乌鸦传媒

In a webcast at the 2020 virtual (CROI), , of Massachusetts General Hospital in Boston, presented new approaches to treating HIV, including agents with novel mechanisms of action; long-acting medications; and innovative delivery systems.

In this exclusive 乌鸦传媒 video, Gandhi discusses these current treatment options, as well as others on the horizon that have the potential to transform HIV management.

Following is a transcript of his remarks:

So, let me start out by just in broad strokes, talking about why do we need new antiretroviral therapy. Then we'll talk a little bit about the new drugs themselves, and then we'll try to synthesize it and put it all together in terms of how we're going to use these new drugs when they become available.

So why do we need new antiretroviral therapy? There are more than 30 approved antiretroviral drugs, and people are living longer and better with HIV than they ever have before. But, a couple of limitations still pertain to our current therapies. One is side effects. We know, even in recent years, there's been an increasing focus on weight gain and some other side effects that we didn't really grasp a few years ago. The other is drug interactions. Although our drugs are cleaner when it comes to drug interactions, they still do have drug interactions. Perhaps an even bigger limitation for some people living with HIV is that all our regimens today, every single one of them is a daily oral pill, or pills. And therefore people who have difficulty adhering to a daily oral medication have challenges. And then last but not least, there's the high cost of medications. And that's something that really needs to be grappled with as we move forward.

So what are the new drugs and how are we going to use them? So in terms of the new drugs, I'm going to start with those that are closest to the clinic and then move from there. And I'll start with new drugs that are using mechanisms that some of our current drugs already target. And the one I'll start with is long acting Cabotegravir and Rilpivirine. Cabotegravir of course is an integrase inhibitor. And Rilpivirine is a non-nucleoside RT inhibitor. At the CROI meeting this year, we saw new data on a long acting Cabotegravir/Rilpivirine, 96 week data from the FLAIR study. This showed us that the combination of a monthly Cabotegravir/Rilpivirine continue to look well as compared to oral daily antiretroviral therapy now out to 96 weeks. So that shows durability of this monthly intramuscular injection of Cabotegravir/Rilpivirine.

Even more exciting, I think is data from the ATLAS 2M study. This looked at a comparison of once monthly Cabotegravir/Rilpivirine to every two month injections. And the top line result from that is that the every two months looked as good as the every month. Remember of course that all these patients come into these trials already virologically suppressed. So that's an important point to be making about long acting therapy right now. It's for people who are suppressed. There will be practical considerations if this is approved. It's been approved in Canada, but not yet approved in the United States, in terms of how we deliver it, and that will be a really interesting discussion to have in the future in terms of how we deliver these drugs.

The next drug I'd like to turn to is a drug called Islatravir, this is a drug that is a nucleoside RT translocation inhibitor. This particular drug was studied in the drive to simplify study, which is a phase two B study in combination with doravirine, those results look promising. And so now Islatravir, this new class of drugs is being studied in phase 3 clinical trials that we're launching right around the time of CROI, in three important populations, treatment/naive people in the switch setting and people who are suppressed. And then in highly drug resistant populations.

What's intriguing about Islatravir is that it appears to have a very long half life. And so it may have applications with less frequent dosing. And also there's an implant that was reported on earlier at an earlier meeting, being designed for PrEP. And so those are other areas to keep your focus on for the future.

Capsid inhibitors is the next class of drugs, they've got prominence at CROI this year. Capsid inhibitors completely new mechanism, very long acting. It's a subcutaneous injection and it can last as much as six months. And so at this meeting, we saw some updated data on the antiviral effect of capsid inhibitors. And then we saw announcements that phase two studies are being launched, phase two phase three studies, with the capsid inhibitor in highly drug resistant populations, as well as treatment naive populations. And in some instances, being given as infrequently as every six months, although it's also combined with a more frequent dosing as in terms of its partner drugs.

And then the last two classes I'll talk about before synthesizing are entry inhibitors. We're aware of the entry inhibitors like Ibalizumab, which was approved in the past, Fostemsavir is moving forward. And two drugs that are further behind, UB-421 and Leronlimab. We also saw some information about these entry inhibitors. So something very much to keep your eye on for the future.

In my mind, these are going to be mostly used in highly drug resistant patients where they will have a really, at least Fostemsavir, could really have a lifesaving role in that particular population. That's very important. Nonetheless, before we synthesize our broadly neutralizing antibodies, these are getting a lot of interest, both for prevention, for cure, but also for treatment. And at this meeting, at the CROI meeting, we saw data suggesting that you can deliver these by vectors, by viral vectors that at least in principle could deliver the antibody over many, many months and really translate to a very long acting therapy.

So how are we going to use these drugs when, and if they come about. I think here we can take some lessons from other fields of medicine. We know that long acting contraception has really changed and given people more options when it comes to contraceptions. I think the lesson from long acting contraception is that choice matters. And having multiple options for different people is something we should aspire to in HIV. Bisphosphonates, some of them can be given once a year and those seem to be associated with better adherence than, um, more frequent dosing of bisphosphonates. So the lesson I take from that, this is for osteoporosis, is that the longer the better for many patients in terms of frequency of dosing. Long-acting psychiatric medications are also clinically used, but not widely. And one consideration there is, those are delivered often in facilities. So we're going to have to give some careful thought with long acting therapies as to where we deliver them. Can they be rolled out in a more user friendly patient friendly manner? And finally, the lesson of PCSK-9 inhibitors for cardiovascular disease. Those are not utilized as much as some people had thought they would be. And one of the considerations there is cost. And I think it brings back the fact that these long acting therapies, especially if we're going to use them broadly around the world, we need to make sure that there's both low cost as well as access.

And so that's how I would wrap up my discussion today. So a lot of exciting times still coming. I think the field of HIV remains dynamic and I think the new drugs are just one example of the dynamism in our field. Thank you very much for joining and hope to talk to you again.

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