1 00:00:04,850 --> 00:00:05,630 Hi everyone. 2 00:00:05,660 --> 00:00:10,040 Welcome to Febrile, a cultured podcast about all things infectious disease. 3 00:00:10,400 --> 00:00:14,270 We use consult questions to dive into ID clinical reasoning, diagnostics 4 00:00:14,270 --> 00:00:15,650 and antimicrobial management. 5 00:00:16,400 --> 00:00:19,500 I'm Sara Dong, your host and a Med Peds ID doc. 6 00:00:20,243 --> 00:00:20,483 I'll 7 00:00:20,483 --> 00:00:22,778 first introduce Dr. Anshel Kenkare. 8 00:00:22,778 --> 00:00:25,073 Anshel is a second year 9 00:00:25,073 --> 00:00:28,457 internal medicine resident at the Montefiore Primary Care and 10 00:00:28,457 --> 00:00:30,017 Social Internal Medicine Program. 11 00:00:30,437 --> 00:00:33,557 He's interested in a career in ID focused on public health 12 00:00:33,557 --> 00:00:34,997 and environmental stewardship. 13 00:00:35,227 --> 00:00:36,457 Also, joining us today 14 00:00:36,457 --> 00:00:38,147 is Dr. Mike Reid. 15 00:00:38,147 --> 00:00:39,837 Mike is an Associate 16 00:00:39,837 --> 00:00:42,897 Professor at University of California, San Francisco. 17 00:00:42,907 --> 00:00:46,837 He currently serves as the Chief Science Officer for PEPFAR in the 18 00:00:46,837 --> 00:00:50,767 Bureau of Global Health Security and Diplomacy in the US State Department. 19 00:00:51,187 --> 00:00:55,297 He also serves as Associate Director of the Center for Global Health Diplomacy, 20 00:00:55,327 --> 00:00:57,607 Delivery, and Economics at UCSF. 21 00:00:58,108 --> 00:00:58,558 All right. 22 00:00:58,618 --> 00:01:02,998 So as everyone's favorite cultured podcast, we ask our guests to 23 00:01:02,998 --> 00:01:05,008 share a little piece of culture. 24 00:01:05,008 --> 00:01:08,608 So it's really just something non-medical that makes you happy. 25 00:01:09,088 --> 00:01:12,073 Um, so what are you guys bringing today?? 26 00:01:12,555 --> 00:01:13,305 Oh, I can start. 27 00:01:13,305 --> 00:01:13,605 Yeah. 28 00:01:13,845 --> 00:01:14,175 Yeah. 29 00:01:14,745 --> 00:01:17,000 A long time listener, first time caller. 30 00:01:17,100 --> 00:01:18,150 So excited. 31 00:01:18,720 --> 00:01:24,010 Um, I think for me, I did a tour of the Southwest National Parks recently. 32 00:01:24,655 --> 00:01:25,015 Ooh. 33 00:01:25,300 --> 00:01:31,120 and I had a lot of hype around Zion and the Grand Canyon, which were incredible. 34 00:01:31,420 --> 00:01:35,500 But I loved Arches the National Park, uh, and I just found it so 35 00:01:35,500 --> 00:01:39,370 peaceful and beautiful that I will highly recommend it to everybody. 36 00:01:40,585 --> 00:01:41,215 Very cool. 37 00:01:42,325 --> 00:01:42,955 That's awesome. 38 00:01:42,985 --> 00:01:48,025 So, um, on an outdoors theme, I recently walked the Camino 39 00:01:48,025 --> 00:01:50,215 de Santiago in northern Spain. 40 00:01:50,305 --> 00:01:54,485 So two weeks ago I was in Northern Spain walking the, the pilgrimage to Santiago. 41 00:01:55,225 --> 00:01:58,855 Long days of walking, conversations with strangers from all over the world. 42 00:01:58,855 --> 00:02:00,185 It was really restorative. 43 00:02:00,845 --> 00:02:05,565 Also a humbling, um, realization of how, uh, how at least I 44 00:02:05,565 --> 00:02:07,395 need to feel grounded, um, 45 00:02:07,480 --> 00:02:07,560 Hmm. 46 00:02:07,560 --> 00:02:08,660 could choose a quiet path. 47 00:02:08,685 --> 00:02:13,335 And, um, Spanish tapas, uh, were, were, were very restorative. 48 00:02:13,395 --> 00:02:16,005 Um, you can't pour from an empty cup rate, and this was a 49 00:02:16,290 --> 00:02:16,590 Yeah. 50 00:02:16,605 --> 00:02:17,355 my cup refilled. 51 00:02:17,355 --> 00:02:17,685 It was great. 52 00:02:18,480 --> 00:02:18,840 Yeah. 53 00:02:19,185 --> 00:02:20,235 Oh, that's lovely. 54 00:02:20,295 --> 00:02:21,945 Now I wanna go take a walk outside. 55 00:02:23,175 --> 00:02:27,495 Um, so, Anshel had reached out with this great idea to have an episode 56 00:02:27,495 --> 00:02:32,175 and luckily we had some awesome timing because hot off the press, we 57 00:02:32,445 --> 00:02:36,485 have heard about the FDA approval of HIV prevention option lenacapavir. 58 00:02:36,895 --> 00:02:40,135 And so we're gonna talk about that today, but I will go ahead and hand 59 00:02:40,135 --> 00:02:42,175 it off to Anshel to take us forward. 60 00:02:42,428 --> 00:02:42,698 Yeah. 61 00:02:42,758 --> 00:02:43,628 Thank you so much. 62 00:02:43,688 --> 00:02:48,778 I, I really just wanted to talk to Dr. Reid today a little bit about lenacapavir. 63 00:02:49,128 --> 00:02:53,328 So just to start, what is lenacapavir and how well does it work? 64 00:02:54,993 --> 00:02:59,253 Yeah, so lenacapavir, um, is a first in class HIV capsid inhibitor. 65 00:02:59,623 --> 00:03:03,973 It's a, a novel antiretroviral that targets multiple stages in 66 00:03:03,973 --> 00:03:09,113 the HIV lifecycle, including capsid assembly, disassembly, viral release. 67 00:03:09,773 --> 00:03:15,293 Um, and for the context of this podcast, it's actually marketed 68 00:03:15,293 --> 00:03:17,468 as two different products. 69 00:03:17,468 --> 00:03:22,178 There's lenacapavir for treatment, which I think is called Sunlenca in the US. 70 00:03:22,178 --> 00:03:26,748 And then, as you alluded to hot off the press, the, the formulation 71 00:03:26,748 --> 00:03:31,068 for prevention, which is called Yeztugo, is now available. 72 00:03:31,338 --> 00:03:33,408 Um, it's available as an oral tablet. 73 00:03:33,903 --> 00:03:38,163 More importantly, as a twice yearly subcutaneous injection. 74 00:03:38,613 --> 00:03:41,973 Um, I don't think I'll speak too much about treatment with you today, 75 00:03:41,973 --> 00:03:46,783 Anshel, but, um, I'm happy to share more details about the science 76 00:03:46,783 --> 00:03:51,013 that has recently emerged around prevention and the use of LEN. 77 00:03:51,343 --> 00:03:52,813 Yeah, I think that would be great. 78 00:03:52,913 --> 00:03:56,063 Just thinking about how this would potentially apply to a patient. 79 00:03:56,093 --> 00:03:59,783 Let's say we have a patient here I'm practicing in the Bronx, uh, 80 00:04:00,503 --> 00:04:05,273 who is interested in transitioning from an oral PrEP regimen to 81 00:04:05,273 --> 00:04:06,858 lenacapavir after seeing the news. 82 00:04:07,943 --> 00:04:09,803 How easily can we switch her? 83 00:04:09,833 --> 00:04:12,893 What's, what's the general availability of lenacapavir currently?. 