1 00:00:06,096 --> 00:00:06,906 Hi everyone. 2 00:00:06,936 --> 00:00:11,286 Welcome to Febrile, a cultured podcast about all things infectious disease. 3 00:00:11,736 --> 00:00:15,666 We use consult questions to dive into ID clinical reasoning, diagnostics, 4 00:00:15,666 --> 00:00:17,256 and antimicrobial management. 5 00:00:18,006 --> 00:00:20,436 Thank you so much for your patience with getting some new 6 00:00:20,436 --> 00:00:22,056 episodes here on the podcast. 7 00:00:22,056 --> 00:00:25,342 I know there has been a little bit of a break as I try to keep up, but I have 8 00:00:25,342 --> 00:00:30,442 several episodes on their way to you and I'm super excited to share with you 9 00:00:30,472 --> 00:00:35,587 the most recent recording, which is live from ID week 2025 in Atlanta, Georgia. 10 00:00:36,194 --> 00:00:37,224 I am joined by Drs. 11 00:00:37,244 --> 00:00:41,301 Camille Kotton and Roy Chemaly to discuss a case and some of the challenges in 12 00:00:41,301 --> 00:00:46,491 diagnosis and management of refractory HSV infection in immunocompromised patients. 13 00:00:47,151 --> 00:00:52,004 This episode was recorded at IDWeek 2025 during one of the affiliated events. 14 00:00:52,214 --> 00:00:55,974 Our guests today and my role as moderator were sponsored speakers by AiCuris 15 00:00:55,994 --> 00:00:58,644 Anti-infective Cures for the event. 16 00:00:58,644 --> 00:01:03,014 However, this content was planned, produced, and reviewed solely by Febrile. 17 00:01:03,294 --> 00:01:03,954 Hope you enjoy. 18 00:01:04,806 --> 00:01:05,916 Hi everyone. 19 00:01:05,946 --> 00:01:08,416 Welcome to our session today. 20 00:01:08,786 --> 00:01:11,576 We are live from the ID Week Learning Lounge. 21 00:01:11,576 --> 00:01:12,956 Thank you for joining us. 22 00:01:13,326 --> 00:01:14,106 I'm Sara Dong. 23 00:01:14,106 --> 00:01:17,596 I'm your host and moderator today, and we have something special. 24 00:01:17,596 --> 00:01:22,126 This is actually going to be a Febrile podcast live recording here from IDWeek. 25 00:01:22,784 --> 00:01:26,294 And I hope some of you are already listeners, but if not, Febrile 26 00:01:26,294 --> 00:01:30,244 is a cultured podcast about all things infectious disease, and 27 00:01:30,244 --> 00:01:34,998 so I'm very excited to have two illustrious guest stars here with me. 28 00:01:35,308 --> 00:01:38,428 I'm gonna let them say hello and introduce themselves and we'll get started. 29 00:01:39,538 --> 00:01:40,078 Thank you. 30 00:01:40,318 --> 00:01:44,228 I'm Camille Nelson Cotton and I'm the Clinical Director of Transplant and 31 00:01:44,228 --> 00:01:48,138 Immunocompromised Host Infectious Diseases at Massachusetts General Hospital, and 32 00:01:48,138 --> 00:01:49,938 I'm really delighted to be with you today. 33 00:01:51,148 --> 00:01:52,088 I'm Roy Chemaly. 34 00:01:52,108 --> 00:01:56,578 I'm also Infectious Disease specialist, uh, Professor of Medicine and the Chair 35 00:01:56,938 --> 00:02:01,618 of the Infectious Disease department at MD Anderson Cancer Center in Houston, Texas. 36 00:02:01,618 --> 00:02:05,318 And I'm very happy to be surrounded by my colleagues here. 37 00:02:06,313 --> 00:02:07,423 Some rock stars here. 38 00:02:07,493 --> 00:02:11,753 Okay, so before we talk about a case today, I always ask one question on 39 00:02:11,753 --> 00:02:16,583 our podcast, uh, as everyone's favorite cultured podcast, if our guests can share 40 00:02:16,763 --> 00:02:20,063 a little piece of culture, basically just something non-medical that they enjoy. 41 00:02:20,423 --> 00:02:21,383 Uh, maybe I'll start with you, Roy. 42 00:02:21,383 --> 00:02:22,313 With me. 43 00:02:23,153 --> 00:02:23,303 Okay. 44 00:02:23,303 --> 00:02:23,323 Thank you. 45 00:02:23,543 --> 00:02:26,603 So I had to think a little about that, but really, you know, in my 46 00:02:26,603 --> 00:02:30,443 mind it's like really what give me not really happened, maybe serenity. 47 00:02:31,013 --> 00:02:34,343 And you're gonna be surprised like sipping coffee every morning. 48 00:02:34,763 --> 00:02:38,273 This is how I start my day and it's the best time of the day for me. 49 00:02:38,758 --> 00:02:39,438 I think so. 50 00:02:40,538 --> 00:02:42,618 So that is my culture moment. 51 00:02:42,988 --> 00:02:43,518 Love it. 52 00:02:44,393 --> 00:02:48,203 So I've had the good fortune of recently traveling to India where 53 00:02:48,203 --> 00:02:51,773 I went to the, um, heart and lung and abdominal transplant meetings 54 00:02:51,773 --> 00:02:56,693 and visited CMC Valore, um, medical school, and also went to Brazil. 55 00:02:56,693 --> 00:03:00,683 And I was so interested in just hearing about the culture of different 56 00:03:00,683 --> 00:03:02,393 transplant programs throughout the world. 57 00:03:02,393 --> 00:03:05,063 And I think there's just so much to learn from each other. 58 00:03:05,063 --> 00:03:10,223 So that's my somewhat, um, geeky but, uh, culture, um, for the day. 59 00:03:10,793 --> 00:03:11,393 Perfect. 