Real People, Real Change:
Dr. Douglas Cunningham
An investigator of the EMERALD study reviews Week 48 data.
Patient: I always think like God why me? It’s still hard. Every day when you take a pill, you’re reminded of it. I’ve been living with HIV for 10 years.
Dr. Douglas L. Cunningham, DO: My name is Dr. Doug Cunningham, and I’ve been practicing in the Phoenix area for the last 30 years. We have a large HIV population in our practice of about 2,000 patients. Our patients are very diverse as well. We take care of patients that are gay, straight, bisexual, and transgender. That being said, all of these populations have unique types of situations. So many of them have been marginalized. Some of them have psychosocial issues. Some of them have substance abuse issues. Some of them are homeless, and for that reason, each of them are unique and I strive to make a meaningful difference in these people’s lives.
Patient: I was diagnosed over 10 years ago. I can’t remember the exact time frame because I try to put it behind and I think about it too much, but it was definitely a scary moment in my life where I thought it was ended. You know what I mean, I thought it was over. I was alone. I was actually on my lunch break, so I actually had to go back to work and put on my poker face I guess and try to get through the rest of the day, which was really hard. I thought how could this happen? You know? Being a straight African American woman living with HIV it’s really tough trying to find support. Especially when you’re dating, it’s definitely hard because a lot of people are very ignorant and don’t know about it, so they just automatically kind of think whatever negative about you. rather than trying to be more open and understanding and maybe research on their own. The treatment that I was on before required that I had to take three pills every single day, so it’s hard to get used to.
Dr. Douglas L. Cunningham, DO: The Department of Health and Human Services guidelines provide an overview of scenarios for why or when a switch is sometimes considered. Simplification is one of the reasons why I switch my virologically suppressed patients. Tolerability is another common reason why I may switch my virologically suppressed patients’ treatment.
Dr. Douglas L. Cunningham, DO: A virologically suppressed patient that I switched had been on an integrase regimen, working many hours and he had some weight gain, headaches, couldn’t sleep at night, and he says I only want to be on a single tablet.
Dr. Douglas L. Cunningham, DO: My goal as a provider is not only to get my patients to undetectable but help them stay undetectable with a regimen that they can tolerate and take as prescribed daily. Most common adverse effects seen with antiretroviral therapy per the DHHS guidelines include the following that are here that are listed. The choice of therapy when switching a virologically suppressed patient is extremely important and should focus on the primary goal of antiretroviral therapy. Maintaining virologic suppression, while preserving future treatment options. If after switching a regimen the patient experiences virologic failure and new resistance mutations emerge, the patient may require more complex or expensive treatment options. Before switching, it’s important to have a full picture of the patient’s history. Some things to consider are their past virologic responses, antiretroviral-related toxicities and intolerances, and their cumulative resistance test results.
Dr. Douglas L. Cunningham, DO: My professional belief is that there are three key considerations when selecting treatment options for virologically suppressed patients looking to switch their current regimen. First, does this regimen have a high genetic barrier to resistance? If my patient is experienced on therapy, how can I select a regimen where the presence of resistance may not be an issue? Second, if my patient is switching due to tolerability concerns, what are the most common adverse reactions associated with the different treatments? Does this regimen have a low discontinuation rate? and lastly, is this available as a single-tablet regimen? With all of the treatment options we now have available, individualization of therapy is key. We need to take into consideration the clinical and social factors of a patient before selecting a treatment option, and in order to make an informed decision, we need to understand the evidence behind these treatments.
Dr. Douglas L. Cunningham, DO: One of the latest treatment options we can consider for virologically suppressed patients who are looking to change therapies is SYMTUZA®, the first and only protease inhibitor-based single tablet regimen. SYMTUZA® is indicated as a complete regimen for the treatment of HIV-1 in adults who are treatment-naïve or appropriate virologically suppressed patients. The Boxed Warning for SYMTUZA® is tied to post treatment exacerbation of hepatitis B in patients co-infected with hepatitis B and HIV-1, which may occur when products containing emtricitabine and/or tenofovir, such as SYMTUZA®, are discontinued. These patients should be monitored very closely for several months following discontinuation of SYMTUZA®.
Dr. Douglas L. Cunningham, DO: Recently, I was an investigator in the EMERALD study, a clinical trial of virologically suppressed patients who were switched to SYMTUZA®. This is one of the pivotal trials that led to the FDA approval of SYMTUZA®. I was excited to participate in this study, because it represented a potential advancement in care for my patients living with HIV.
Dr. Douglas L. Cunningham, DO: EMERALD was a Phase 3 randomized, open-label, non-inferiority study comparing the efficacy of SYMTUZA® to a boosted protease inhibitor plus Truvada®. Patients were virologically suppressed on a boosted PI plus Truvada for at least six months with no prior virologic failure on darunavir or known darunavir RAMs. Patients were randomized two to one to either switch to SYMTUZA® or continue their current regimen for 48 weeks.
