Ryan Haumschild, PharmD, MS, MBA: Let’s discuss available pharmacotherapeutic options for the treatment of multidrug resistant HIV [human immunodeficiency virus], as well as the importance of maintaining appropriate background therapy and the impacts of CD4 recovery. Dr Sension, I’d like to start with you. Until now, what have been the generally accepted strategies for treating individuals with multidrug resistant HIV, and are there certain regimens that would be considered first-line therapy for these instances?

Michael Sension, MD: I think we start with an assessment of resistance, and indeed there are resistance tests, which result in telling us what specific mutations may be present in someone’s virus, and then which of those mutations are associated with a decreased susceptibility or resistance to what drugs. In other words, what drugs won’t work and what drugs will work? We start with those results, and then we try to put together a regimen using what may still be susceptible, what may still have activity and we can use, and pair it with hopefully something that’s new, perhaps a new target, a new medication, a different way of using an existing medication. Some medicines can achieve higher levels at higher doses or different types of dosing to overcome resistance.

Certainly, when we have a new class of drug that’s been approved, that represents an active agent that we know will work against somebody who has developed resistance to previous classes that they’ve blown through. It’s very important, I think, to protect that new drug that we’re going to use with what is often referred to as a background regimen. Something that can be put together with whatever new fully active drug we think we have to create a new regimen that will lead to virologic suppression, give us our very best chance at achieving virologic suppression. There have been many drugs that have been developed, and often fast-tracked by the FDA for approval, for people who have very few options, who have multidrug resistance. In medication after medication that has been approved, I think the principle has been the same. If you use it as monotherapy when you have no other options to pair with it, you get the least response, not zero, but you get a much better response when you’re able to pair whatever your new core agent is with something else that can go with it. I think that’s what we’re talking about as an optimized background regimen to go with a new core agent to hopefully create something that’s completely virologically suppressive.

Ryan Haumschild, PharmD, MS, MBA: You did a great job talking about the background regimen. I think that’s so important. That’s kind of the backbone of the treatment, and then we add that innovative therapy. We’re seeing that a lot I feel across a lot of therapeutic areas, these combination therapies and as you mentioned, giving that patient the best chance at viral suppression up front. How do we do that in a way that they stay compliant? Dr Sension, you described the importance of maintaining that appropriate background recommendation, and why we need to optimize the regimen in order to preserve the best chance of therapy. If you could, discuss a bit further, how does maintaining a background regimen in addition to potentially other therapies impact the complexity of the disease? And are there any specific background therapy regimens that should be avoided for instances of multidrug resistant HIV?

Michael Sension, MD: I think the key is to have an active background, something active in the background regimen. Historically we’ve tried to include nucleoside reverse transcriptase inhibitors, but I think that may not necessarily be the case given what we have more recently available to us. I think the key is to try to find something that may have either full or partial activity within the historic classes of drugs that we’ve had available to us over the last several years, whether it be nucleoside reverse transcriptase inhibitors, protease inhibitors, NNRTIs [non-nucleoside reverse transcriptase inhibitors]. If we could find something that has some degree of activity and pair it with one of these newer, more novel medications, such as different types of attachment inhibitors, fusion inhibitors, and capsid inhibitors. I know we’ll get into that at some point, but I think it’s important to pair something with it. Indeed, clinical trials have led to the approval of these more recent drugs, as well as integrase inhibitors. We’ve seen the dolutegravir activity when used in people with multidrug resistance is benefited by having an optimal background regimen. If you have zero fully active drugs to pair with whatever you’re adding, you get less of a response.

Transcript edited for clarity.