60 00:03:11,903 --> 00:03:15,773 Okay guys, so, Roy and Camille are gonna help me out with a case today. 61 00:03:16,293 --> 00:03:19,473 I'm gonna get started and then pretty soon you'll see some pictures up on the screen. 62 00:03:20,103 --> 00:03:24,213 So we have a 65-year-old woman with acute myeloid leukemia who 63 00:03:24,213 --> 00:03:28,803 underwent a mismatched unrelated donor allogeneic stem cell transplant. 64 00:03:29,028 --> 00:03:33,078 She received fludarabine with busulfan conditioning and post- 65 00:03:33,198 --> 00:03:36,028 cyclophosphamide for GVHD prevention. 66 00:03:37,168 --> 00:03:41,578 Her course was complicated by acute upper gastrointestinal and skin GVHD, 67 00:03:41,788 --> 00:03:46,408 and so she began systemic steroid treatment about day+40 post-transplant. 68 00:03:47,368 --> 00:03:52,228 She was on HSV infection prophylaxis with valacyclovir dosed at one gram. 69 00:03:53,528 --> 00:03:57,468 She developed some ulcers, I'll show you some pictures here. 70 00:03:57,838 --> 00:04:03,898 She has some ulcers on her buccal mucosa, lips, nose, and then two on her 71 00:04:03,898 --> 00:04:07,688 tongue, which popped up around day 48. 72 00:04:08,048 --> 00:04:10,058 So you can see some examples here. 73 00:04:10,988 --> 00:04:14,828 Given these new lesions and concern for malabsorption, she 74 00:04:14,828 --> 00:04:20,408 was changed to IV acyclovir 10 mg/kg dosed three times daily. 75 00:04:21,178 --> 00:04:25,208 HSV PCR was sent from a lesion and confirmed to be HSV. 76 00:04:26,708 --> 00:04:30,098 She didn't really improve over the next week to week and a half. 77 00:04:30,098 --> 00:04:33,488 So at this point has been transitioned to IV foscarnet therapy. 78 00:04:34,238 --> 00:04:37,298 So I have to ask our experts, what do you guys think? 79 00:04:37,298 --> 00:04:39,548 Is this refractory HSV infection? 80 00:04:39,548 --> 00:04:41,948 Uh, maybe I can get started. 81 00:04:41,948 --> 00:04:47,068 So, yeah, defining refractory is very important and for years, uh, we 82 00:04:47,068 --> 00:04:51,878 didn't have any kind of standardized definition for refractory HSV infection. 83 00:04:52,178 --> 00:04:54,638 We, we developed one for CMV, but not for HSV. 84 00:04:54,878 --> 00:04:59,128 From the transplant associated viral infection forum, work with Camille and 85 00:04:59,128 --> 00:05:04,668 other expert, to define for clinical trial use, what we, uh, put there is 86 00:05:04,668 --> 00:05:12,138 someone with mucocutaneous lesions not improving or having new lesions after at 87 00:05:12,138 --> 00:05:15,738 least seven days of good anti HSV therapy. 88 00:05:16,248 --> 00:05:19,923 Uh, making sure the right route and the right dosage, uh, as well. 89 00:05:20,073 --> 00:05:25,233 And this is meant for clinical trials, but also it can be used at the bedside 90 00:05:25,233 --> 00:05:27,493 when it come to refractory infection. 91 00:05:28,059 --> 00:05:31,389 Definitely it's really important to make the diagnosis of refractory 92 00:05:31,389 --> 00:05:34,359 disease and then think about sending resistance testing. 93 00:05:34,629 --> 00:05:37,559 Resistance testing can take numerous weeks to return. 94 00:05:37,559 --> 00:05:42,269 So while we're waiting, we manage this as a refractory disease similar 95 00:05:42,269 --> 00:05:45,659 to how we manage, you know, how we think about CMV, but this is sort of 96 00:05:45,659 --> 00:05:48,959 a, a different, especially because they're much longer wait times in 97 00:05:49,019 --> 00:05:50,609 getting the resistance testing back. 98 00:05:51,299 --> 00:05:51,419 Yeah. 99 00:05:51,959 --> 00:05:54,569 So do you guys see this outside of stem cell transplant? 100 00:05:55,053 --> 00:05:56,823 Uh, yeah, absolutely. 101 00:05:56,823 --> 00:06:01,483 First I wanna say that it's not uncommon, this kind of scenario that 102 00:06:01,483 --> 00:06:05,548 you presented, especially someone who becoming heavily immunocompromised, 103 00:06:05,578 --> 00:06:10,078 immunosuppressed early on after transplant or even after induction chemo 104 00:06:10,078 --> 00:06:14,518 for leukemia patient, lymphoma patient on multiple line of therapy, myeloma. 105 00:06:14,518 --> 00:06:19,558 I can go on and on outside of transplant where you may encounter this 106 00:06:19,558 --> 00:06:24,118 kind of refractory and or resistant herpes simplex (HSV) infections. 107 00:06:24,808 --> 00:06:29,488 And we do see it sometimes in people with HIV and then we see it in the solid organ 108 00:06:29,488 --> 00:06:31,648 and other immunocompromised populations. 109 00:06:31,918 --> 00:06:35,098 It's fairly rare, but when it happens, it can be quite devastating. 110 00:06:35,098 --> 00:06:37,948 So it's really important to recognize the clinical syndrome. 111 00:06:39,118 --> 00:06:42,358 Yeah, and we have some pictures up here just listing out some of 112 00:06:42,358 --> 00:06:46,048 these risk factors that we think about for refractory HSV infection. 