New approaches to HIV prevention, care of HIV-positive patients

In this podcast, Charles Flexner, MD, talks about the current state of long-acting agents for the management of HIV patients, HIV prevention and vaccines, and the pathogenesis and cure of HIV. Dr. Flexner also participated in a panel discussion on these topics during Identification Week 2022 titled “HIV: State of the ART”.

This podcast was recorded before IDWeek 2022.

Additional resource:

  • Flexner C, Barouch D, Caskey M. HIV: state of the art. Conference presented at: IDWeek 2022; October 19-23, 2022; Washington DC. Accessed October 19, 2022.

Charles Flexner, MD, is Professor of International Health at the Bloomberg School of Public Health and Professor of Infectious Diseases and Clinical Pharmacology at Johns Hopkins University School of Medicine (Baltimore, MD).


TRANSCRIPTION:

Jessica Bard: Hello everyone and welcome to another episode of Podcast 360, your go-to resource for medical news and clinical updates. I’m your facilitator, Jessica Bard, at Consultant 360, a multidisciplinary medical information network. The World Health Organization has published additional guidelines for the use of pre-exposure prophylaxis for HIV. Dr. Charles Flexner is here to tell us today about a panel discussion he participated in during ID Week 2022 called HIV: State of the Art. Dr. Flexner is Professor of International Health at the Bloomberg School for Public Health and Professor of Infectious Diseases and Clinical Pharmacology at Johns Hopkins University School of Medicine in Baltimore, Maryland. Thank you for being with us today, Dr. Flexner. Could you please give us an overview of this discussion?

Doctor Charles Flexner: This symposium, which will take place on Thursday, is called HIV: State of the Art. And there will be three presentations in this session. One will be a presentation on the current state of long-acting agents for the treatment of HIV, and I will be moderating that session. There will be two other presentations during this session, one on HIV prevention and vaccines and the other on HIV pathogenesis and cure.

Jessica Bard: What do you think are the new strategies being prepared to find a cure for HIV?

Doctor Charles Flexner: Most of the strategies currently being followed try, if you will, to expel HIV from its latent reservoir and get the virus to start replicating so that it can be targeted by antiretroviral drugs and other drugs that eliminate cells that harbored HIV for very, very long periods of time. I must say that, at least until today, the only way to cure a patient infected with HIV was a bone marrow transplant. And that’s a pretty extreme intervention to try to eradicate HIV. But at least so far, that’s the only thing that has worked.

Some of these other approaches, the so-called kick-and-kill approach, which is kicking HIV out of its latent reservoir and then killing it with antiretrovirals and other drugs, I think there’s been a ray of hope in these studies, but so far nothing that has appeared to be able to reduce the latent reservoir of HIV to the extent necessary to attempt to obtain a sterilizing cure or a functional cure.

Jessica Bard: What do you think are the new biomedical approaches to HIV prevention?

Doctor Charles Flexner: At this symposium, we will hear about the use of broadly neutralizing anti-HIV monoclonal antibodies to prevent HIV infection. There was a very large study, the AMP study, sponsored by the HIV Prevention Trials Network, which was published in the New England Journal of Medicine last year. And this study used only one monoclonal antibody given monthly, but it appeared to prevent HIV infection in people in areas where the circulating virus was susceptible to the antibody, although the benefit overall of this antibody did not materialize.

So I think we learned a lot from this trial. One thing we’ve learned is that if we’re going to use broadly neutralizing monoclonal antibodies for prevention, we’re almost certainly going to have to use more than one, maybe three or four at a time, in order to cover all the virus that’s could circulate in an area where the person at risk lives. So it’s going to be a bit more complicated to develop these agents, but they now have terrific pharmacokinetic properties with long-acting modifications, allowing these antibodies to be delivered every three to six months. And it is pharmacologically possible to combine several antibodies in a single injection. So even though there would be three or maybe four antibodies involved, it would be invisible to the patient. They would receive a single injection or infusion of the antibody, whether it is one antibody or several.

Jessica Bard: Could you tell us more about the drugs that have also been approved for HIV prevention?