84 00:04:13,613 --> 00:04:14,063 Yeah. 85 00:04:14,673 --> 00:04:19,893 Maybe I can start by just reviewing the clinical research that has been published 86 00:04:19,893 --> 00:04:23,343 that sort of supports its use and then I can answer your questions around its 87 00:04:23,343 --> 00:04:26,073 clinical role in a place like the Bronx. 88 00:04:26,163 --> 00:04:27,978 Um, so. 89 00:04:28,573 --> 00:04:32,593 Uh, late last year, at the end of 2024, the scientists who were 90 00:04:32,593 --> 00:04:40,163 working on LEN published two papers: PURPOSE 1 and PURPOSE 2, both 91 00:04:40,163 --> 00:04:41,543 published in New England Journal. 92 00:04:41,763 --> 00:04:47,913 PURPOSE 1 looked at the role of LEN as a prevention tool for cisgender 93 00:04:47,913 --> 00:04:49,533 women in Sub-Saharan Africa. 94 00:04:49,772 --> 00:04:54,602 They, they evaluated LEN in a setting of very high HIV incidence 95 00:04:54,622 --> 00:04:56,512 in, uh, Uganda and South Africa. 96 00:04:56,512 --> 00:05:01,222 And they basically randomized participants to either getting injectable LEN 97 00:05:01,222 --> 00:05:03,472 every six months or oral Truvada (emtricitabine-tenofovir disoproxil 98 00:05:03,472 --> 00:05:07,407 fumarate), which as you know, is the gold standard for biomedical prevention. 99 00:05:07,677 --> 00:05:10,707 Um, and they looked at, uh, outcomes over a 12 month period. 100 00:05:11,397 --> 00:05:16,197 And in that study, and this is one, one of the most groundbreaking pieces of science, 101 00:05:16,197 --> 00:05:18,507 I think, published in many, many years. 102 00:05:18,507 --> 00:05:21,477 They found zero HIV infections in the LEN arm. 103 00:05:21,837 --> 00:05:26,067 So an HIV incidence that was statistically indistinguishable from 104 00:05:26,067 --> 00:05:29,877 zero, which has never been found before in a, in a prevention trial. 105 00:05:30,357 --> 00:05:33,717 For, for the purposes of of your question, I think it's worth just 106 00:05:33,717 --> 00:05:35,607 highlighting PURPOSE 2 though. 107 00:05:35,967 --> 00:05:41,357 So PURPOSE 2, very similar study design, but this was in men and gender diverse 108 00:05:41,357 --> 00:05:45,537 people, mostly in the US I think 60 research sites in the US and then 109 00:05:45,537 --> 00:05:53,462 about 30 research sites across Brazil, Thailand, South Africa, Peru, Argentina. 110 00:05:53,552 --> 00:05:55,412 Uh, I think there may have been one other country. 111 00:05:55,832 --> 00:05:59,822 And again, they randomized individuals in that trial to LEN 112 00:05:59,822 --> 00:06:02,682 every 6 months or, oral Truvada. 113 00:06:02,972 --> 00:06:06,422 And what they found there, again, was incredibly impressive results. 114 00:06:06,782 --> 00:06:13,082 Essentially two infections in the LEN group, um, among 2100 participants. 115 00:06:13,372 --> 00:06:18,322 And, and that represented a 96% reduction in HIV risk compared 116 00:06:18,322 --> 00:06:19,892 to background incidence. 117 00:06:20,212 --> 00:06:26,012 So much higher superiority, uh, as compared to the oral option, uh, Truvada. 118 00:06:26,822 --> 00:06:30,352 I think key takeaways, which again, relevant to your patient in the Bronx. 119 00:06:30,982 --> 00:06:37,342 Near perfect prevention in in PURPOSE 1, um, a hundred percent efficacy and 120 00:06:37,342 --> 00:06:43,462 96% efficacy and statistical superiority in PURPOSE 2 over daily oral PrEP. 121 00:06:43,492 --> 00:06:46,222 Um, this is unheard of in, in HIV research. 122 00:06:46,242 --> 00:06:50,085 I think the other thing to, to highlight that is, again, relevant to your 123 00:06:50,085 --> 00:06:54,870 patient, um, and, and also validated by a fair amount of other research though, 124 00:06:54,870 --> 00:07:00,240 is that Truvada, whilst an effective agent is only as good as it is when 125 00:07:00,240 --> 00:07:04,470 people take it, um, and in PURPOSE 1, um, many people just didn't take it 126 00:07:04,470 --> 00:07:08,140 or they didn't take it continuously during the, the research period. 127 00:07:08,674 --> 00:07:12,090 And I think that speaks to the potential value of LEN as something 128 00:07:12,090 --> 00:07:15,720 where adherence really isn't the same challenge because you're just getting 129 00:07:15,720 --> 00:07:20,510 an injection every six months, and that injection offers sustained protection. 130 00:07:20,970 --> 00:07:23,710 I think the other insight that, again, is relevant is just that 131 00:07:24,040 --> 00:07:25,720 this is very well tolerated. 132 00:07:25,720 --> 00:07:29,840 There were mild injection site reactions, some inflammation, a little bit of pain. 133 00:07:30,140 --> 00:07:34,860 But overall almost everybody continued the LEN throughout the research period. 134 00:07:35,190 --> 00:07:40,790 So for your patient, in the Bronx, and I will say I was a resident in the Bronx. 135 00:07:40,790 --> 00:07:44,470 I totally appreciate that, that that client context. 136 00:07:44,530 --> 00:07:48,415 Um, yeah, I think the potential to use this drug is very high. 137 00:07:48,415 --> 00:07:52,465 I think this could have a, a really transformative impact for, for folks who 138 00:07:52,465 --> 00:07:54,805 are at greatest risk of HIV acquisition. 139 00:07:55,165 --> 00:07:58,525 And, and not only those that have a harder time taking pills, everybody, 140 00:07:58,525 --> 00:08:00,385 the research shows everybody benefited. 141 00:08:01,400 --> 00:08:02,635 Two, two things I'll say. 142 00:08:02,685 --> 00:08:05,895 And then I'll let you ask your next question Anshel, um. 143 00:08:06,900 --> 00:08:11,650 PURPOSE 1 and PURPOSE 2 are just two trials in a family of trials that 144 00:08:11,735 --> 00:08:14,015 the drug company have sponsored. 145 00:08:14,375 --> 00:08:16,535 Um, three, four, and five. 146 00:08:16,535 --> 00:08:23,095 PURPOSE 3, 4, and 5 will explore the role of LEN in cisgendered people in the US. 147 00:08:23,095 --> 00:08:24,085 I think that's three. 