Switching Therapies in Patients Who Are Successfully Treated

Segment Description: Infectious disease experts provide insights into switching therapies for patients who have been successfully treated and the various 2-drug combinations used.

Interview Transcript (modified slightly for readability):

Joseph Eron, MD: Ian, can you discuss the patient in your practice who is currently on treatment and either has a complication or not and you’re considering switching therapies? What is your approach, and how do you optimize their regimen?

Ian Frank, MD: This is the most common treatment decision that I make in my practice. I’ve been taking care of people with HIV for a long time. Most of the newly diagnosed patients see the younger physicians in our practice.

I look at the anti-retroviral regimen of every patient and decide if I am able to improve his or her combination. I want to make things simple with a few pills, convenience, and flexibility. I want my patients to be able to take their drugs during the day, not just at night with food or on an empty stomach. For patients who have no symptoms on a regimen that is not a preferred regimen, I try to switch them to a preferred regimen.

I want to get them onto an integrase inhibitor—based regimen and cut down on the number of pills. There are many options to choose from. We have resistance testing that could look at archive mutations in HIV DNA for our patients who have failed in the past or come to us from another practice with an unclear history. The goal is to detect any baseline resistance prior to switching therapy if resistance tests are not available to us.

There are agents of next generation in RTIs [reproductive tract infections]. We have next-generation integrase inhibitors. There are options for people who have failed on some of the earlier agents within therapeutic classes. There are effective 2-drug combinations. Other options include [dolutegravir lamivudine]—[dolutegravir rilpivirine] for people who have not failed on an integrase inhibitor–based regimen before, as well as the standard 3-drug combinations that have all been proven effective in the context of switching somebody with biologic suppression.

Joseph Eron, MD: Colleen, are the 2-drug combinations safer in people that are securely suppressed?

Colleen Kelley, MD, MPH: Absolutely. And that’s where I’m doing most of my 2-drug combinations. Generally, I still see very advanced disease. So initiating 2 drugs still makes me a little nervous, similar to the adolescent questions. When someone is suppressed and they don’t have ongoing replication, the amount of drug pressure they need is less than their initial start. Oftentimes, I will drop them back to 2 drugs once they are stable. We can reduce the pill burden sometimes. We can eliminate drugs that may have long-term adverse effects or may be interacting with other medications that they’re taking. This is the setting where I use a 2-drug regimen.

Allison Agwu, MD, ScM: Previously we only had single tablets that had 3 drugs, and there are people where that third drug probably wasn’t effective.

Joseph Eron, MD: Yes.

Allison Agwu, MD, ScM: Because that third drug was never really working, we reassess and realize they could benefit from a [dolutegravir rilpivirine] regimen. I’ve done that. I take care of a lot of perinatal patients who acquired [HIV] in their 30s, and their nukes are not active.

Allison Agwu, MD, ScM: Exactly.

Joseph Eron, MD: And then you can give them a regimen that has neither.

Allison Agwu, MD, ScM: Yes, [for] 34 years old [we use] a 1-pill regimen. That’s been effective for those patients.

Joseph Eron, MD: My mantra has been “the simplest, safest regimen that fits in a person’s life.” And forcing myself with every patient I treat to do that little calculation. Is this really the simplest and safest thing they could be on? Did you know virological failure is toxic? It’s an adverse effect, so we want to be careful.

Ian mentioned that you could do some testing to look for previously present resistance. It’s important to find all the old genotypes and do things that make clinical sense. I do believe we can get patients into some pretty safe places. Especially those who are on very complicated regimens.

Joseph Eron, MD: I recently had an 80-year-old woman who was on 3 drugs. She’d never been on 2 drugs or nucleoside therapy. She had always been on 3 drugs. She’s been suppressed since 2012 or 2011, and she had osteoporosis. And you know, whether it’s TAF [tenofovir alafenamide] or TDF [tenofovir disoproxil fumarate], does she really need that?

Colleen Kelley, MD, MPH: Right.

Allison Agwu, MD, ScM: Exactly.