Doctor Charles Flexner: Yes. You’re talking about the long-acting cabotegravir, which was originally developed for the treatment of HIV. And it’s a drug that I’m going to talk about in my talk on long-acting formulations. Cabotegravir is an integrase inhibitor, closely related to dolutegravir, which is formulated for very slow release from intramuscular depot. And in HIV prevention studies sponsored by the National Institutes of Health, in prospective, randomized, double-blind, placebo-controlled studies, compared to standard of care, which is tenofovir disoproxil fumarate plus emtricitabine, Cabotegravir injection, given initially once a month, then once every two months, every eight weeks, was significantly more effective in preventing new HIV infections in MSM and transgender women in the HPTN 083 study, and in cisgender women in the HPTN study, HIV Prevention Trials Network, 084.

And the magnitude of the profit difference was remarkable. In the case of MSM, there was an approximately two-thirds reduction in new HIV cases compared to the control group. And among cisgender women, there was an almost 90% reduction in new infections compared to the control group. It is by far the most effective form of PrEP that has ever been developed, and it is quite an exciting advance in HIV prevention.

Jessica Bard: A good transition to my next question on new approaches to HIV treatment. Can you talk about these new approaches?

Doctor Charles Flexner: The most exciting new approaches involve long-acting parenteral or injectable antiretroviral formulations. And the only such formulation currently approved, the combination of long-acting cabotegravir, which is an integrase inhibitor, with long-acting rilpivirine, which is a non-nucleoside reverse transcriptase inhibitor, for the treatment of HIV .

Now, it’s important to point out that this combination, known as Cabenuva, is only approved for the treatment of people whose viral load has been suppressed by daily oral therapy for more than six months. So that may set the bar too high, if you will, for wider use of these exciting new formulations. But that’s how the studies were done.

There are, I think, studies going on to look at the ability to use these drugs in people who are not completely suppressed. There is, I think, reason to believe that strategies could be developed with these long-acting injectable agents that would allow them to be used in people who are not virally suppressed. But these are studies that are ongoing.

I think it is important to note that in prospective randomized clinical trials, monthly administration of Cabenuva or administration of Cabenuva every eight weeks was not inferior to the standard of daily oral care. And so, I think it provides a new option for HIV patients who don’t want to keep taking pills every day. And according to surveys and our own clinic’s experience, there are a lot of patients who are tired of taking daily oral pills and would like to switch to intermittent injection.

Jessica Bard: Yes, it is certainly an exciting time. In your opinion, what are the general messages to take away from this session?

Doctor Charles Flexner: Well, the pipeline of long-acting injectable drugs is quite rich. In addition to Cabenuva, which I mentioned, lenacapavir, which is an HIV capsid inhibitor given subcutaneously and given every six months, has shown great promise in its early clinical trials in patients heavily pretreated with multi-class resistance and in treatment-naïve patients. And this is a drug that’s now in phase three, and there’s an application to the FDA for approval of this drug for people with multi-class resistance.

There are also implants in development; for example, implants that release tenofovir alafenamide, a drug we are all familiar with, over a period of weeks to months. And there’s even transdermal delivery of HIV with what’s called microarray patches or microneedles that can create the same type of reservoir for slow-release, drugs like cabotegravir, under the skin rather than in the muscle. . And these patches, in theory, could be applied by the patient rather than being applied by a trained clinical care provider.

And so, I think there’s a lot going on in the development of a drug and a formulation that’s very exciting. I think in the next five to 10 years, the landscape of treatment and the landscape of HIV prevention will change dramatically. We’re going to be using a lot of drug formulations in 10 years that we don’t use today.

I think we will continue to learn more about how to move towards a cure for HIV. Personally, I’m not optimistic, it’s going to be easy. I also don’t think we’re going to find a cure for HIV, either through sterilizing eradication of the virus or through a so-called functional cure; that is, the virus is there, but it does not cause disease. I don’t think we’ll be able to do that in the majority of individuals anytime soon. But we’re definitely learning a lot, and I think it’s been very exciting.

Finally, vaccines against HIV will be discussed in this symposium. There are advances in the field of vaccines. Some trials have shown surprising benefits, although these are still incomplete benefits of an HIV vaccine. And we are working on new HIV vaccination approaches that may start to bear fruit in the near future. So overall, I think the take-home message from this symposium is that there’s a lot going on, there’s a lot to be excited about, that the practitioner needs to keep pace because your patients will come into the office and ask you questions about these treatments that you may not be familiar with. And so, it’s important to keep an eye on the evolution of the field and where we could go in the next few years.

Jessica Bard: There’s definitely a lot to cover during ID Week 2022, so we’re looking forward to that. Thank you very much for your time, Dr. Flexner. Thank you for being on the podcast.

Doctor Charles Flexner: Thank you Jessica. It was great to be here.

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