Battling Resistance to HIV Therapy: New Drugs in the Pipeline

Joseph Eron, MD, professor of medicine at the University of Carolina at Chapel Hill, explains how some individuals acquire resistance to HIV therapy and discusses new drugs in the pipeline that are effective against resistant virus.

Interview Transcript (modified slightly for readability):

Resistance to therapy is now becoming less and less common, which is great. In fact, the trainees that work with me complain that they don’t get enough experience treating patients with resistant virus.

There are essentially 2 ways that a patient with HIV gets exposed or acquires resistance. One is that it can be transmitted; you can get a resistant virus from somebody else. The good news is, most of the transmitted resistance that we see now is easily covered by our recommended initial therapy. You can get a resistant virus, but in general, the vast majority of those are pretty easily treated. The other way, of course, to get a resistant virus is if you don’t take your medicine consistently. Over time, the virus can become resistant if it’s exposed to low levels of medication; the virus replicates in the presence of medication and that leads to resistance. The good news, again, is that with many of our first-line therapies, it’s very difficult to develop resistance. If you’re taking some of it—even if you’re not perfectly adherent—you usually maintain suppression. Another group is people who have been on therapy for years and years who had a resistant virus from when we didn’t have medicines that are as good as they are now, and when medicines were given less frequently, were less effective, or people had more trouble taking them.

There are new drugs being developed, too; we have several new drugs that have come on line in the past few years and they’re very effective against resistant virus. There are at least 2 drugs that are approved or are very close to getting approved that will also work against resistant virus. One that has recently been approved is a monoclonal antibody called ibalizumab; it blocks binding of the virus to the CD4 molecule so that the virus can’t enter the cell. Ibalizumab has to be given as an infusion, and so, it’s not perfect for everybody, but it has been clearly shown to work in people with resistance to other medications. The other drug that is pretty close to approval is fostemsavir that also blocks the attachment of the virus to the CD4 cell; that’s a pill, which is good, though it is a twice-a-day pill. And, again, it’s been shown clearly to be effective against resistant virus. And so, for those people—which is a small number—who don’t have a viable treatment right now, those drugs will be very useful for them.”