113 00:06:46,708 --> 00:06:49,768 And so, you know, at this point I mentioned that our patient has been 114 00:06:49,768 --> 00:06:53,908 on IV foscarnet therapy, which I'm sure many people in the audience have 115 00:06:54,703 --> 00:06:58,633 struggled with, I will say, um, you know, is this what we're stuck with? 116 00:06:58,633 --> 00:07:00,523 IV foscarnet and all its limitations? 117 00:07:00,523 --> 00:07:02,473 Are there other options available to us? 118 00:07:02,983 --> 00:07:07,723 So I would say unfortunately we are stuck with foscarnet alternative 119 00:07:07,723 --> 00:07:10,423 therapy, uh, for this kind of infection. 120 00:07:10,843 --> 00:07:14,983 Although having lots of experience foscarnet where we had to use it on many 121 00:07:14,983 --> 00:07:20,143 occasion for CMV infection or for herpes simplex, we know it is an effective drug, 122 00:07:20,143 --> 00:07:25,303 but it become affected when it goes at high incidence of serious toxicities. 123 00:07:25,483 --> 00:07:29,263 We are all familiar with nephro toxicities from foscarnet as 124 00:07:29,263 --> 00:07:32,863 well as electrolyte imbalance and many other toxicities as well. 125 00:07:33,974 --> 00:07:38,139 And in addition to foscarnet, in very specific cases, we sometimes 126 00:07:38,139 --> 00:07:42,049 can use topical antiviral therapy, topical cidofovir. 127 00:07:42,499 --> 00:07:46,879 Um, interestingly, we need to have that compounded and often the compounding 128 00:07:46,879 --> 00:07:51,544 agent, not the drug itself, but the compounding agent can be quite expensive 129 00:07:51,544 --> 00:07:54,034 and it's often not covered by insurance. 130 00:07:54,034 --> 00:07:59,734 So I've had prices in the range of $1500, $2,000 just for some 131 00:07:59,734 --> 00:08:01,504 basically topical therapies. 132 00:08:01,504 --> 00:08:05,944 So, um, sometimes it seems like a good choice, but can be very 133 00:08:05,944 --> 00:08:09,854 challenging to either obtain and or get covered by insurance. 134 00:08:09,854 --> 00:08:12,449 And, and I want to add to that beyond caution the audience, 135 00:08:12,779 --> 00:08:17,039 sometimes we have big lesions and you use topical, uh, cidofovir? 136 00:08:17,429 --> 00:08:18,749 Uh, it has to be compounded. 137 00:08:18,749 --> 00:08:21,569 Wanna make sure that it's compounded the right way, but it can still cause 138 00:08:21,569 --> 00:08:23,609 some side effect, can get absorbed. 139 00:08:23,609 --> 00:08:26,969 We had few cases, not many, only maybe one or two. 140 00:08:27,269 --> 00:08:31,529 Uh, and we publish on one when they develop renal toxicity from topical 141 00:08:31,584 --> 00:08:35,899 cidofovir, versus Fanconi syndrome and other kind of side effect that you have to 142 00:08:35,899 --> 00:08:38,249 be aware of as well when you use topical. 143 00:08:38,274 --> 00:08:40,944 It's a really good point, especially because these lesions can be 144 00:08:40,944 --> 00:08:44,814 fairly big and the skin is open, so at higher rates of absorption. 145 00:08:45,114 --> 00:08:47,754 And then we put it on often, multiple times a day. 146 00:08:47,754 --> 00:08:50,514 And so that's a, that's a really important thing to consider. 147 00:08:50,814 --> 00:08:54,684 The toxicity of all of these therapies is significant, so 148 00:08:54,684 --> 00:08:56,124 that's always a concern for us. 149 00:08:57,163 --> 00:09:00,993 So for this patient, I mentioned we're not really making progress, 150 00:09:00,993 --> 00:09:02,643 we don't have clinical improvement. 151 00:09:03,153 --> 00:09:06,213 What are your next steps at this point for evaluating this 152 00:09:06,213 --> 00:09:08,013 patient for, for treating them? 153 00:09:08,699 --> 00:09:12,539 So when we're thinking about refractory disease and we're 154 00:09:12,544 --> 00:09:14,394 switching to different therapies? 155 00:09:14,454 --> 00:09:15,024 Um, yeah. 156 00:09:15,024 --> 00:09:17,844 As you can see in this algorithm here, right? 157 00:09:18,399 --> 00:09:23,009 Usually we first of all recognize the refractory HSV infection 158 00:09:23,009 --> 00:09:27,929 risk, and then often switch to intravenous foscarnet therapy. 159 00:09:27,929 --> 00:09:31,949 I always ask my pharmacist for help, and I personally always keep people in 160 00:09:31,949 --> 00:09:33,579 the hospital when they're on foscarnet. 161 00:09:33,599 --> 00:09:35,369 I don't send them home, I don't think it's safe. 162 00:09:36,029 --> 00:09:40,199 And then really importantly, early send resistance testing because, 163 00:09:40,259 --> 00:09:43,529 uh, it can take quite a while for the resistance testing to come back 164 00:09:43,529 --> 00:09:45,359 sometimes a month or even longer. 165 00:09:45,359 --> 00:09:46,619 It can really be problematic. 166 00:09:47,504 --> 00:09:49,784 And then once you had the resistance results, you know, you 167 00:09:49,784 --> 00:09:51,314 can see as marching through this. 168 00:09:51,314 --> 00:09:55,874 If it is still acyclovir susceptible, foscarnet susceptible, then it 169 00:09:55,874 --> 00:09:59,234 should work to try them on either intravenous acyclovir or high dose 170 00:09:59,264 --> 00:10:05,274 valacyclovir, or potentially consider, uh, investigational therapies. 