148 00:08:24,175 --> 00:08:29,445 Um, PURPOSE 4 is looking at LEN in people who inject injection drugs And PURPOSE 5 149 00:08:29,445 --> 00:08:32,495 is looking at LEN in Europe and the UK. 150 00:08:32,495 --> 00:08:36,255 So there are still some important unknowns about its potential 151 00:08:36,255 --> 00:08:37,725 impact in those populations. 152 00:08:37,905 --> 00:08:41,925 Look, I would imagine that it will be very efficacious in those contexts too. 153 00:08:41,925 --> 00:08:45,045 But, but we will wait on those data that some of which will be 154 00:08:45,045 --> 00:08:47,595 published pretty soon to confirm that. 155 00:08:47,805 --> 00:08:54,010 The other answer to your question though, about is it a good option for somebody 156 00:08:54,010 --> 00:08:56,740 in the Bronx, is, um, is it available? 157 00:08:56,740 --> 00:08:57,070 Right? 158 00:08:57,130 --> 00:08:59,530 And, and I think this is the really exciting thing. 159 00:08:59,530 --> 00:09:06,610 So on June 18th, the FDA approved LEN for, for prevention, um, 160 00:09:06,910 --> 00:09:08,900 under the brand name, Yeztugo. 161 00:09:09,160 --> 00:09:13,420 Um, I dunno how they come up with these names for new drugs, but it is what it is. 162 00:09:13,765 --> 00:09:17,425 And I think people have started to prescribe, I think the first drug 163 00:09:17,425 --> 00:09:19,045 prescription was soon thereafter. 164 00:09:19,165 --> 00:09:22,735 Nonetheless, I think a major challenge is, is ensuring that insurance 165 00:09:22,735 --> 00:09:27,175 companies and, and patient assistance programs make the drug available. 166 00:09:27,475 --> 00:09:30,715 I understand that Gilead have, have committed to broad access. 167 00:09:30,715 --> 00:09:36,645 They have like an advance access program to reduce costs for, for clients. 168 00:09:36,915 --> 00:09:41,235 Um, but I imagine that it'll be a few months before it's actually available 169 00:09:41,235 --> 00:09:43,765 and on insurance schemes, et cetera. 170 00:09:44,845 --> 00:09:49,015 The last thing I'll say, and I'm I'm not an expert on, on drug pricing 171 00:09:49,015 --> 00:09:52,945 in the US, but think it will be quite expensive to begin with. 172 00:09:52,995 --> 00:09:59,750 The reports I've read are that in the US, Yeztugo will, will be priced 173 00:09:59,750 --> 00:10:04,110 annually at between $28,000 and $42,000. 174 00:10:04,500 --> 00:10:09,060 And so that may be prohibitive for, for some, although I understand that they, 175 00:10:09,120 --> 00:10:13,020 they priced it at that, um, level with the expectation that insurance companies will 176 00:10:13,020 --> 00:10:15,900 be able to, to cover that for many people. 177 00:10:16,140 --> 00:10:19,020 So there's a long answer to your short question. 178 00:10:19,020 --> 00:10:21,510 Happy to revisit any of the pieces that weren't clear. 179 00:10:23,120 --> 00:10:25,580 No, I think that was extremely clear. 180 00:10:25,640 --> 00:10:31,540 I think, it really is amazing, uh, that we have this FDA approval now, and I, I 181 00:10:31,540 --> 00:10:36,930 think the cost overall is something that everybody seems to be questioning, but 182 00:10:36,930 --> 00:10:41,460 as people start to prescribe, I think we're gonna see, see where it lands 183 00:10:41,460 --> 00:10:43,470 and, and kind of advocate from there. 184 00:10:44,050 --> 00:10:47,170 I think a similar question, just because you referenced the PURPOSE 1 trial 185 00:10:47,170 --> 00:10:49,150 was conducted in Sub-Saharan Africa. 186 00:10:49,560 --> 00:10:55,390 If we were in a clinic in rural Uganda, what kind of access to 187 00:10:55,480 --> 00:10:57,910 lenacapavir would potentially be seen? 188 00:10:58,360 --> 00:11:03,520 And then on top of that, uh, can be a little bit contentious, but how 189 00:11:03,520 --> 00:11:08,770 has the PEPFAR freeze and subsequent defunding affected the ability to roll 190 00:11:08,770 --> 00:11:12,280 out a drug like lenacapavir, which has been so incredibly effective? 191 00:11:12,848 --> 00:11:14,138 Yeah, it's, it's a great question. 192 00:11:14,138 --> 00:11:16,058 Well, both, both of those are great questions. 193 00:11:16,108 --> 00:11:20,903 I think, um, up until recently there was, there was great optimism that 194 00:11:20,903 --> 00:11:25,253 LEN would be widely available in Sub-Saharan Africa, in, in the imminent 195 00:11:25,253 --> 00:11:28,193 future, contingent on FDA approval. 196 00:11:28,530 --> 00:11:35,130 I think there is still optimism that lenacapavir will be available in 197 00:11:35,130 --> 00:11:37,170 Sub-Saharan Africa in the imminent future. 198 00:11:38,310 --> 00:11:45,375 But I, I think it's fair to say that the incoming administration have 199 00:11:45,435 --> 00:11:50,055 taken a different approach to global health than past administrations, 200 00:11:50,105 --> 00:11:51,665 Democratic and Republican. 201 00:11:52,115 --> 00:11:56,905 Um, and as you alluded to Anshel, they instituted a, a pause on foreign 202 00:11:56,905 --> 00:12:01,815 assistance early in January after President Trump, uh, returned to power. 203 00:12:02,195 --> 00:12:06,635 And that pause on foreign assistance has had quite substantial impacts on 204 00:12:07,155 --> 00:12:10,515 the program that I'm involved with, PEPFAR, the, the President's Emergency 205 00:12:10,515 --> 00:12:15,255 Plan for AIDS relief and specifically, um, we initially saw a pause of all 206 00:12:15,255 --> 00:12:20,285 programming, and then quickly thereafter a resumption of life sustaining activities. 207 00:12:20,285 --> 00:12:24,795 So, within a few days of that initial pause after January 21st, we were able 208 00:12:24,795 --> 00:12:29,515 to resume much of the activity that had been undertaken before that, as long 209 00:12:29,515 --> 00:12:35,095 as it was related to care and treatment and other life sustaining activities. 210 00:12:35,880 --> 00:12:42,010 However, there was a pause on all prevention activities that were sustained. 211 00:12:42,360 --> 00:12:48,420 And that has had an impact on our capacity to support biomedical prevention 212 00:12:48,420 --> 00:12:53,040 programming in high burden countries that PEPFAR had previously supported. 213 00:12:53,190 --> 00:13:00,465 I'll also say that to execute the programs that we fund has been concomitantly 214 00:13:00,465 --> 00:13:06,495 challenged by the dissolution of US AID as one of our implementing agencies. 