ATLAS and FLAIR Phase III – HIV Treatment Study

Dr. Kimberly Smith, MD. MPH, head of global research and medical strategy for ViiV Healthcare discusses 48 week data from the ATLAS (Antiretroviral Therapy as Long-Acting Suppression) and FLAIR (First Long-Acting Injectable Regimen) phase III studies of the 2 drug combination of cabotegravir and rilpivirine for the treatment of HIV-1.

As the head of global research and medical strategy for ViiV Healthcare, Dr. Kimberly Smith MD, MPH oversees the clinical development of ViiV’s pipeline assets in support of the company’s overall company strategy to deliver meaningful advances in treatment and care for people living with HIV. Dr. Smith is a graduate of the University of Michigan School of Medicine and also holds an MPH degree from the University of Michigan School of Public Health. She completed her internship, residency, and Infectious Disease fellowship at Rush University Medical Centre in Chicago. Following her training she joined the faculty of the Section of Infectious Disease at Rush University Medical Center in Chicago.

Prior to joining ViiV Healthcare in late 2013, Dr. Smith served as the Principle Investigator of the Rush University Medical Center Clinical Research Site of the AIDS Clinical Trials Group (ACTG). Dr. Smith also served as the chair of the ACTG Underrepresented Populations committee and chair of multiple ACTG clinical trials. She has been a member of NIH study sections, the HIVMA Board of Directors, the CDC Board of Scientific Counselors and numerous advisory committees.

Dr. Smith has published over 100 articles, abstracts and manuscripts and she co-edited one of the few books, HIV/AIDS in U.S. Communities of Color, which addressed the HIV epidemic among minorities in the U.S. In addition to her research activities Dr. Smith has been an active HIV clinician, clinical educator, community leader and advocate. She has lectured at countless local national and international conferences including the Conference on Retroviruses and Opportunistic Infections (CROI), the International AIDS Conference, The International Conference on Antimicrobial Agents and Chemotherapy, and Infectious Disease Society of America.

Transcript

Neal Howard: Hello and welcome to Health Professional Radio. I’m your host Neal Howard,  thank you so much for joining us here on the program once again. Our guest is Dr. Kimberly Smith, she’s Head of Global Research and Medical Strategy for ViiV Healthcare and she’s joining us here on the program to talk about some data from the ATLAS and the FLAIR Phase III studies for treatment for HIV. Thanks so much for joining us on the program today Dr. Smith, thanks for taking the time.

Dr. Kimberly Smith: Thank you for having me.

Neal: Well I personally haven’t heard, not nearly as much about HIV here in recent, for the last couple of years as I have in the past. Give us a bit of your background and talk about your HIV research.

Dr Smith: Sure. Well I’m an infectious disease physician. I worked for 20 years taking care of patients with primarily HIV in Chicago and in 2013, I joined ViiV healthcare to lead the research for this organization. Viiv Healthcare is a company that is, really the only company that’s 100% focused on HIV so all we do is make drugs for the treatment and prevention of HIV.

Neal: And as I said, I personally haven’t heard as much about it as I did in the past. Is HIV still as prevalent as it was say five-six years ago?

Dr Smith: Well unfortunately, yes. In the United States, I mean there are more than a million people who are living with HIV disease. There are over 30,000 individuals who are newly diagnosed with HIV disease each year and that’s been fairly flat over the last, really throughout the last few years or so and so it really continues to be a challenge that our country faces and is a worldwide challenge. As you probably know that there are more than 37 million people in the world of them with HIV, the overwhelming majority of them are in sub-saharan Africa. However,  HIV really doesn’t stay anywhere, it is it is a global epidemic.

Neal: So needless to say it is just as ominous as it has ever been even though some in the media don’t focus on it as much as some of the other thing to I guess cause more fervor and  error of course.

Dr Smith: Yeah, part of why it has gotten less attention is that there are some I guess a miss. People who are believing that somehow HIV is cured or that it’s not a problem anymore because of treatment and the reality is is that as I mentioned there continue to be people who are with HIV… however… it is for people who have access to treatment it’s not a death sentence in the way that it was in the past. It still is a significant issue and the notion of taking medicine sort of for the rest of your life continues to be a challenge which is part of why the work that we’re doing we think it’s so important because what we’re trying to do at ViiV this actually make HIV treatment sort of a less complicated, a lesser part of people’s lives in general and so that  kind of brings us to the HIV study.

Neal: Now the Atlas and the Flair studies, what it stands for something as does Flair. Talk about what these studies are and in the treatment of HIV.

Dr Smith: Sure. So … our Phase III pivotal studies for Cabotegravir and long acting Rilpivirine for treatment of HIV. And so what is long acting mean? Well you think about most HIV medicine,  even though we’ve made a lot of progress and have gotten to the point where people can take as little as one pill a day, taking a pill everyday for the rest of your life is still a challenge for some people and a lot of people describe themselves as sort of feeling like every time they have to take the pill, they’re reminded of living with HIV and they want to be able to move on with their life. And so long-acting therapy with Cabotegravir and Rilpivirine allows individuals to actually take an injection once a month instead of a pill every day. And so these two pivotal studies ATLAS and FLAIR were really designed to compare that combination of Cabotegravir plus Rilpivirine versus standard of care regimen to determine if these long-acting therapies, again injections once a month compared to daily pills could be just as good. And to cut straight to the chase actually, we did demonstrate that the injection, the long-acting therapy works just as well as taking a pill everyday.

