:The other thing to say is that, that impact will, will, right,
Speaker:will diminish over time, right?
Speaker:So that as incidence goes down, the cost will go up.
Speaker:That is a sort of a paradox that we would have to deal with.
Speaker:But nonetheless, the key message is that, yes, effective.
Speaker:Yes, cost effective in the right, right settings, and it all
Speaker:comes down to what the price is.
Speaker:And I haven't spoken to the price.
Speaker:I'm happy to.
Speaker:Um, the cost savings potentials exist when the price for LEN
Speaker:is around 40 to $60 per year.
Speaker:LEN would be cost saving in those highest burden settings.
Speaker:Um, and that's compared to, so when they do these assessments of
Speaker:cost effectiveness, they compare it to the, the lifetime cost of
Speaker:antiretroviral therapy, right?
Speaker:So.
Speaker:Because of the amazing work of PEPFAR over the last 20 years, antiretroviral
Speaker:therapy, um, in high burden, low income settings is really cheap.
Speaker:A year's supply of TLD, um, which is tenofovir, lamivudine,
Speaker:dolutegravir costs $40 a year.
Speaker:So it's actually not that expensive an intervention.
Speaker:So if you want a prevention intervention that is more cost effective than
Speaker:ART, then it has to be cheaper than the, you know, 20 years of TLD.
Speaker:And so what that means is cost of, of closer to, to 40 to $60 per year.
Speaker:I have two more reflections and then I'll answer your next
Speaker:question if there is one, Anshel.
Speaker:But, there is some really exciting data that has been shared but not peer
Speaker:reviewed, including a paper that is currently under review with Lancet
Speaker:HIV suggesting that generic drug companies could develop lenacapavir
Speaker:at a cost of less than $25 per person per year, um, in the near future.
Speaker:So what that means is that the cost of the goods, the cost of manufacturing could
Speaker:be reduced substantially from the cost that the originator Gilead are making
Speaker:it at to a really affordable price.
Speaker:$25 a year and $25 a year would be very affordable in many high burden countries.
Speaker:The caveat there is that for the generic drug companies to make it
Speaker:available at that affordable price, they have to be sufficient volumes.
Speaker:Um, they're not gonna make it at $25 per prevention year if only a hundred thousand
Speaker:people in Sub-Saharan Africa are on it.
Speaker:They'll, they'll be able to make it at those cost effective prices when
Speaker:the volumes are really, really high.
Speaker:So when there are more than 10 million people on prevention per year.
Speaker:And so they, we end up in a kind of a chicken egg you know, conundrum where
Speaker:you, you need that early adoption of LEN, probably from procurement of the
Speaker:Gilead formulation, the originator formulation, to start to drive the
Speaker:market so that generics know that there is an appetite for this drug.
Speaker:So they then go out and develop more and do so at a price that is, is affordable.
Speaker:To their credit, Gilead have said we want this drug to be widely available
Speaker:Sub-Saharan Africa, and we are gonna make the, the license available to several
Speaker:different generic drug manufacturers.
Speaker:So I think they've made their license available to six generic drug
Speaker:companies right now who in theory, are gonna be able to run with it,
Speaker:figure out how to make it as, as effectively and cheaply as possible.
Speaker:But those generic companies need a market, right?
Speaker:And they're not gonna jump in unless they know that there is a
Speaker:market for this drug, which brings us back to this challenge that.
Speaker:Who's gonna pay for LEN in the first place.
Speaker:And historically, that has been the US government through PEPFAR,
Speaker:um, as well as the Global Fund, which is a, a multilateral donor
Speaker:initiative that includes funding from the US government, also from
Speaker:many other high income countries.
Speaker:Global Fund have said yes, we are very interested in investing
Speaker:in LEN and they are going to procure it and make it available.
Speaker:Um.
Speaker:I am very hopeful that this US administration sees the value
Speaker:of LEN as a prevention tool that that, um, will help us control the
Speaker:epidemic in Sub-Saharan Africa and is worth investing in, but that,
Speaker:that remains to be seen at this time.