171 00:10:05,324 --> 00:10:09,404 And that's where we think about things like pritelivir, 172 00:10:09,474 --> 00:10:10,464 when it's available. 173 00:10:10,464 --> 00:10:14,214 Obviously if it's acyclovir resistance, then we probably want something like 174 00:10:14,214 --> 00:10:19,224 foscarnet or investigational therapy, or if it's acyclovir susceptible, as 175 00:10:19,224 --> 00:10:22,734 you can see on the right hand side of the slide, and foscarnet resistant, 176 00:10:22,734 --> 00:10:27,114 go, go with, potentially intravenous cidofovir, which, many of us are not 177 00:10:27,114 --> 00:10:31,224 really using significantly and it could be quite challenging to get or 178 00:10:31,224 --> 00:10:32,904 potential investigational therapy. 179 00:10:33,369 --> 00:10:36,579 And probably I would add that's also the main thing when we develop 180 00:10:36,579 --> 00:10:40,119 this algorithm, you know, want to give alternative therapy, right? 181 00:10:40,119 --> 00:10:45,009 But also wanna make sure that providers recognize refractory early on. 182 00:10:45,369 --> 00:10:49,299 And because I know in the old days when we are faced with this kind of, uh, 183 00:10:49,329 --> 00:10:54,519 patient with all this non well, we keep on pushing with foscarnet or even high dose 184 00:10:54,519 --> 00:10:58,659 acyclovir and we don't know what to do, but recognizing the refractory early on 185 00:10:58,659 --> 00:11:04,939 and maybe switching therapy based on geno topic testing, it could improve outcome. 186 00:11:05,149 --> 00:11:10,189 But we realize big unmet need when we have alternative therapy, very toxic drug. 187 00:11:10,429 --> 00:11:16,079 We need a new drug that are safer and effective in treating this kind of, 188 00:11:16,079 --> 00:11:18,239 uh, scenarios, this kind of infection. 189 00:11:18,239 --> 00:11:22,529 That's why, you know, at least hopefully, you all probably heard about the 190 00:11:22,529 --> 00:11:24,029 press release that we're gonna have. 191 00:11:24,359 --> 00:11:28,509 Uh, you know, the primary endpoint was met for pritelivir and mucocutaneous 192 00:11:28,529 --> 00:11:31,259 HSV resistant refractory infection. 193 00:11:31,259 --> 00:11:36,629 So hope is on the horizon, I would say, to have kind of oral and safer 194 00:11:36,689 --> 00:11:38,669 drug to treat this kind of infection. 195 00:11:38,969 --> 00:11:41,534 So stay tuned, more to come in the future. 196 00:11:41,954 --> 00:11:42,174 So. 197 00:11:42,514 --> 00:11:47,879 And I would also also include any good transplant infectious disease note always 198 00:11:47,879 --> 00:11:52,619 contains the line, please try to reduce immunosuppression as much as possible. 199 00:11:52,619 --> 00:11:55,979 Um, which is easier said than done. 200 00:11:55,979 --> 00:12:01,169 And I think a lot of the patients that I have seen with resistant HSV are quite 201 00:12:01,169 --> 00:12:05,489 immunocompromised and not necessarily by exogenous immunosuppression, but 202 00:12:05,759 --> 00:12:07,619 stem cell transplant or whatnot. 203 00:12:07,619 --> 00:12:11,039 So it's always easier said than done to reduce the immunosuppression, but 204 00:12:11,039 --> 00:12:13,229 that's always part of the algorithm. 205 00:12:13,529 --> 00:12:16,894 And thanks for highlighting the phase three data. 206 00:12:16,894 --> 00:12:20,044 I will be talking about the phase two data later this afternoon. 207 00:12:20,434 --> 00:12:26,744 I'll be speaking at 3:51 PM and it will be in room, uh, B 213-214. 208 00:12:27,364 --> 00:12:30,264 Um, so if you're interested in hearing the earlier phase two 209 00:12:30,264 --> 00:12:32,214 data, um, it will be presented. 210 00:12:33,084 --> 00:12:33,624 Perfect. 211 00:12:33,954 --> 00:12:34,194 Okay. 212 00:12:34,194 --> 00:12:36,534 Well, tell us a little bit about our patient. 213 00:12:36,884 --> 00:12:41,084 Unfortunately, our patient had to stop foscarnet prior to healing 214 00:12:41,084 --> 00:12:44,264 of lesions due to renal toxicity. 215 00:12:44,604 --> 00:12:50,304 The patient received imiquimod 5% cream and did also have the cidofovir 1% 216 00:12:50,394 --> 00:12:52,824 oral solution as adjuvant treatments. 217 00:12:53,154 --> 00:12:57,024 Um, but this patient ultimately received compassionate use pritelivir, 218 00:12:57,454 --> 00:13:01,564 and actually had complete response after about 40 days of therapy. 219 00:13:02,204 --> 00:13:05,114 Is there anything else that you guys can share with us, with, you 220 00:13:05,114 --> 00:13:06,464 know, experience in cases like this? 221 00:13:07,019 --> 00:13:12,229 Yeah, actually this is one of the case that we published in the CMI recently, 222 00:13:12,499 --> 00:13:17,659 one of our fellows, Tali Shafat, put this picture together and, uh, interesting. 223 00:13:17,659 --> 00:13:20,989 As you all know, probably, uh, phase two and phase three open label. 