Efficacy, Safety of Virologically Suppressed Adults With HIV Switching Treatment From B/F/TAF to Dolutegravir/Lamivudine
In this podcast, Charlotte M. Rolle, MD, MPH, discusses her team's research that evaluated the efficacy and safety of switching HIV treatment using bictegravir/emtricitabine/tenofovir alafenamide to dolutegravir/lamivudine. Dr Rolle spoke about this topic during her poster presentation at IDWeek 2023 in Boston, Massachusetts.
Additional Resource:
Rolle CP, Castano J, Nguyen V, Hinestrosa F, DeJesus E. Efficacy, safety and tolerability of switching to dolutegravir/lamivudine in virologically suppressed adults living with HIV on bictegravir/emtricitabine/tenofovir alafenamide -the DYAD study. Talk presented at: IDWeek 2023. October 11-15, 2023. Accessed on September 20, 2023. https://idweek.org/
For more IDWeek 2023 conference coverage, visit the Resource Center.
TRANSCRIPTION:
Jessica Ganga: Hello everyone, and welcome to another installment of Podcast360, your go-to resource for medical education and clinical updates. I'm your moderator, Jessica Ganga, with Consultant360, a multidisciplinary medical information network. Dr. Charlotte Rolle joins us today to discuss her team's poster presentation at IDWeek Conference 2023.
Charlotte Rolle, MD, MPH: Awesome. Thanks, Jessica for having me. My name is Charlotte Rolle. I'm an adult-trained infectious disease physician, and I'm the Research Director at the Orlando Immunology Center, which is a private practice infectious disease clinic in Orlando, Florida, that serves the needs of about 4,800 people living with HIV.
Today we're actually going to be talking about a study that we did here at the OIC that was presented at the recent IDWeek Conference looking at the efficacy and safety outcomes of virologically suppressed people living with HIV on bictegravir/emtricitabine/ tenofovir alafenamide, also called B/F/TAF that were switched to dolutegravir/3TC.
Jessica Ganga: Please provide an overview of your session that you presented at IDWeek.
Dr Rolle: Currently, right now in the literature there are a few studies that have evaluated the switch in virologically suppressed adults from B/F/TAF to dolutegravir/3TC. However, a lot of those studies are observational studies and very few of them are actually large randomized controlled trials. So there was a need in our field to actually do a formal randomized controlled trial evaluating whether that switch was effective, whether it was safe, and whether it was a feasible and reasonable switch for patients living with HIV. So that was the premise behind this study.
We ended up randomizing 222 adults in an open label fashion who had been stably suppressed on B/F/TAF for at least six months to either switch to dolutegravir/lamivudine or continue on B/F/TAF. The primary endpoint of the study is virologic failure at week 48. However, at IDWeek we did an interim analysis and presented our secondary endpoints of virologic failure and safety outcomes at week 24.
Overall, the study population was well-balanced in both study arms, and so our randomization was very effective. I'm very proud of the fact that about 50% of the study participants were people of color and about 16% were women because we know that those populations are traditionally very difficult to recruit in HIV clinical trials. Overall, at week 24 we saw a non-inferior efficacy in switching to dolutegravir/lamivudine versus continuing B/F/TAF in stably suppressed adults with very low rates of virologic failure in each study, 2 versus 4%, which ended up meeting the non-inferiority margin that was initially set at 6%. Overall, at week 24, even though we're not at the primary endpoint yet, we're getting an early look at the data, and so far the data are proving non-inferior efficacy.
Dr Rolle: In our study, we did have seven individuals that met the protocol defined criteria for confirmed virologic withdrawal, and in this study that was two consecutive viral load measurements greater than or equal to 50 copies. Of those 7 CVWs there were two that actually had evidence of resistance to the components of their therapy on the genotype performed at the CVW visit.
There was one individual in each study arm, one in the dolutegravir/3TC study arm that had a treatment-emergent or what we think is a treatment-emergent M184V, and then there was also an individual in the BIC/F/TAF arm that also had an M184V in addition to a G140S. What is interesting is that neither of those participants had a baseline genotype available at steady entry, and therefore it is actually a little bit difficult to comment on whether those mutations are truly treatment-emergent or not. There was unfortunately also a third participant in the dolutegravir/3TC arm that did not meet the definition for confirmed virologic withdrawal, but rather had a genotype performed at an initial episode of unconfirmed viremia and was also found to have several NRTI mutations that affected the activity of lamivudine, including an M184V and K65R. That participant unfortunately did have to be discontinued from the study and treated as someone who had treatment-emergent resistance despite the fact that they were not a formal CVW.
Overall, from a safety standpoint, we did observe more drug-related adverse events in the dolutegravir/3TC arm. However, this was an open label switch study, and this is a finding that's commonly seen in open label switch studies when participants know that they are being switched to a new medication versus continuing a medication that they've been on for quite some time, and so we did see that. However, the safety profile in terms of the most commonly observed adverse events were consistent with the known safety profile of dolutegravir/lamivudine. We saw most common adverse events that were not surprising to us, GI disturbance, dizziness, insomnia. These are adverse events that have been well described with the use of dolutegravir/lamivudine in other clinical trials.