Speaker:If they do, I think, um, the investments from the US Government and Global
Speaker:Fund could be really catalytic in driving down the prices to a point
Speaker:at which they become more affordable.
Speaker:But ultimately, and this is my last reflection, we, we are moving into a
Speaker:different time in global health, where the role of donors like the US government,
Speaker:like Global Fund is, is, is evolving.
Speaker:And there is increasing consensus that many countries, particularly
Speaker:middle income countries, should be funding their own HIV response.
Speaker:Um, and in that context, um, there are, there are many countries in Sub-Saharan
Speaker:Africa with a high HIV burden that that will and should invest more in the,
Speaker:the, the prevention programming that is ongoing in their countries rather than
Speaker:relying on, on donors to support that.
Speaker:And for those countries, I think there is a real challenge here in, in, in terms
Speaker:of persuading them that LEN makes sense, particularly when you are comparing
Speaker:LEN to Truvada, which is less than $40 a year, or to condoms which are very
Speaker:effective and even more affordable, right.
Speaker:Um, and so this is the calculus that ministers of health and ministers of
Speaker:finance have to have to deal with.
Speaker:I'll just say one last thing.
Speaker:Even for those politicians though, the dividend of LEN in, in
Speaker:particular high incidence priority populations is, is very compelling.
Speaker:So if you can target LEN to those pockets of highest incidence, whether
Speaker:those are people who inject drugs, men who have sex with men, professional
Speaker:sex workers, um, and then some, some communities of adolescent girls and
Speaker:young women with high HIV incidence, then you could still have a very impactful
Speaker:and cost effective intervention.
Speaker:The challenge there is to sort of identify those pockets and then with
Speaker:precision, allocate the LEN in, in ways that ensure that you are getting not
Speaker:only clinical bang for your buck, but also, financial bang for your buck.
Speaker:And I, I think there's some really interesting science that we need to, to do
Speaker:there around predictive tools, maybe the role of AI, um, et cetera, in determining
Speaker:how we allocate a drug like LEN.
Speaker:Um.
Speaker:Finally, finally, um, in Sub-Saharan Africa, we have a
Speaker:generalized epidemic, right?
Speaker:It's quite different from the US where we have a, a, an epidemic that is
Speaker:really concentrated in small pockets and in that generalized epidemic in,
Speaker:in Sub-Saharan Africa, the, the risk of HIV acquisition is fairly heterogeneous.
Speaker:Um, and so that makes it harder to determine who, who
Speaker:is gonna benefit most from it.
Speaker:Certainly in priority populations, we know that LEN will have value, but in
Speaker:that, in that heterogeneous context, it's more like finding a needle in a haystack.
Speaker:You do have to scale interventions large to see that benefit when
Speaker:that risk is so heterogeneous.
Speaker:So, which, which again adds to this paradox of where LEN
Speaker:will have the greatest value.
Speaker:That was a really long-winded way of answering your short question,
Speaker:so I hope that got some of the answer that you were after.
Speaker:No, not at all.
Speaker:I, I think that was truly fantastic and I appreciate a lot
Speaker:of the insights you provided.
Speaker:I, I did wanna also highlight specifically, the removal of a hundred
Speaker:thousand people from the pipeline of screening, diagnosis and treatment.
Speaker:So really like taking them entirely out of that pipeline, even though
Speaker:it may seem like a smaller number of people, it goes a long way at
Speaker:curtailing the overall epidemic.
Speaker:I also wanted to highlight some international advocacy organizations
Speaker:that, that really helped push for the generic manufacturing of lenacapavir.
Speaker:Uh, I put a link to the People's Medicine Alliance, uh, and I think that, uh, a
Speaker:lot of countries in Sub-Saharan Africa where this drug was tested, um, had
Speaker:community-based organizations come together and advocate for themselves
Speaker:and, and, and really strongly push for this, as you said, lifesaving drug.
Speaker:And, and we, we talk about it being lifesaving.