224 00:13:21,229 --> 00:13:24,649 So we could tell what patient is getting and this what we follow 225 00:13:24,649 --> 00:13:27,379 progression and, and our experience. 226 00:13:27,379 --> 00:13:31,994 We enroll many patient either on the phase two, phase three trial or, under 227 00:13:31,994 --> 00:13:37,784 the Compassionate use Program and our experience, uh, with many patient 228 00:13:38,024 --> 00:13:43,044 that you see the improvement rather quickly after you switch to pritelivir. 229 00:13:43,394 --> 00:13:47,084 And we documented this in pictures, uh, based on the protocol and based 230 00:13:47,084 --> 00:13:49,064 on what we've seeing clinically. 231 00:13:49,334 --> 00:13:53,354 So, yeah, that's why it is an interesting, effective drug we could tell. 232 00:13:53,534 --> 00:13:57,254 So it was not surprising when we saw the press release that it met the 233 00:13:57,254 --> 00:14:00,569 primary endpoint because we could see it firsthand, patient responding. 234 00:14:00,779 --> 00:14:03,809 And this patient, you know, need to keep in mind patient who get these 235 00:14:03,809 --> 00:14:06,779 kind of infections with no improvement. 236 00:14:06,959 --> 00:14:07,949 They're very complicated. 237 00:14:07,949 --> 00:14:10,589 You know, this patient had many other complications. 238 00:14:10,679 --> 00:14:14,339 This was a heavily immunocompromised, they have other type of infection at the 239 00:14:14,339 --> 00:14:20,739 same time, and you expose them to toxic drug, make their outcome probably worse. 240 00:14:20,979 --> 00:14:24,369 And we're talking about ultimate outcome sometimes, uh, either 241 00:14:24,369 --> 00:14:26,439 oncology outcome or mortality. 242 00:14:26,709 --> 00:14:32,254 So having a drug, which is oral drug, but it's effective and safer for a drug. 243 00:14:32,254 --> 00:14:36,904 And seeing, uh, the improvement and the impact on this kind of 244 00:14:36,904 --> 00:14:40,784 infection, actually, it is important for a significant, at least we 245 00:14:40,784 --> 00:14:45,379 accomplish something, uh, for our patient with new antiviral and. 246 00:14:45,384 --> 00:14:49,099 And al also to address, in addition to what we see clinically, but 247 00:14:49,104 --> 00:14:50,774 the patient experience, right? 248 00:14:51,104 --> 00:14:56,699 So this is incredibly painful and people are often really suffering. 249 00:14:56,759 --> 00:15:00,299 It can be at multiple sites and certainly when they're on 250 00:15:00,299 --> 00:15:02,279 foscarnet, that is not easy. 251 00:15:02,279 --> 00:15:07,139 And this is often in the setting of recent stem cell transplant or other therapies. 252 00:15:07,139 --> 00:15:12,269 So they're going through a lot and I really respect the patient experience 253 00:15:12,269 --> 00:15:18,009 and how therapies that are much easier, like oral therapy are easier for them 254 00:15:18,009 --> 00:15:19,779 with, uh, far fewer side effects. 255 00:15:20,434 --> 00:15:22,954 It's really wonderful to offer them something with less 256 00:15:22,954 --> 00:15:25,264 toxicity and fewer complications. 257 00:15:25,821 --> 00:15:29,871 You've already sort of started listing your wishlist of what you would want, 258 00:15:29,871 --> 00:15:34,501 but what do you see on the horizon for helping us with refractory HSV? 259 00:15:34,501 --> 00:15:36,061 What do you hope for? 260 00:15:36,061 --> 00:15:39,271 I feel like that'll be a nice place to end on, and then we'll see if 261 00:15:39,271 --> 00:15:40,141 the audience has any questions. 262 00:15:41,761 --> 00:15:44,311 Uh, so we talked about the HPI inhibitors. 263 00:15:45,031 --> 00:15:49,931 So, one of the HPI inhibitor, which is pritelivir, is helicase primase inhibitor 264 00:15:49,931 --> 00:15:51,851 has specific mechanisms of actions. 265 00:15:52,201 --> 00:15:56,581 There's no gross resistance, and this is important to know between HPIs 266 00:15:56,871 --> 00:15:59,961 versus acyclovir, uh, or even foscarnet. 267 00:16:00,351 --> 00:16:03,681 So this is important when you are suspecting resistant to either of the 268 00:16:03,681 --> 00:16:09,121 commercially available drug, at least from your field, you know that it, 269 00:16:09,121 --> 00:16:13,091 if it's gonna work, gonna work with no worrying about cross resistance. 270 00:16:13,361 --> 00:16:17,411 I always tell, uh, this drug that, you know, we've been working in the antiviral 271 00:16:17,411 --> 00:16:22,271 field for the past 20 years, myself and Camille, and we want to really bring 272 00:16:22,541 --> 00:16:26,951 new strategies and new agent to the market in a way to help our patient. 273 00:16:26,951 --> 00:16:28,001 And this is so important. 274 00:16:28,436 --> 00:16:32,606 And, you know, and we were successful so far for CMV and now 275 00:16:32,606 --> 00:16:36,556 we feel great about having a new antiviral, which is pritelivir. 276 00:16:36,806 --> 00:16:40,676 Hopefully, hopefully, it met the primary endpoint, we see by next year coming 277 00:16:40,676 --> 00:16:42,311 to the market to help our patient. 