215 00:13:06,495 --> 00:13:10,145 And so whilst some of our programming that has been funded through other US 216 00:13:10,145 --> 00:13:14,795 agencies like the CDC has resumed, some of the programmatic activities undertaken 217 00:13:14,795 --> 00:13:19,355 by USAID, particularly related to prevention have, have not been resumed. 218 00:13:20,225 --> 00:13:22,285 So all of those things have had a big impact. 219 00:13:22,385 --> 00:13:25,545 Perhaps we can include in the links to this podcast, some of 220 00:13:25,545 --> 00:13:28,935 the great science that has been done to try and evaluate that. 221 00:13:29,325 --> 00:13:34,613 Um, there have been 10 or 20, maybe 30 really great modeling papers that have 222 00:13:34,613 --> 00:13:39,748 been produced that have tried to assess the impact on the pause in foreign 223 00:13:39,748 --> 00:13:45,368 assistance on HIV outcomes, mortality, incidence, as well as on other diseases 224 00:13:45,398 --> 00:13:47,718 including tuberculosis, malaria. 225 00:13:48,048 --> 00:13:50,178 Um, I just draw your attention to one. 226 00:13:50,178 --> 00:13:55,283 There's a great paper that's published in Lancet HIV by Debra ten Brink, at al 227 00:13:55,673 --> 00:14:01,523 about three months ago that estimated if that pause was continued after January 228 00:14:01,713 --> 00:14:07,003 in perpetuity, then there would be 3 million additional deaths by 2026, um, 229 00:14:07,003 --> 00:14:10,753 from HIV, but there are a number of other papers out there that have similarly 230 00:14:10,813 --> 00:14:14,293 kind of evaluated either a country level or across Sub-Saharan Africa, the 231 00:14:14,293 --> 00:14:16,833 impact of the pause on, on programs. 232 00:14:17,133 --> 00:14:18,813 There's even a website you can go to. 233 00:14:18,813 --> 00:14:23,738 There's the PEPFAR Impact Counter website, which is produced by colleagues 234 00:14:23,738 --> 00:14:27,338 at Boston University that tries to track in real time the, the impact of 235 00:14:27,338 --> 00:14:29,498 these pauses on, on clinical programs. 236 00:14:29,498 --> 00:14:32,378 And I, again, I think we might be able to share the link to 237 00:14:32,378 --> 00:14:34,158 that in the notes to the podcast. 238 00:14:34,948 --> 00:14:40,468 Um, so that all brings me back to, to your question around the, the person in Uganda, 239 00:14:40,468 --> 00:14:43,578 um, who, who would be interested in LEN. 240 00:14:43,724 --> 00:14:48,629 And I think the question is no, right now, there is no ability to make LEN available. 241 00:14:48,929 --> 00:14:50,969 Um, uh, for a couple of reasons. 242 00:14:50,969 --> 00:14:54,739 One is that we're still in this place where the current administration haven't 243 00:14:54,739 --> 00:14:59,329 determined what their policy is vis-a-vis, um, supporting prevention programming. 244 00:14:59,689 --> 00:15:03,094 And two, because the drug is not yet available in Sub-Saharan Africa 245 00:15:03,274 --> 00:15:07,459 and, and at a point where it is, the question remains as to whether it'll be 246 00:15:07,459 --> 00:15:12,109 affordable for, for ministries of health to procure with their own resources. 247 00:15:12,363 --> 00:15:17,013 Maybe I'll just reflect on, on, on some other data that has been published 248 00:15:17,013 --> 00:15:23,509 that speaks to the excitement and I think, desire of, of, of recipients 249 00:15:23,509 --> 00:15:27,289 of care in Sub-Saharan Africa to, to access long-acting agents. 250 00:15:27,619 --> 00:15:31,099 So there's a, a research group, um, actually from the University 251 00:15:31,099 --> 00:15:32,929 of California, San Francisco, the SEARCH (Sustainable East Africa 252 00:15:32,929 --> 00:15:35,749 Research in Community Health) group that work in Kenya and Uganda. 253 00:15:36,009 --> 00:15:40,679 And they have looked at willingness of individuals to switch from Truvada 254 00:15:40,679 --> 00:15:45,329 to Cabotegravir, which is another long-acting agent, and, and found that 255 00:15:45,329 --> 00:15:50,399 in that setting almost everybody, the vast majority of people when given the 256 00:15:50,399 --> 00:15:53,639 choice moved from oral to injectable. 257 00:15:53,639 --> 00:15:56,759 And one would anticipate that the same is true for LEN. 258 00:15:56,789 --> 00:16:02,143 That if available it will be willingly and excitedly pursued by 259 00:16:02,243 --> 00:16:04,063 individuals who would benefit from it. 260 00:16:04,433 --> 00:16:07,663 And we can spend a little bit of time, uh, dwelling on this 261 00:16:07,663 --> 00:16:09,133 next reflection if it's useful. 262 00:16:09,133 --> 00:16:13,363 But I think one of the key issues for Sub-Saharan Africa is, is not 263 00:16:13,603 --> 00:16:16,093 so much related to the efficacy. 264 00:16:16,143 --> 00:16:21,333 We know based off of PURPOSE 1, that this is incredibly efficacious drug 265 00:16:21,333 --> 00:16:26,663 for prevention, but really the cost effectiveness and the cost effectiveness 266 00:16:26,663 --> 00:16:33,193 will be determined by what price LEN is available at and, and the 267 00:16:33,193 --> 00:16:37,873 volumes that are, are procured to ensure that that price is affordable. 268 00:16:38,103 --> 00:16:39,613 And then also the incidence. 269 00:16:39,963 --> 00:16:43,263 So there is a fair amount of modeling that's also been done to try and 270 00:16:43,263 --> 00:16:47,923 anticipate where LEN will have the greatest impact in high burden settings. 271 00:16:48,483 --> 00:16:53,673 I think initial rollout modeling suggests that if we were able to roll out between 272 00:16:53,673 --> 00:16:58,983 one and 6 million person years of LEN over a three year period, then that 273 00:16:58,983 --> 00:17:03,063 could avert up to a hundred thousand infections in Sub-Saharan Africa. 274 00:17:03,423 --> 00:17:06,603 That's actually a, a relatively small fraction of the global 275 00:17:06,603 --> 00:17:11,133 incidence, but it's a vital step towards sort of a broader adoption. 276 00:17:11,503 --> 00:17:16,143 The places where LEN will be most cost effective are the 277 00:17:16,143 --> 00:17:17,723 places of highest incidence. 278 00:17:18,003 --> 00:17:23,118 So in Sub-Saharan Africa, that really will mean um, South 279 00:17:23,118 --> 00:17:26,343 Africa, which has the highest HIV incidence in Sub-Saharan Africa. 