Speaker:I do wanna ask if you have any concerns about the use of lenacapavir?
Speaker:We've really highlighted the pros, uh, and, and I think for very good reason.
Speaker:Uh, but anything in the implementation that we need to be conscious of,
Speaker:aside from the cost effectiveness?
Speaker:Yeah, that's a great question.
Speaker:There are a couple of things that are worth highlighting.
Speaker:From a biomedical point of view, I think a potential concern
Speaker:relates to resistance, right?
Speaker:Um, so as a first in class capsid inhibitor, LEN represents a novel
Speaker:mechanism, which also means that, uh, we have limited real world
Speaker:data on resistance patterns, and particularly in settings of imperfect
Speaker:adherence or delayed HIV diagnosis.
Speaker:It remains to be seen, um, whether we need to be concerned about
Speaker:the potential of LEN resistance.
Speaker:I will just add to that a caveat that in Sub-Saharan Africa LEN's
Speaker:not available for treatment.
Speaker:In the near term, if it's available, it will only be
Speaker:available for, for prevention.
Speaker:So, so the.
Speaker:The issue of resistance may not be such a big issue in those settings,
Speaker:but I can imagine that in a place like the US where LEN is going to be used
Speaker:as part of treatment and prevention, then be important to consider, um, the
Speaker:potential development of resistance.
Speaker:And you can mitigate that challenge by ensuring that as it's scaled,
Speaker:it's scaled with safeguards, right?
Speaker:So that that means reliable HIV testing before initiation and then monitoring on,
Speaker:on LEN, um, and, as with anybody's who's on oral Truvada or, or Cabotegravir, they,
Speaker:they need to continue to get tested whilst taking that prevention modality to ensure
Speaker:they haven't developed HIV whilst on the drug and therefore at risk for resistance.
Speaker:I am not so worried about resistance in Sub-Saharan Africa, though.
Speaker:I think that the, the biggest concern for me is really about how do we,
Speaker:how do we get to scale and do so affordably, affordably so that ministries
Speaker:of health are able to procure it.
Speaker:That's the biggest challenge that we probably face in the near
Speaker:term for places where I work.
Speaker:Thank you so much Dr. Reid.
Speaker:I, I just wanted to ask for people who are listening, how did you get into
Speaker:this role and can you describe a little bit more about PEPFAR in general?
Speaker:Sure.
Speaker:I finished residency at arguably the best residency program in the
Speaker:country at, uh, Montefiore Primary Care Social Medicine Program.
Speaker:I'll just throw that out there.
Speaker:Um, and actually knew then that I wanted to do global health.
Speaker:I, I was really interested in issues of justice and equity, um, preferential
Speaker:care for the poor and underserved and, and immediately after residency
Speaker:worked in a PEPFAR program, um,
Speaker:Oh, cool.
Speaker:Africa, first, first living in New York then, moving to
Speaker:and living in, in Botswana.
Speaker:Uh, I'll just mention what PEPFAR is and I'll come back to it again.
Speaker:So, PEPFAR is the President's Emergency Plan for AIDS Relief.
Speaker:It's the US Government's flagship program for assistance for HIV established
Speaker:in 2003 by G.W. Bush and has had an unprecedented impact on the HIV epidemic.
Speaker:More than 25 million people's lives have been saved.
Speaker:More than 20 million people are on treatment right now through PEPFAR and
Speaker:over $110 billion of of aid has gone to partner countries during that period.
Speaker:And.
Speaker:At the time that I did residency, PEPFAR was a very morally compelling
Speaker:program that I wanted to be all in on.
Speaker:And so out of residency, I, I worked in a, a funded program in Manhattan
Speaker:at Columbia University, and then moved to Botswana and, and lived there for,
Speaker:for four years where I worked as a an HIV physician and you know, it was
Speaker:great, like on the one hand, I was able to, to see how care was delivered.
