touchINFECTIOUS DISEASES coverage of data presented at CROI 2024
Integration of the latest data in antiretroviral management of HIV, challenges clinicians may face when adopting new strategies and updates from the Conference of Retroviruses and Opportunistic Infections (CROI) 2024 are reported here by Dr Eric Daar, Division of HIV Medicine, Harbor-UCLA Medical Center, Atlanta, GA, USA.
Dr Daar begins by discussing how the latest data in antiretroviral management of HIV could be integrated into clinical practice and the challenges clinicians could face in adopting these new strategies. Dr Daar highlights how long-acting injectables require clinic administration and vigilance for sustained efficacy and resistance, whilst weekly oral treatment regimens show promise but require careful patient selection and adherence support. Finally, he provides key insights into future developments and how they may include longer-acting medications administered every three to six months, streamlining treatment and enhancing patient convenience, albeit requiring ongoing research and careful patient selection.
Disclosures: Eric Daar is a consultant for Gilead, Theratechnologies, and ViiV Healthcare, and receives grant/research support from Gilead and ViiV Healthcare.
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Transcript:
I’m Eric Daar, the Chief of the Division of HIV Medicine at Harbor UCLA and Professor Medicine at the Geffen School of Medicine and UCLA.
How can the latest data in antiretroviral management of HIV be integrated into clinical practice, and what challenges might clinicians face in adopting these new strategies?
It’s a really important question, just because we have new drugs at work in clinical trials, actually implementing them into clinical practice raises new challenges. We all recognize that with the long acting version 1, implementing long acting cabotagriver/rilpivirine is easier said than done. One, you need to make sure that you know how to screen people, at least the way it’s currently indicated based on the data, they have to be virologically suppressed, no history of virologic failure, or resistance to the active drugs and the regimen. Then you have to get them used to coming in every four or every eight weeks for an injection. Right now those injections have to be given an clinic environment, because they are two intergluteal injections, which cannot be self-administered at home. So you need to set up a system that allows you to do it. More importantly for the patients, you also need to put in place a system that assures that the person is coming back for their regular injections. These drugs have a long half life and they can be present in the body at certain levels for up to a year. You need the two of them to maintain suppression, but the half lives aren’t the same. So at some point over many months, one of the drugs will have been cleared from the system, the other drug will persist. Therefore, it it is a perfect setting to select for resistance to things like integrase inhibitors. So in implementing it, we need to have the systems in place in our clinics, but we also need to know how to select the right people and be actively reaching out to them if they don’t come back for their regular visit, which has been an issue for even the every eight week dosing, which needs paying close attention to, or we can do harm. It is one of the reasons why people have been a little concerned to extrapolate the experience in pristine clinical trial patients to poorly adherent patients. We now have data that suggests with an intensive effort that we may be able to do that to help people.
When do we start to think about the next steps and what’s on the horizon with weekly pills? Right now, we have phase two data, 24 weeks follow-up, and we need 48 weeks and beyond. We need larger datasets, which is actually now happening. There are clinical trials that have either started or will be starting soon. One of the key things we’ll be looking at in these trials is whether, one, people achieve suppression and tolerate it – I think there is a good chance that is true based on the early data, but also in those who don’t maintain virologic expression, do they fail with resistance? Right now, the bar for standard therapy with three drugs is that nobody fails with resistance practically – so the bar is going to be high. We also know with our standard three drug regimens right now that they’re fairly forgiving. We don’t tell people that they can take it less than once a day, but we certainly have many people in our clinics who do miss a dose here, miss a dose there, and the drugs are pretty forgiving for probably a variety of reasons. One might imagine that even if the weekly therapy achieves that goal of maintaining high levels of suppression with low risk of emerging resistance that they may not be as forgiving.
When you’re taking a drug once a week, if you miss one dose, that means now you’re taking it every other week, therefore I think we’re going continue to have to follow the data, but be extremely careful in who we select to be on these regimens, maybe a little higher risk. For people with poor adherence, and what plan we put in place, we can to reach out to them and identify poor adherence early, and to try to assist them in addressing whatever the reasons are they’re missing their doses so that they aren’t at risk for developing more resistance.
What future directions do you foresee for antiretroviral management of HIV, and what areas require further research?
The next step, are in my eyes, version two, long acting therapy, which is going to be an every three, four, or six month treatment. I think the weekly therapy is going to get there quicker. And that’s a big advance because it’s oral medication and injections aren’t for everybody. We currently have lenacapivir, an every six month injectable. Which is not currently recommended for self-administration, you have to come into the clinic, but coming in twice a year is different than every four or eight weeks, and therefore we need a partner medication. Right now, we don’t yet have another every six month drug. The closest we have to it are some of the modified long-acting monoclonal antibodies that can be given every six months.
We have seen a little bit of data showing that if you use them carefully in the right people and perhaps in combinations, that they may be a viable option. There was a presentation at CROI 2024 demonstrating results, from a follow-up presentation from a previous study, where they actually used two monoclonal antibodies in people whose virus was was susceptible to them every six months, along with lenacapivir, showing at least during short term follow-up, regimens that could potentially be given every six months, maintain virologic suppression.
My guess is that’s going to be the next major step in antiretroviral therapy, and while injectables may not be for everybody right now, it’s possible every six month injectables could get even more traction than the every two month injectables currently available. That would pretty pretty amazing if you only had to think about your treatment twice a year. Literally two days a year.
Interviewer/Editor: Katey Gabrysch
Cite: Daar E. Antiretroviral management of HIV in clinical practice: integration of the latest data. touchINFECTIOUSDISEASES, March 19 2024.