280 00:17:26,343 --> 00:17:30,453 And there, there are a number of districts with very high incidence where we, you 281 00:17:30,453 --> 00:17:32,403 know, ideally LEN would be targeted. 282 00:17:32,733 --> 00:17:35,943 And then there are other smaller pockets in many other countries in 283 00:17:35,943 --> 00:17:40,083 Sub-Saharan Africa where if targeted to the right priority populations, 284 00:17:40,083 --> 00:17:42,663 it would again be, be cost effective. 285 00:17:43,083 --> 00:17:43,143 Um. 286 00:17:43,953 --> 00:17:47,103 then similarly in the Philippines, you may know that there's a sort of 287 00:17:47,298 --> 00:17:52,293 a, a really rapidly unfolding HIV epidemic in the Philippines right now. 288 00:17:52,293 --> 00:17:55,233 And that would be a place where there would be a likelihood of 289 00:17:55,233 --> 00:17:56,883 high impact in the near term. 290 00:17:58,288 --> 00:18:02,398 The other thing to say is that, that impact will, will, right, 291 00:18:02,428 --> 00:18:04,108 will diminish over time, right? 292 00:18:04,108 --> 00:18:07,018 So that as incidence goes down, the cost will go up. 293 00:18:07,358 --> 00:18:09,968 That is a sort of a paradox that we would have to deal with. 294 00:18:09,968 --> 00:18:13,088 But nonetheless, the key message is that, yes, effective. 295 00:18:13,898 --> 00:18:17,318 Yes, cost effective in the right, right settings, and it all 296 00:18:17,318 --> 00:18:19,568 comes down to what the price is. 297 00:18:19,838 --> 00:18:20,828 And I haven't spoken to the price. 298 00:18:20,828 --> 00:18:21,518 I'm happy to. 299 00:18:21,848 --> 00:18:26,628 Um, the cost savings potentials exist when the price for LEN 300 00:18:26,698 --> 00:18:29,698 is around 40 to $60 per year. 301 00:18:29,978 --> 00:18:33,993 LEN would be cost saving in those highest burden settings. 302 00:18:34,263 --> 00:18:38,263 Um, and that's compared to, so when they do these assessments of 303 00:18:38,263 --> 00:18:42,583 cost effectiveness, they compare it to the, the lifetime cost of 304 00:18:42,583 --> 00:18:44,473 antiretroviral therapy, right? 305 00:18:44,473 --> 00:18:44,773 So. 306 00:18:45,803 --> 00:18:51,173 Because of the amazing work of PEPFAR over the last 20 years, antiretroviral 307 00:18:51,173 --> 00:18:56,573 therapy, um, in high burden, low income settings is really cheap. 308 00:18:56,883 --> 00:19:00,678 A year's supply of TLD, um, which is tenofovir, lamivudine, 309 00:19:00,678 --> 00:19:03,593 dolutegravir costs $40 a year. 310 00:19:04,493 --> 00:19:07,013 So it's actually not that expensive an intervention. 311 00:19:07,013 --> 00:19:11,153 So if you want a prevention intervention that is more cost effective than 312 00:19:11,403 --> 00:19:16,293 ART, then it has to be cheaper than the, you know, 20 years of TLD. 313 00:19:16,623 --> 00:19:22,223 And so what that means is cost of, of closer to, to 40 to $60 per year. 314 00:19:22,695 --> 00:19:25,190 I have two more reflections and then I'll answer your next 315 00:19:25,190 --> 00:19:26,430 question if there is one, Anshel. 316 00:19:26,450 --> 00:19:32,570 But, there is some really exciting data that has been shared but not peer 317 00:19:32,570 --> 00:19:37,040 reviewed, including a paper that is currently under review with Lancet 318 00:19:37,060 --> 00:19:45,345 HIV suggesting that generic drug companies could develop lenacapavir 319 00:19:45,955 --> 00:19:52,945 at a cost of less than $25 per person per year, um, in the near future. 320 00:19:53,125 --> 00:19:57,385 So what that means is that the cost of the goods, the cost of manufacturing could 321 00:19:57,385 --> 00:20:01,815 be reduced substantially from the cost that the originator Gilead are making 322 00:20:01,815 --> 00:20:03,855 it at to a really affordable price. 323 00:20:04,095 --> 00:20:09,825 $25 a year and $25 a year would be very affordable in many high burden countries. 324 00:20:10,113 --> 00:20:16,023 The caveat there is that for the generic drug companies to make it 325 00:20:16,023 --> 00:20:20,133 available at that affordable price, they have to be sufficient volumes. 326 00:20:20,523 --> 00:20:26,343 Um, they're not gonna make it at $25 per prevention year if only a hundred thousand 327 00:20:26,343 --> 00:20:28,593 people in Sub-Saharan Africa are on it. 328 00:20:28,623 --> 00:20:32,763 They'll, they'll be able to make it at those cost effective prices when 329 00:20:32,763 --> 00:20:34,413 the volumes are really, really high. 330 00:20:34,623 --> 00:20:38,823 So when there are more than 10 million people on prevention per year. 331 00:20:39,598 --> 00:20:44,038 And so they, we end up in a kind of a chicken egg you know, conundrum where 332 00:20:44,368 --> 00:20:50,568 you, you need that early adoption of LEN, probably from procurement of the 333 00:20:50,568 --> 00:20:55,098 Gilead formulation, the originator formulation, to start to drive the 334 00:20:55,098 --> 00:20:58,998 market so that generics know that there is an appetite for this drug. 335 00:20:58,998 --> 00:21:04,218 So they then go out and develop more and do so at a price that is, is affordable. 336 00:21:05,203 --> 00:21:11,173 To their credit, Gilead have said we want this drug to be widely available 337 00:21:11,173 --> 00:21:17,553 Sub-Saharan Africa, and we are gonna make the, the license available to several 338 00:21:17,553 --> 00:21:19,413 different generic drug manufacturers. 339 00:21:19,413 --> 00:21:23,253 So I think they've made their license available to six generic drug 340 00:21:23,253 --> 00:21:26,883 companies right now who in theory, are gonna be able to run with it, 341 00:21:27,093 --> 00:21:31,323 figure out how to make it as, as effectively and cheaply as possible. 342 00:21:31,893 --> 00:21:34,303 But those generic companies need a market, right? 343 00:21:34,303 --> 00:21:36,703 And they're not gonna jump in unless they know that there is a 344 00:21:36,703 --> 00:21:39,373 market for this drug, which brings us back to this challenge that. 345 00:21:40,273 --> 00:21:43,103 Who's gonna pay for LEN in the first place. 346 00:21:43,313 --> 00:21:46,703 And historically, that has been the US government through PEPFAR, 347 00:21:47,003 --> 00:21:51,803 um, as well as the Global Fund, which is a, a multilateral donor 348 00:21:51,803 --> 00:21:54,893 initiative that includes funding from the US government, also from 349 00:21:54,893 --> 00:21:56,363 many other high income countries. 