Speaker:I was providing HIV care in rural Botswana, but on the other hand, it
Speaker:was fairly jarring to be in a setting where, um, me as a UK trained, American
Speaker:paid physician was delivering care, while I was surrounded by people
Speaker:who were far better clinicians than me, but didn't have the resources.
Speaker:Um, and it really got me thinking about how do we improve the health
Speaker:systems in these countries so that they're able to respond to HIV.
Speaker:Um, so I did that for five years and, and realized actually I wanted to do more
Speaker:training and I was very interested in how do you optimize health systems in high
Speaker:HIV burden settings and then ended up doing fellowship after five years away.
Speaker:Um, did ID fellowship.
Speaker:By the time I'd finished ID fellowship, I was deep in the weeds on how
Speaker:do you optimize health systems?
Speaker:And, and that led to my subsequent career doing health policy
Speaker:research in the HIV space.
Speaker:Fast forward, uh, 10 years and, and now I work as the Chief
Speaker:Science Officer for PEPFAR.
Speaker:Really trying, trying to deliver on my own ambition to support
Speaker:and improve health systems, um,
Speaker:Yeah.
Speaker:in those countries.
Speaker:Yeah.
Speaker:I just wanted to open up to just a last question for you, Dr. Reid, anything
Speaker:that you can recommend for folks who are interested in global health in the
Speaker:future and folks who are interested in advocating for lenacapavir's
Speaker:implementation broadly going forward.
Speaker:Yeah, brilliant question.
Speaker:I love that question.
Speaker:So, let me zoom out and say I think global health is at an
Speaker:inflection point right now.
Speaker:We're at a point where there is a change of political priorities around
Speaker:the importance of global health.
Speaker:I think political attention is waning.
Speaker:And some of that moral ambition that led to PEPFAR being established is waning
Speaker:in places like the US and, and there is a really important responsibility
Speaker:on people that care about these issues to, to make a loud effective noise in
Speaker:support of initiatives like PEPFAR.
Speaker:PEPFAR has had an incredible impact over the last 20 years.
Speaker:Um, but to sustain that impact, I think does require an ongoing political
Speaker:investment from our leadership.
Speaker:And I, I think this is a, a really critical time for people interested in
Speaker:global health to exercise their advocacy and protesting capabilities to ensure
Speaker:that we continue to prioritize global health in settings like the US which
Speaker:historically has been the funder of substantial global health programming
Speaker:. And so I think there is a considerable value in, in folks like you Anshel
Speaker:telling your congresspeople and, and senators about the importance of PEPFAR.
Speaker:You know, as to the role of lenacapavir, again, there is no doubt that LEN is
Speaker:incredibly efficacious clinically, but but unless we're able to show that it's
Speaker:cost effective, then that that clinical efficacy won't be realized on the
Speaker:ground in the places that need it most.
Speaker:And in order for us to get to that point where it's cost effective, again, I
Speaker:think there is, there is real need for advocacy and ambition to ensure that we
Speaker:procure the volumes necessary in the first instance from Gilead to make it available.
Speaker:Mm.
Speaker:And that motivates the generics to, to, to invest.
Speaker:So the price comes down to a point at which partner governments can afford it.
Speaker:So for all of those reasons, I think there is a role for, for
Speaker:folks like you, advocating for LEN.
Speaker:I'll just say one last thing.
Speaker:Some of these things I write about on my substack, you can find
Speaker:Yeah.
Speaker:about my opinions on this and many other things at reimagineglobalhealth.
Speaker:substack.com.
Speaker:Thanks so much to Anshel and Mike for joining us today.
Speaker:You can find more info on our website, febrilepodcast.com, where
Speaker:we house the Consult Notes, which are written supplements of the
Speaker:episodes with links to references, our library of ID infographics,
Speaker:and a link to our merch store.
Speaker:Febrile is produced with support from the Infectious Diseases Society of America.
Speaker:Please reach out if you have any suggestions for future shows or
Speaker:wanna be more involved with Febrile.
Speaker:Thanks for listening.
Speaker:Stay safe and I'll see you next time.