278 00:16:42,311 --> 00:16:46,716 At the end, it's really about our patient going through transplant, going 279 00:16:46,716 --> 00:16:51,486 through cancer therapy, solid organ transplant, and we wanna really help 280 00:16:51,486 --> 00:16:56,536 them to go through their journey in the best way possible, preventing infection, 281 00:16:56,596 --> 00:17:01,396 treating infection, keep them alive to recover from their underlying disease. 282 00:17:01,576 --> 00:17:02,626 And this is our hope. 283 00:17:03,016 --> 00:17:06,091 Hopefully we get there before we retire. 284 00:17:07,051 --> 00:17:11,491 With all of the amazing cancer therapies, biologic therapies for 285 00:17:11,491 --> 00:17:13,861 autoimmune disease, organ transplant. 286 00:17:14,281 --> 00:17:18,391 It's wonderful when infection can really take a back seat and have, you 287 00:17:18,391 --> 00:17:24,301 know, treatment and prevention can have minimal toxicity, minimal side effects, 288 00:17:24,301 --> 00:17:26,971 and sort of not be first and foremost. 289 00:17:26,971 --> 00:17:31,271 Unfortunately, many of the patients that I've cared for with refractory resistant 290 00:17:31,271 --> 00:17:36,851 HSV, have really had the HSV be their most significant issue at that point. 291 00:17:36,851 --> 00:17:41,111 So it would be great if it could be well treated and, um, yeah, take a 292 00:17:41,111 --> 00:17:44,891 backseat and hopefully enhance the quality of life and overall outcomes 293 00:17:44,891 --> 00:17:46,706 for this vulnerable population. 294 00:17:47,076 --> 00:17:50,891 I add one quick thing as well, that, you know, Camille mentioned a little bit. 295 00:17:51,461 --> 00:17:57,411 Now with the major advancement in treating hematologic malignancies in 296 00:17:57,411 --> 00:18:01,231 transplant, in cellular therapy, and probably in solid organ transplant, 297 00:18:01,581 --> 00:18:02,961 we gonna see more and more. 298 00:18:02,961 --> 00:18:07,071 We are gonna be faced with more challenging infectious complications 299 00:18:07,371 --> 00:18:11,991 because our patients are living longer, but they are more immunosuppressed, 300 00:18:12,306 --> 00:18:17,416 going through multiple line of therapy to get to the last strategy, the new 301 00:18:17,716 --> 00:18:20,466 innovations and, uh, new strategies. 302 00:18:20,496 --> 00:18:24,486 So we are start to see high acuity and severity of infection when 303 00:18:24,486 --> 00:18:28,776 patient get admitted, including viral infections, uh, you know, from 304 00:18:28,776 --> 00:18:30,306 CMV to herpes simplex and other. 305 00:18:30,516 --> 00:18:33,311 So is this gonna, unfortunately gonna stay with us. 306 00:18:33,561 --> 00:18:36,366 We're not gonna get rid of it, but we need to work hard. 307 00:18:36,576 --> 00:18:42,351 How to prevent it better, or how to add better treatment option to these patients. 308 00:18:42,881 --> 00:18:44,191 You're definitely right. 309 00:18:44,191 --> 00:18:48,921 In the past decade, there was a survey by the CDC and we've actually doubled 310 00:18:48,921 --> 00:18:53,001 the number of people in the United States who identify as immunocompromised. 311 00:18:53,001 --> 00:18:56,611 Now it's at 6.6% identify as immunocompromised. 312 00:18:56,611 --> 00:19:00,631 So we've made a lot of progress and we've certainly seen that, 313 00:19:00,631 --> 00:19:03,391 but we need to make sure that we have really good preventative and 314 00:19:03,391 --> 00:19:07,501 therapeutic options for, um, infectious disease in that, in that setting. 315 00:19:07,801 --> 00:19:10,201 We are really excited for the future ahead. 316 00:19:10,201 --> 00:19:15,341 I heard at ID week about an HSV vaccine even that might be on the horizon. 317 00:19:15,341 --> 00:19:19,461 So hopefully there'll be multiple modalities and, lots of ways 318 00:19:19,461 --> 00:19:20,871 that we can help patients. 319 00:19:21,424 --> 00:19:25,744 Well, we left a little time so that if folks in the audience had questions 320 00:19:25,744 --> 00:19:31,354 for our guests, uh, you may just, if you shout out to me and I'll repeat it 321 00:19:31,444 --> 00:19:34,324 or, um, you can walk up to the front. 322 00:19:34,534 --> 00:19:36,514 Oh, we can hand a mic if we need to. 323 00:19:37,084 --> 00:19:38,614 Any questions that folks have? 324 00:19:40,020 --> 00:19:41,065 Thank you so much. 325 00:19:41,125 --> 00:19:43,345 We come from Florida, Miami. 326 00:19:43,405 --> 00:19:44,035 Um, thank you. 327 00:19:44,275 --> 00:19:47,035 Um, my question is about the cidofovir. 328 00:19:47,035 --> 00:19:49,285 How do you mix it and how you apply it? 329 00:19:50,344 --> 00:19:53,554 Cidofovir needs to be compounded, so you need to have a compounding 330 00:19:53,554 --> 00:19:57,004 pharmacy, or, my inpatient pharmacy had previously done that. 331 00:19:57,579 --> 00:19:59,199 But it's actually really challenging. 332 00:19:59,199 --> 00:20:01,089 At least it's been in my clinical experience. 333 00:20:01,089 --> 00:20:04,479 I don't know what yours has been, but it's actually really hard to get compounding 334 00:20:04,479 --> 00:20:06,759 done and then covered by insurance. 