350 00:21:57,143 --> 00:22:01,043 Global Fund have said yes, we are very interested in investing 351 00:22:01,043 --> 00:22:04,913 in LEN and they are going to procure it and make it available. 352 00:22:05,153 --> 00:22:05,573 Um. 353 00:22:06,293 --> 00:22:11,093 I am very hopeful that this US administration sees the value 354 00:22:11,093 --> 00:22:15,653 of LEN as a prevention tool that that, um, will help us control the 355 00:22:15,653 --> 00:22:19,073 epidemic in Sub-Saharan Africa and is worth investing in, but that, 356 00:22:19,073 --> 00:22:20,933 that remains to be seen at this time. 357 00:22:21,333 --> 00:22:25,163 If they do, I think, um, the investments from the US Government and Global 358 00:22:25,163 --> 00:22:29,453 Fund could be really catalytic in driving down the prices to a point 359 00:22:29,453 --> 00:22:31,193 at which they become more affordable. 360 00:22:31,523 --> 00:22:35,963 But ultimately, and this is my last reflection, we, we are moving into a 361 00:22:35,963 --> 00:22:41,133 different time in global health, where the role of donors like the US government, 362 00:22:41,193 --> 00:22:43,803 like Global Fund is, is, is evolving. 363 00:22:44,083 --> 00:22:49,123 And there is increasing consensus that many countries, particularly 364 00:22:49,123 --> 00:22:53,303 middle income countries, should be funding their own HIV response. 365 00:22:53,603 --> 00:22:58,463 Um, and in that context, um, there are, there are many countries in Sub-Saharan 366 00:22:58,463 --> 00:23:04,823 Africa with a high HIV burden that that will and should invest more in the, 367 00:23:04,913 --> 00:23:08,813 the, the prevention programming that is ongoing in their countries rather than 368 00:23:08,813 --> 00:23:11,153 relying on, on donors to support that. 369 00:23:11,573 --> 00:23:16,523 And for those countries, I think there is a real challenge here in, in, in terms 370 00:23:16,523 --> 00:23:20,723 of persuading them that LEN makes sense, particularly when you are comparing 371 00:23:20,913 --> 00:23:27,143 LEN to Truvada, which is less than $40 a year, or to condoms which are very 372 00:23:27,143 --> 00:23:29,603 effective and even more affordable, right. 373 00:23:29,963 --> 00:23:33,863 Um, and so this is the calculus that ministers of health and ministers of 374 00:23:33,863 --> 00:23:36,293 finance have to have to deal with. 375 00:23:36,683 --> 00:23:37,913 I'll just say one last thing. 376 00:23:38,013 --> 00:23:42,503 Even for those politicians though, the dividend of LEN in, in 377 00:23:42,503 --> 00:23:48,023 particular high incidence priority populations is, is very compelling. 378 00:23:48,443 --> 00:23:53,633 So if you can target LEN to those pockets of highest incidence, whether 379 00:23:53,633 --> 00:23:58,483 those are people who inject drugs, men who have sex with men, professional 380 00:23:58,483 --> 00:24:03,553 sex workers, um, and then some, some communities of adolescent girls and 381 00:24:03,553 --> 00:24:08,143 young women with high HIV incidence, then you could still have a very impactful 382 00:24:08,143 --> 00:24:10,663 and cost effective intervention. 383 00:24:10,853 --> 00:24:15,863 The challenge there is to sort of identify those pockets and then with 384 00:24:15,863 --> 00:24:21,353 precision, allocate the LEN in, in ways that ensure that you are getting not 385 00:24:21,353 --> 00:24:25,728 only clinical bang for your buck, but also, financial bang for your buck. 386 00:24:26,088 --> 00:24:30,318 And I, I think there's some really interesting science that we need to, to do 387 00:24:30,318 --> 00:24:36,293 there around predictive tools, maybe the role of AI, um, et cetera, in determining 388 00:24:36,293 --> 00:24:38,563 how we allocate a drug like LEN. 389 00:24:39,313 --> 00:24:39,733 Um. 390 00:24:41,788 --> 00:24:46,018 Finally, finally, um, in Sub-Saharan Africa, we have a 391 00:24:46,018 --> 00:24:47,428 generalized epidemic, right? 392 00:24:47,428 --> 00:24:50,868 It's quite different from the US where we have a, a, an epidemic that is 393 00:24:50,868 --> 00:24:55,678 really concentrated in small pockets and in that generalized epidemic in, 394 00:24:55,678 --> 00:25:01,868 in Sub-Saharan Africa, the, the risk of HIV acquisition is fairly heterogeneous. 395 00:25:02,198 --> 00:25:05,798 Um, and so that makes it harder to determine who, who 396 00:25:05,798 --> 00:25:07,238 is gonna benefit most from it. 397 00:25:07,238 --> 00:25:10,528 Certainly in priority populations, we know that LEN will have value, but in 398 00:25:10,528 --> 00:25:15,188 that, in that heterogeneous context, it's more like finding a needle in a haystack. 399 00:25:15,738 --> 00:25:20,578 You do have to scale interventions large to see that benefit when 400 00:25:20,578 --> 00:25:22,168 that risk is so heterogeneous. 401 00:25:22,168 --> 00:25:24,838 So, which, which again adds to this paradox of where LEN 402 00:25:24,838 --> 00:25:26,068 will have the greatest value. 403 00:25:27,298 --> 00:25:30,718 That was a really long-winded way of answering your short question, 404 00:25:30,718 --> 00:25:33,178 so I hope that got some of the answer that you were after. 405 00:25:33,873 --> 00:25:34,713 No, not at all. 406 00:25:34,878 --> 00:25:38,973 I, I think that was truly fantastic and I appreciate a lot 407 00:25:38,973 --> 00:25:40,803 of the insights you provided. 408 00:25:40,803 --> 00:25:45,913 I, I did wanna also highlight specifically, the removal of a hundred 409 00:25:45,913 --> 00:25:50,873 thousand people from the pipeline of screening, diagnosis and treatment. 410 00:25:51,513 --> 00:25:55,513 So really like taking them entirely out of that pipeline, even though 411 00:25:55,513 --> 00:25:59,653 it may seem like a smaller number of people, it goes a long way at 412 00:25:59,653 --> 00:26:01,963 curtailing the overall epidemic. 413 00:26:02,103 --> 00:26:05,883 I also wanted to highlight some international advocacy organizations 414 00:26:05,883 --> 00:26:11,423 that, that really helped push for the generic manufacturing of lenacapavir. 