Neal: Now that it’s interesting that you mentioned some psychological reasons for non-compliance, whether severe non-compliance or just a small amount. What is it about the injection and I guess the simplicity of the injection as opposed to the psychological difficulty of taking a pill everyday as opposed to taking an injection every month for the rest of your life or is that the case?

Dr Smith: Yeah. Well I think what we all recognize is that HIV is a disease that from the beginning of the epidemic was very stigmatized. People were judged as having done something wrong if they acquired HIV and we all know that that’s not the case and that people shouldn’t be judged but there continues to be stigma so people have stigma that they experience from others but there’s also what has been described as self stigma. So individuals feel guilty or they feel  like somehow they’ve done something wrong because they’re living with HIV disease and as much as they can hear from others that they have no reason to feel guilty, they still have that and so that self stigma is part of what I mentioned when patients describe sort of the idea of taking away that daily pill and that daily reminder of HIV, that is something that’s very appealing to patients.

Neal: Now this combination of drugs, aside from the management of the HIV, what about side effects? Are there any physical side effects that don’t present with the injectable as opposed to the daily pill?

Dr Smith: Sure. So let’s first talk about what are the side effects, the general side effects that we see with daily oral therapy. Because we’ve made a lot of progress, the medicines are tolerated a lot better than they were in the beginning. Everyone remembers the days of people having to take 20 pills a day and having terrible nausea and diarrhea and really terrible symptoms and so those medicines that caused those symptoms aren’t used very commonly anymore. The pills that are used nowadays, people have maybe still a little bit of nausea occasionally, they may have some of the more long-term impact of being on medicine like renal to kidney disease or bone disease or cardiovascular disease so they are associated with more long-term side effects as opposed to short-term side effects or immediate side effects as they were in the beginning. The injection therapy in this first year of individuals being on therapy, the most common adverse event or side affected individuals experience was actually an injection site reaction so pain at the site where they get the injection. Other than that, there were not really any other adverse events they really stood out for individuals on the injection.

Neal: Were there any subjects who were just fine with the daily pill but they were given the injectables just to see if they would prefer or if it made no difference to them personally?

Dr Smith: So actually all of the individuals on the study were just that, individuals who were doing well on oral therapy. So let me describe the studies maybe and then we can just sort of dig in a little bit. So the ATLAS study we’ll talk about first, so that study took individuals who were on therapy and stable on therapy for an average of four years. So these individuals had been doing well on their oral therapy for a long time and they were randomized to stay on their oral therapy versus a switch to the long-acting Cabotegravir plus Rilpivirine. And in that study,  we looked at how many of those individuals maintained biologic suppression and how many individuals had biologic failure and I can tell you that it’s actually less than 2% of individuals on the long-acting so 1.6 percent of those individuals actually failed therapy compared to 1% who stayed on their original therapy. So really very little difference, less than one percentage point difference and so that show non-inferiority of the long acting regimen. So that was the ATLAS study, the FLAIR study was a little bit different and that individual came into this trial, they had never been on treatment before and so they all started on one particular treatment, one fix dose tablets that contained a pack of abacavir, 3TC and dolutegravir in one pill. Everybody started on that until their virus got to be undetectable after 20 weeks, those with who had an undetectable viral load were randomized to staying on that single pill versus going on the long-acting injectable Cabotegravir Rilpivirine. And in that study, the proportion of individuals who experienced biologic failure was around 2% so in the long acting arm, it was 2.1% compared to the tablet or the oral therapy which was 2.5% so a difference of 0.4% favoring the injection. And so when you combine these two studies, it really shows that there really was no significant difference between the long-acting therapy and being on oral therapy. And again this is starting out with in comparing individuals who were doing well on therapy already and so then you ask the question about preference and we ask that question to patients as well. We ask patients specifically since they had been on oral therapy and on long-acting therapy – which one did they prefer? And in one study, 99% of individuals said that they preferred the long-acting and in the other study, it was 97 percent of individuals. So there’s no question that individuals who had this opportunity to be in this trial and switch over to long-acting therapy preferred that over a daily pill.

Neal: Where can our listeners go online and get some more information about ViiV Healthcare and about these studies, the ATLAS study as well as the FLAIR?

Dr Smith: So these studies were presented at the Conference on Retroviruses and Opportunistic Infections or CROI and so if you go to the CROI website, you can actually see the details of the abstract are actually available, you can look that up. But there’s also a number of, even if you just sort of googled ‘Cabotegravir plus Rilpivirine’ or googled ATLAS and FLAIR HIV studies, you could pull up a number of articles that have been published. We think over 70 articles were written focused … and talked about the FLAIR and ATLAS studies so they even just use, as some folks call it, the Google machine, you could find a lot of information about ATLAS and FLAIR. And if you want more information about these, individuals can find us at viivhealthcare.com

Neal: Thank you Dr. Smith.

Dr Smith:  Thank you for having me and have a good day.

Neal: You’ve been listening to Health Professional Radio. Transcripts and audio of this program are available at hpr.fm and healthprofessionalradio.com.au and be sure and visit our Affiliate Page when you visit our platform at hpr.fm and healthprofessionalradio.com.au

 

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