High-Resistance Therapy Options for Treatment-Naïve Patients With HIV

Joseph Eron, MD, Daniel R. Kuritzkes, MD, and Monica Gandhi, MD, MPH, discuss the likelihood of other combination regimens for the treatment of multidrug-resistant HIV, including monoclonal antibodies.

Joseph Eron, MD: Monica, are any of these options that we talked about available for treatment-naïve people?

Monica Gandhi, MD, MPH: That’s a good question. With fostemsavir, what’s the point? For maraviroc, no. It’s not that potent of a drug, remember. Raltegravir with maraviroc has been examined, but never in naïve patients. We use twice-a-day dosing unless you have ritonavir in the background, which can make it once a day. I wouldn’t do that. With ibalizumab, why’d you do IV [intravenous]? But for lenacapavir, the CALIBRATE study has the question of whether you can give lenacapavir with either bictegravir, TAF [tenofovir alafenamide]/FTC [emtricitabine], or TAF [tenofovir alafenamide]—the same drug company makes these medications. We may have put lenacapavir with other things, but that’s what they’re studying with it: those different components of bictegravir or TAF/FTC [tenofovir alafenamide/emtricitabine] taken out or bictegravir or TAF/FTC [tenofovir alafenamide/emtricitabine] itself as a background. In CALIBRATE, we have 54-week data. It’s looking good for all 4 of those arms, but you’re still going to have to remember to take the oral pill because you’re not multidrug resistant. These are naïve patients, so maybe there’s more forgiveness. Then you can give lenacapavir subcutaneously.

I want to remind us that lenacapavir is in trials for PrEP [pre-exposure prophylaxis]. We say we can’t use 1 drug, but we can in PrEP. That’s an exciting idea, 26 weeks and then your pre-exposure prophylaxis. Now we have cabotegravir IM [intramuscular injection] every 8 weeks for PrEP, and already it was very much superior in all populations studied because it’s easier to do that than take daily pills.

Joseph Eron, MD: It’s definitely easier to do.

Monica Gandhi, MD, MPH: Especially for preventive medication. I’m very hopeful about the PURPOSE 1 and PURPOSE 2 trials, which show lenacapavir.

Joseph Eron, MD: Dan, do you want to say anything about monoclonal antibodies? We now have some that could potentially be given every 6 months. Do you think that will be in combination with lenacapavir? Do you think there’s hope for that, or do you think that’s a stretch?

Daniel R. Kuritzkes, MD: There’s hope, which is a stretch. There are whole series of these monoclonal antibodies, which we often call broadly neutralizing HIV-1 antibodies [bNAbs] because they’re able to neutralize so many strains. The problem is that the best of these get to 85%, 90%, maybe 95%, and you can’t know whether the patient’s virus is susceptible without getting a test, and that’s a major undertaking not clinically available. If these antibodies were to be used, I don’t think they ought to be used in viremic people. They might be used in switch, where someone is already suppressed. They probably need to be used in combination. Whether you could do an antibody with another longer-acting drug is being studied, and that’s an important thing to study. I’m not as hopeful as I was a few years ago.

Joseph Eron, MD: The virus always seems to stay a little ahead of us even as we look at the population of viruses over time. I know this has been looked at for subtype C anyway. Over time, even with these bNAbs that were isolated, the virus population seems to be getting a little less susceptible over time.

Daniel R. Kuritzkes, MD: We’ve learned so much from our experience with COVID-19 and how these antibodies, which were developed and were so effective at treatment or prevention, then lose their activity because the virus moves on. We’re going to see the same thing.

Monica Gandhi, MD, MPH: That’s a good way to put it.

Joseph Eron, MD: The virus moves on.

Transcript Edited for Clarity

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