415 00:26:11,913 --> 00:26:17,703 Uh, I put a link to the People's Medicine Alliance, uh, and I think that, uh, a 416 00:26:17,703 --> 00:26:22,473 lot of countries in Sub-Saharan Africa where this drug was tested, um, had 417 00:26:22,503 --> 00:26:26,193 community-based organizations come together and advocate for themselves 418 00:26:26,193 --> 00:26:30,963 and, and, and really strongly push for this, as you said, lifesaving drug. 419 00:26:31,413 --> 00:26:33,933 And, and we, we talk about it being lifesaving. 420 00:26:33,983 --> 00:26:38,253 I do wanna ask if you have any concerns about the use of lenacapavir? 421 00:26:38,273 --> 00:26:43,103 We've really highlighted the pros, uh, and, and I think for very good reason. 422 00:26:43,433 --> 00:26:47,153 Uh, but anything in the implementation that we need to be conscious of, 423 00:26:47,213 --> 00:26:49,613 aside from the cost effectiveness? 424 00:26:50,768 --> 00:26:51,818 Yeah, that's a great question. 425 00:26:51,868 --> 00:26:53,878 There are a couple of things that are worth highlighting. 426 00:26:53,928 --> 00:26:56,868 From a biomedical point of view, I think a potential concern 427 00:26:56,868 --> 00:26:58,428 relates to resistance, right? 428 00:26:58,848 --> 00:27:04,008 Um, so as a first in class capsid inhibitor, LEN represents a novel 429 00:27:04,058 --> 00:27:08,618 mechanism, which also means that, uh, we have limited real world 430 00:27:08,618 --> 00:27:14,018 data on resistance patterns, and particularly in settings of imperfect 431 00:27:14,018 --> 00:27:16,778 adherence or delayed HIV diagnosis. 432 00:27:17,178 --> 00:27:21,888 It remains to be seen, um, whether we need to be concerned about 433 00:27:22,233 --> 00:27:24,843 the potential of LEN resistance. 434 00:27:25,923 --> 00:27:30,273 I will just add to that a caveat that in Sub-Saharan Africa LEN's 435 00:27:30,273 --> 00:27:32,283 not available for treatment. 436 00:27:32,483 --> 00:27:35,408 In the near term, if it's available, it will only be 437 00:27:35,408 --> 00:27:37,178 available for, for prevention. 438 00:27:37,178 --> 00:27:38,498 So, so the. 439 00:27:38,873 --> 00:27:43,963 The issue of resistance may not be such a big issue in those settings, 440 00:27:43,963 --> 00:27:48,463 but I can imagine that in a place like the US where LEN is going to be used 441 00:27:48,463 --> 00:27:53,183 as part of treatment and prevention, then be important to consider, um, the 442 00:27:53,183 --> 00:27:55,583 potential development of resistance. 443 00:27:55,973 --> 00:27:59,823 And you can mitigate that challenge by ensuring that as it's scaled, 444 00:27:59,823 --> 00:28:01,323 it's scaled with safeguards, right? 445 00:28:01,323 --> 00:28:06,843 So that that means reliable HIV testing before initiation and then monitoring on, 446 00:28:07,133 --> 00:28:15,943 on LEN, um, and, as with anybody's who's on oral Truvada or, or Cabotegravir, they, 447 00:28:16,003 --> 00:28:22,243 they need to continue to get tested whilst taking that prevention modality to ensure 448 00:28:22,243 --> 00:28:27,833 they haven't developed HIV whilst on the drug and therefore at risk for resistance. 449 00:28:28,998 --> 00:28:32,088 I am not so worried about resistance in Sub-Saharan Africa, though. 450 00:28:32,478 --> 00:28:36,348 I think that the, the biggest concern for me is really about how do we, 451 00:28:36,468 --> 00:28:40,548 how do we get to scale and do so affordably, affordably so that ministries 452 00:28:40,548 --> 00:28:43,058 of health are able to procure it. 453 00:28:43,128 --> 00:28:46,208 That's the biggest challenge that we probably face in the near 454 00:28:46,208 --> 00:28:48,068 term for places where I work. 455 00:28:48,566 --> 00:28:49,551 Thank you so much Dr. Reid. 456 00:28:49,706 --> 00:28:55,236 I, I just wanted to ask for people who are listening, how did you get into 457 00:28:55,296 --> 00:28:59,616 this role and can you describe a little bit more about PEPFAR in general? 458 00:28:59,973 --> 00:29:00,543 Sure. 459 00:29:00,693 --> 00:29:05,043 I finished residency at arguably the best residency program in the 460 00:29:05,043 --> 00:29:08,313 country at, uh, Montefiore Primary Care Social Medicine Program. 461 00:29:08,313 --> 00:29:09,333 I'll just throw that out there. 462 00:29:09,783 --> 00:29:12,633 Um, and actually knew then that I wanted to do global health. 463 00:29:12,633 --> 00:29:17,823 I, I was really interested in issues of justice and equity, um, preferential 464 00:29:17,823 --> 00:29:22,533 care for the poor and underserved and, and immediately after residency 465 00:29:22,533 --> 00:29:26,223 worked in a PEPFAR program, um, 466 00:29:26,338 --> 00:29:26,798 Oh, cool. 467 00:29:27,213 --> 00:29:32,523 Africa, first, first living in New York then, moving to 468 00:29:32,523 --> 00:29:34,283 and living in, in Botswana. 469 00:29:35,693 --> 00:29:38,943 Uh, I'll just mention what PEPFAR is and I'll come back to it again. 470 00:29:38,943 --> 00:29:42,093 So, PEPFAR is the President's Emergency Plan for AIDS Relief. 471 00:29:42,093 --> 00:29:48,633 It's the US Government's flagship program for assistance for HIV established 472 00:29:48,633 --> 00:29:55,313 in 2003 by G.W. Bush and has had an unprecedented impact on the HIV epidemic. 473 00:29:55,313 --> 00:29:57,623 More than 25 million people's lives have been saved. 474 00:29:57,673 --> 00:30:01,423 More than 20 million people are on treatment right now through PEPFAR and 475 00:30:01,423 --> 00:30:06,313 over $110 billion of of aid has gone to partner countries during that period. 476 00:30:07,123 --> 00:30:07,483 And. 477 00:30:08,738 --> 00:30:14,378 At the time that I did residency, PEPFAR was a very morally compelling 478 00:30:14,428 --> 00:30:16,978 program that I wanted to be all in on. 479 00:30:17,595 --> 00:30:21,975 And so out of residency, I, I worked in a, a funded program in Manhattan 480 00:30:22,025 --> 00:30:27,185 at Columbia University, and then moved to Botswana and, and lived there for, 481 00:30:27,275 --> 00:30:32,345 for four years where I worked as a an HIV physician and you know, it was 482 00:30:32,345 --> 00:30:37,091 great, like on the one hand, I was able to, to see how care was delivered. 