Dr Rolle: We also did take an early look at changes in renal and metabolic parameters at week 24 and found no significant differences in changes when we were looking at both study arms. We looked at parameters of interest such as creatinine, GFR, lipid panels, weight, BMI, and waist circumference.
Overall, I think what we have here is an actual formal randomized controlled trial in virologically suppressed patients evaluating a switch to dolutegravir/lamivudine versus staying on BIC/F/TAF. Early we're seeing non-inferior efficacy. We're seeing no significant difference in terms of some important renal and metabolic parameters. We are seeing more adverse events in the investigational arm from a safety standpoint. However, this is to be somewhat expected with an open label switch study.
I think overall our study does reinforce findings that we've seen from prior clinical trials such as TANGO and SALSA, which does suggest that switching to dolutegravir/lamivudine is a feasible option compared to continuing some of the modern three-drug integrase inhibitor based regimens that are available to our patients, and our data are supportive of other trials looking at switches in similar populations.
Jessica Ganga: Thank you so much for that, Dr. Rolle. What learning objectives do you believe the audience took away from your session?
Dr Rolle: I think that given that we know that BIC/F/TAF is the most commonly prescribed antiretroviral in virologically suppressed adults living with HIV, there has always been a question of whether there is a need to switch to a two-drug regimen versus continuing a three-drug regimen. I think a learning objective and the primary learning objective of our study is because we actually saw no differences in terms of efficacy and important metabolic parameters, it would appear that not only is the switch feasible, but the switch is also not going to cause any harm. I think that when evaluating whether a third drug is actually needed to maintain suppression in stably suppressed patients, our study provides education that may not necessarily be the case for the vast majority of patients.
Jessica Ganga: What barriers do you believe people may face when switching to dolutegravir/lamivudine?
Dr Rolle: That's a great question, and it's sort of interesting in that I think that there are barriers in the opposite direction. One of the claims to fame of two-drug regimens is because of the fact that they actually contain less drug, they tend to be cheaper and better covered by insurance. What we actually observed in our clinical trial was no significant access barriers.
I'm not sure if a lot of people know, but our study, even though it was funded by ViiV Healthcare, the protocol was developed and designed by us investigators here at the OIC with no significant input from ViiV on the study design. ViiV did not supply the study drug. People actually accessed the drug through their own commercial insurance plan.
One of the things that we tracked in the study was whether someone was not going to be able to get dolutegravir/lamivudine because of an insurance denial or a need for a prior authorization. Of the 170+ switches that we had in this study, we had no one had dolutegravir/lamivudine denied from an insurance standpoint. We know that the wholesale price of the drug is cheaper than other three-drug regimens. So again, it's an interesting question because I don't anticipate barriers to switching to a two-drug regimen. You may actually get some barriers in the opposite direction switching to a regimen that is more costly.
Jessica Ganga: What are the gaps in research on treating virologically suppressed adults living with HIV?
Dr Rolle: I honestly think that the virologically suppressed adult population living with HIV in the United States is relatively well studied at this point in time. I think that there are still some hot topics and key data gaps when you're thinking about the population. I think the elephant in the room is sort of the metabolic data gaps that we have. Unfortunately, a lot of our modern antiretroviral regimens have, we think contributed to some unwanted weight gain in our patients, especially in certain patient populations. We as a field have been trying to answer the question of which drugs are really the culprits. Are there drugs that we need to stay away from? Are there drug switches that we can do to help out with the weight issue? When our patients are gaining weight, are there more long-term cardiometabolic consequences of that weight gain? If so, which drugs are implicated in those?
I think those are questions that we're starting to answer. Some of the more recent data presented at both IDWeek and IAS, there was some very interesting studies attempting to answer those questions, but it certainly is something that remains to be seen. We don't have any concrete answers about the culprits of weight gain in the stably suppressed patient population. So I think everyone's just kind of waiting with bated breath and staying tuned. There are some important randomized controlled trials that will be forthcoming that will really help us elucidate the answer as to whether switching off certain drugs causes weight loss, so that's one big thing.
The other is pregnant suppressed patients. We continue to have a paucity of data among our pregnant patients in terms of pharmacokinetics, efficacy and safety of antiretrovirals in pregnancy, especially our modern antiretrovirals, the drugs that are recommended for most people living with HIV. We have no idea whether they're safe in pregnancy. We just have not accumulated enough data in that group. Those are really the two big data gaps that I think of when it comes to the stably suppressed population.
Jessica Ganga: Is there anything else that you'd like to add?
Dr Rolle: No, Jessica, I don't think there's a whole lot to add at this time. I definitely want to thank you for allowing me the opportunity to talk about our study and what we found. Again, I will mention that this was just an early look at the data week 24. Our primary outcome is definitely at week 48, and so we are hoping to present those results at a future upcoming conference, and I would just tell anyone in the audience who's interested to stay tuned.
Jessica Ganga: Well, thank you again, Dr. Rolle. We'll be looking for those results when they do come out. You have a good rest of your day.
Dr Rolle: Thank you, Jess.