335 00:20:07,239 --> 00:20:11,409 And it's, it seems shockingly challenging, like a couple thousand 336 00:20:11,409 --> 00:20:13,969 dollars to get a relatively small amount. 337 00:20:14,209 --> 00:20:17,484 Our pharmacists were always yelling at me saying, use very little and 338 00:20:17,484 --> 00:20:21,419 don't wipe it off, because it's actually sort of liquid gold. 339 00:20:21,749 --> 00:20:25,974 But there are some compounding pharmacies that can take care of that for you. 340 00:20:26,024 --> 00:20:26,384 Yeah. 341 00:20:26,384 --> 00:20:28,154 And, uh, I wanna add also. 342 00:20:28,154 --> 00:20:29,174 Yeah, I totally agree. 343 00:20:29,174 --> 00:20:33,074 And you have to make sure you get the right concentration because, 344 00:20:33,074 --> 00:20:36,764 I remember one patient mess up, give them higher concentration and 345 00:20:36,764 --> 00:20:38,599 they got into trouble with that. 346 00:20:38,979 --> 00:20:43,304 Uh, but also the, the, all of the question is, does it work? 347 00:20:43,844 --> 00:20:44,804 We don't know, right? 348 00:20:44,834 --> 00:20:47,064 So topical cidofovir or imiquimod. 349 00:20:47,399 --> 00:20:50,189 We use it because we have no other alternative. 350 00:20:50,249 --> 00:20:53,519 We wanna do whatever it takes for our patient and we try that. 351 00:20:53,519 --> 00:20:55,139 But I dunno, I'm not sure. 352 00:20:55,499 --> 00:20:59,549 Because we always use it in combination with other drugs as well, with all 353 00:20:59,549 --> 00:21:01,049 the other drugs that available. 354 00:21:01,049 --> 00:21:04,809 So something you have to keep in mind as well.\ 355 00:21:05,619 --> 00:21:06,609 Hi, uh, here. 356 00:21:06,609 --> 00:21:08,709 I'm Nadine from Milwaukee, Wisconsin. 357 00:21:09,284 --> 00:21:15,734 Question about a patient who would been on Valtrex suppression for genital HSV now 358 00:21:15,734 --> 00:21:18,644 suddenly starts having multiple outbreaks. 359 00:21:18,884 --> 00:21:20,684 The management of this patient. 360 00:21:20,744 --> 00:21:25,334 Is it, are you thinking this is now getting into a resistance zone? 361 00:21:25,394 --> 00:21:28,814 Or what should we do next and what are the treatment options for someone like that? 362 00:21:29,091 --> 00:21:34,201 So yeah, so the question is about having, uh, outbreak of herpes simplex 363 00:21:34,221 --> 00:21:36,681 on multiple occasions and what to do. 364 00:21:37,071 --> 00:21:37,491 So, yeah. 365 00:21:37,491 --> 00:21:40,551 And when we see this quite often, unfortunately, I had one 366 00:21:40,551 --> 00:21:41,901 patient following in the clinic. 367 00:21:42,231 --> 00:21:43,851 She come every month. 368 00:21:44,001 --> 00:21:45,411 It's like unbelievable. 369 00:21:45,411 --> 00:21:48,861 Like at the same time of the month where she has an outbreak. 370 00:21:49,071 --> 00:21:52,491 So what I did initially, you know, you put her on prophylaxis again, 371 00:21:52,821 --> 00:21:56,691 and you test for, uh, resistance, no resistance, refractory. 372 00:21:56,691 --> 00:21:59,211 That's the underlying cyclic neutropenia. 373 00:21:59,211 --> 00:22:02,256 That's why she get them when, but even on suppressive therapy, 374 00:22:02,256 --> 00:22:03,426 sometimes it doesn't work. 375 00:22:03,816 --> 00:22:08,226 So what I did, I increased the dose of, it's not really prophylaxis anymore, 376 00:22:08,586 --> 00:22:10,086 you know, it's not like one gram a day. 377 00:22:10,086 --> 00:22:15,036 I put them first on one gram twice a day, and then three times a day because 378 00:22:15,036 --> 00:22:19,836 it was a recurring outbreak every month, and it's still happening, unfortunately 379 00:22:20,076 --> 00:22:23,556 now, the last time it happened, because she did not take the prophylaxis. 380 00:22:23,571 --> 00:22:28,071 So, you know, I had to, you know, but, but, you know, but it, it's, uh, sometime 381 00:22:28,071 --> 00:22:35,401 it is hard, uh, you don't know what to do, except increasing the dose of acyclovir. 382 00:22:36,231 --> 00:22:37,791 Yeah, I, I completely agree. 383 00:22:37,791 --> 00:22:41,661 Um, it's just that sometimes you will have full resistance and then 384 00:22:41,661 --> 00:22:43,951 we need a better preventative option. 385 00:22:43,951 --> 00:22:47,341 And I don't think most of us would be giving like cidofovir every 386 00:22:47,341 --> 00:22:49,561 two weeks as was done for CMV. 387 00:22:49,561 --> 00:22:51,616 I mean, that's really toxic. 388 00:22:51,676 --> 00:22:57,916 Um, so that's really, uh, a huge unmet need is the ongoing prophylaxis situation 389 00:22:57,916 --> 00:22:59,416 for somebody who really needs it. 390 00:22:59,866 --> 00:23:02,956 I will say on a stewardship front, I usually try to stop the 391 00:23:02,956 --> 00:23:05,446 acyclovir as soon as it seems safe. 392 00:23:05,446 --> 00:23:09,226 I do find some people who are on acyclovir for a very long period 393 00:23:09,226 --> 00:23:13,966 of time, so I do try to stop and hopefully, hopefully decrease the risk 394 00:23:13,966 --> 00:23:18,086 of resistance, although, we don't really know about whether it's better to be on 395 00:23:18,086 --> 00:23:20,516 prophylaxis versus stop and then treat. 