483 00:30:37,101 --> 00:30:41,976 I was providing HIV care in rural Botswana, but on the other hand, it 484 00:30:41,976 --> 00:30:47,886 was fairly jarring to be in a setting where, um, me as a UK trained, American 485 00:30:47,886 --> 00:30:52,716 paid physician was delivering care, while I was surrounded by people 486 00:30:52,726 --> 00:30:56,436 who were far better clinicians than me, but didn't have the resources. 487 00:30:56,796 --> 00:30:59,166 Um, and it really got me thinking about how do we improve the health 488 00:30:59,166 --> 00:31:02,666 systems in these countries so that they're able to respond to HIV. 489 00:31:03,086 --> 00:31:06,656 Um, so I did that for five years and, and realized actually I wanted to do more 490 00:31:06,656 --> 00:31:11,001 training and I was very interested in how do you optimize health systems in high 491 00:31:11,271 --> 00:31:15,471 HIV burden settings and then ended up doing fellowship after five years away. 492 00:31:15,921 --> 00:31:17,241 Um, did ID fellowship. 493 00:31:18,051 --> 00:31:21,081 By the time I'd finished ID fellowship, I was deep in the weeds on how 494 00:31:21,081 --> 00:31:22,641 do you optimize health systems? 495 00:31:22,641 --> 00:31:27,711 And, and that led to my subsequent career doing health policy 496 00:31:27,711 --> 00:31:29,481 research in the HIV space. 497 00:31:30,321 --> 00:31:34,591 Fast forward, uh, 10 years and, and now I work as the Chief 498 00:31:34,591 --> 00:31:35,851 Science Officer for PEPFAR. 499 00:31:35,901 --> 00:31:40,951 Really trying, trying to deliver on my own ambition to support 500 00:31:40,951 --> 00:31:42,781 and improve health systems, um, 501 00:31:43,016 --> 00:31:43,086 Yeah. 502 00:31:43,126 --> 00:31:44,356 in those countries. 503 00:31:44,846 --> 00:31:45,086 Yeah. 504 00:31:45,236 --> 00:31:50,106 I just wanted to open up to just a last question for you, Dr. Reid, anything 505 00:31:50,106 --> 00:31:54,756 that you can recommend for folks who are interested in global health in the 506 00:31:54,756 --> 00:31:59,206 future and folks who are interested in advocating for lenacapavir's 507 00:31:59,226 --> 00:32:01,326 implementation broadly going forward. 508 00:32:02,046 --> 00:32:03,246 Yeah, brilliant question. 509 00:32:03,246 --> 00:32:04,206 I love that question. 510 00:32:04,596 --> 00:32:08,096 So, let me zoom out and say I think global health is at an 511 00:32:08,096 --> 00:32:09,266 inflection point right now. 512 00:32:09,276 --> 00:32:14,750 We're at a point where there is a change of political priorities around 513 00:32:14,750 --> 00:32:16,160 the importance of global health. 514 00:32:16,560 --> 00:32:19,150 I think political attention is waning. 515 00:32:19,180 --> 00:32:25,760 And some of that moral ambition that led to PEPFAR being established is waning 516 00:32:26,250 --> 00:32:32,940 in places like the US and, and there is a really important responsibility 517 00:32:32,940 --> 00:32:40,180 on people that care about these issues to, to make a loud effective noise in 518 00:32:40,180 --> 00:32:42,640 support of initiatives like PEPFAR. 519 00:32:42,690 --> 00:32:45,660 PEPFAR has had an incredible impact over the last 20 years. 520 00:32:45,990 --> 00:32:50,940 Um, but to sustain that impact, I think does require an ongoing political 521 00:32:50,940 --> 00:32:52,650 investment from our leadership. 522 00:32:53,010 --> 00:32:57,820 And I, I think this is a, a really critical time for people interested in 523 00:32:57,820 --> 00:33:04,800 global health to exercise their advocacy and protesting capabilities to ensure 524 00:33:04,800 --> 00:33:09,500 that we continue to prioritize global health in settings like the US which 525 00:33:09,780 --> 00:33:13,165 historically has been the funder of substantial global health programming 526 00:33:13,215 --> 00:33:17,982 . And so I think there is a considerable value in, in folks like you Anshel 527 00:33:18,119 --> 00:33:21,796 telling your congresspeople and, and senators about the importance of PEPFAR. 528 00:33:22,406 --> 00:33:27,116 You know, as to the role of lenacapavir, again, there is no doubt that LEN is 529 00:33:27,206 --> 00:33:32,486 incredibly efficacious clinically, but but unless we're able to show that it's 530 00:33:32,486 --> 00:33:37,616 cost effective, then that that clinical efficacy won't be realized on the 531 00:33:37,616 --> 00:33:39,386 ground in the places that need it most. 532 00:33:40,091 --> 00:33:43,541 And in order for us to get to that point where it's cost effective, again, I 533 00:33:43,541 --> 00:33:49,411 think there is, there is real need for advocacy and ambition to ensure that we 534 00:33:49,411 --> 00:33:54,181 procure the volumes necessary in the first instance from Gilead to make it available. 535 00:33:54,671 --> 00:33:54,831 Mm. 536 00:33:54,831 --> 00:33:57,661 And that motivates the generics to, to, to invest. 537 00:33:57,661 --> 00:34:01,216 So the price comes down to a point at which partner governments can afford it. 538 00:34:02,891 --> 00:34:05,621 So for all of those reasons, I think there is a role for, for 539 00:34:05,621 --> 00:34:07,831 folks like you, advocating for LEN. 540 00:34:07,831 --> 00:34:08,911 I'll just say one last thing. 541 00:34:08,971 --> 00:34:12,091 Some of these things I write about on my substack, you can find 542 00:34:12,136 --> 00:34:12,376 Yeah. 543 00:34:12,481 --> 00:34:17,201 about my opinions on this and many other things at reimagineglobalhealth. 544 00:34:17,221 --> 00:34:18,121 substack.com. 545 00:34:21,911 --> 00:34:24,456 Thanks so much to Anshel and Mike for joining us today. 546 00:34:24,920 --> 00:34:28,880 You can find more info on our website, febrilepodcast.com, where 547 00:34:28,880 --> 00:34:32,074 we house the Consult Notes, which are written supplements of the 548 00:34:32,074 --> 00:34:36,154 episodes with links to references, our library of ID infographics, 549 00:34:36,154 --> 00:34:37,414 and a link to our merch store. 550 00:34:38,944 --> 00:34:42,694 Febrile is produced with support from the Infectious Diseases Society of America. 551 00:34:43,144 --> 00:34:45,904 Please reach out if you have any suggestions for future shows or 552 00:34:45,904 --> 00:34:47,434 wanna be more involved with Febrile. 553 00:34:47,507 --> 00:34:48,317 Thanks for listening. 554 00:34:48,557 --> 00:34:50,087 Stay safe and I'll see you next time.