396 00:23:20,516 --> 00:23:23,396 We often think that when we're treating, it might be a trigger, 397 00:23:23,396 --> 00:23:26,726 at least for CMV, at a higher risk for developing resistance. 398 00:23:27,266 --> 00:23:31,436 Um, but it's a, a problematic situation, but we're cautiously optimistic 399 00:23:31,436 --> 00:23:35,156 that on the horizon there'll be, you know, options for both treatment of 400 00:23:35,156 --> 00:23:39,116 resistant disease and potentially prophylaxis of resistant disease. 401 00:23:39,116 --> 00:23:42,866 So it's a great, it's a great question and we're hopeful for the future. 402 00:23:44,289 --> 00:23:45,969 Any other questions? 403 00:23:50,479 --> 00:23:51,649 Well, I'll open it back up to you guys. 404 00:23:51,649 --> 00:23:53,449 I was gonna say for kind of some closing thoughts. 405 00:23:53,449 --> 00:23:53,509 Yeah. 406 00:23:53,869 --> 00:23:56,629 So maybe, uh, uh, closing thoughts. 407 00:23:56,719 --> 00:23:57,079 Yeah. 408 00:23:57,079 --> 00:23:57,319 Yeah. 409 00:23:57,319 --> 00:24:01,849 So yeah, so we, we, so we covered, uh, the main thing I would say from 410 00:24:01,849 --> 00:24:05,654 what we presented is make sure you use the definitions of refractory, 411 00:24:06,164 --> 00:24:11,384 although it meant only for clinical trial use, but I think it's helpful. 412 00:24:11,384 --> 00:24:15,054 I hear it from many people throughout the country, uh, from everywhere 413 00:24:15,054 --> 00:24:19,344 that it helped them at the bedside as well because, you know, we develop 414 00:24:19,344 --> 00:24:23,214 this definition based on our clinical experience because it's hard. 415 00:24:23,314 --> 00:24:25,534 If you look at the literature, it's all over the place. 416 00:24:25,534 --> 00:24:30,244 How people define refractory infections, uh, not only herpes simplex but 417 00:24:30,244 --> 00:24:31,984 maybe other viral infection as well. 418 00:24:32,194 --> 00:24:36,124 So at least we have something more standardized, can help us at the bedside. 419 00:24:36,604 --> 00:24:41,074 This way we can realize, or we can recognize refractory early on, we 420 00:24:41,074 --> 00:24:46,774 always good to switch therapy early on than later on when it is progressing 421 00:24:46,984 --> 00:24:51,214 or disseminating or having new lesions would be harder, uh, to treat. 422 00:24:51,664 --> 00:24:53,224 And, you know, so we talked about that. 423 00:24:53,224 --> 00:24:57,589 And now we talked also about the, hopefully a new HPI or 424 00:24:57,594 --> 00:25:00,569 helicase primase inhibitor coming to the market with pritelivir. 425 00:25:00,589 --> 00:25:05,599 Hopefully we are hoping next year, uh, now the data is under analysis 426 00:25:05,659 --> 00:25:09,809 and we're looking forward to see the data published in the future. 427 00:25:10,109 --> 00:25:11,099 Uh, this new strategy. 428 00:25:12,419 --> 00:25:15,489 Definitely it's a great time to be in transplant ID. 429 00:25:15,489 --> 00:25:20,969 We've had multiple new agents for CMV, you know, letermovir, which has been a game 430 00:25:20,969 --> 00:25:25,319 changer for prophylaxis and then maribavir for resistant refractory disease. 431 00:25:25,319 --> 00:25:28,589 And hopefully on the horizon we'll have new therapies for, 432 00:25:28,679 --> 00:25:30,579 uh, refractory resistant HSV. 433 00:25:30,599 --> 00:25:34,799 And we definitely welcome more tools in the toolbox. 434 00:25:36,119 --> 00:25:38,579 Well, I just wanna say thank you again for this. 435 00:25:38,939 --> 00:25:42,239 Um, for those of you who are here, we have some Febrile stickers in the 436 00:25:42,239 --> 00:25:44,099 front and a few minutes in the room. 437 00:25:44,099 --> 00:25:47,199 So if you do have questions, please feel free to come up, um, and say hello. 438 00:25:49,573 --> 00:25:51,043 Thanks again for listening, everyone. 439 00:25:51,043 --> 00:25:53,803 Happy to be back with you in action on Febrile. 440 00:25:54,133 --> 00:25:57,103 Don't forget to check out the website febrilepodcast.com, where 441 00:25:57,103 --> 00:25:59,863 you can find our Consult Notes, which are written complements to the 442 00:25:59,863 --> 00:26:03,913 episodes with links to references, our library of ID infographics, 443 00:26:03,943 --> 00:26:05,263 and a link to our merch store. 444 00:26:06,073 --> 00:26:08,503 Febrile is produced with support from the Infectious Diseases 445 00:26:08,503 --> 00:26:10,363 Society of America, IDSA. 446 00:26:10,903 --> 00:26:13,723 Please reach out if you have any suggestions for future shows or 447 00:26:13,723 --> 00:26:15,253 wanna be more involved with Febrile. 448 00:26:15,493 --> 00:26:16,303 Thanks for listening. 449 00:26:16,543 --> 00:26:18,043 Stay safe and let's see you next time. 450 00:26:18,073 --> 00:26:18,103 Okay.