Dr. Douglas L. Cunningham, DO: One distinguishing feature is that the presence of emtricitabine or tenofovir RAMs was not an exclusion criteria of the EMERALD study. So, for example, patients were allowed to participate in the study if they had the M184V mutation. This is a key attribute of the study based on the prevalence of the M184V mutation and overall emtricitabine resistance in HIV patients. Another important aspect of the inclusion criteria is that prior virologic failure on a regimen was allowed, which is a factor that often excludes patients from other clinical trials. After week 48, patients who were randomized to switch to SYMTUZA® were given the option to continue treatment and were followed out to week 96. Patients who were initially randomized to stay on their boosted PI plus Truvada® were also given the option to switch to SYMTUZA® after 48 weeks and to be followed to week 96. The primary endpoint of the study was the proportion of patients with virologic rebound at week 48 with a non-inferiority margin of 4%. A key secondary endpoint was to measure of the proportion of patients who had a viral load of less than 50 copies per mL at the 48 weeks using the FDA snapshot analysis.
Dr. Douglas L. Cunningham, DO: The demographics of the EMERALD study were generally similar across both arms, and the age range is consistent with what I see in patients switching treatment in my practice, many of whom have faced previous challenges related to treatment.
Dr. Douglas L. Cunningham, DO: In the study, a larger percentage of patients had prior experience with at least five ARVs, and prior treatment regimens were diverse, including experience with integrase, NNRTI, and PI-based regimens. Also, of note, 15% of the patients in the study had prior virologic failure on other regimens.
Patient: Now I’m taking SYMTUZA® so it’s only one pill, which is way more convenient, as far as my day to day life. I was kind of nervous when they approached me to be part of the EMERALD trial, possibly having to take new medication and possible side effects, that’s one thing I was kind of scared of.
Dr. Douglas L. Cunningham, DO: Tolerability is one of my primary concerns when choosing a treatment, especially when switching a virologically suppressed patient. I think many providers may be thinking of the various misconceptions that are out there about darunavir or from the old days of protease inhibitors. I think the main thing patients or providers worry about is GI side effects. Let’s review tolerability data for SYMTUZA® reported in the study.
Dr. Douglas L. Cunningham, DO: During treatment, 1% of patients discontinued SYMTUZA® due to adverse events at week 48, and most adverse events were mild to moderate in severity. There were no treatment-related discontinuations due to insomnia, anxiety, or weight gain over 48 weeks in either arm of the study. Three percent of patients in the SYMTUZA® arm and 2% in the control arm started a lipid-lowering medication by week 48. Though there were no new cases of Type 2 diabetes with SYMTUZA®, new onset and exacerbations of diabetes mellitus and hyperglycemia have been reported with PIs as a class. So, it’s important to monitor patients who are at risk.
Dr. Douglas L. Cunningham, DO: The most common treatment-related adverse events over 48 weeks in the EMERALD trial were diarrhea and osteopenia with an incidence of 2% and 1% respectively. Only one patient or 0.1% of the patients from the study discontinued due to diarrhea. Most adverse events in the study were mild to moderate, grades 1 and 2. So, what does this mean? This tells me that SYMTUZA® is very well tolerated and has low GI side effects.
Dr. Douglas L. Cunningham, DO: Looking at the efficacy of SYMTUZA®, we see that at 48 weeks, 95% of patients on SYMTUZA® were undetectable. Rates of virologic failure were 1% in both the SYMTUZA® arm and the control arm at 48 weeks. Four percent of patients in the SYMTUZA® arm had no virologic data available versus 6% in the control arm at 48 weeks.
Dr. Douglas L. Cunningham, DO: Patients in the EMERALD study faced real-world treatment challenges, and their inclusion is part of what makes this study and the results of SYMTUZA® important. In the study, 15% of patients had previous virologic failure including failure on an integrase inhibitor, NNRTI, or PI. This did not impact treatment outcomes. As a reminder, the indication for SYMTUZA® is distinct from among STRs approved for virologically suppressed patients looking to switch treatment regimens, because SYMTUZA® is the only STR containing emtricitabine and TAF that does not require patients to have susceptibility to emtricitabine. Fifty-three patients across both treatment arms had archived emtricitabine-resistance associated substitutions, mainly M184. One hundred percent of these patients maintained virologic suppression at 48 weeks.
Dr. Douglas L. Cunningham, DO: With the protective barrier of SYMTUZA®, zero treatment-emergent mutations occurred in patients studied in the EMERALD trial. This is consistent with what I’ve seen with darunavir.
Dr. Douglas L. Cunningham, DO: In fact, over 5500 patients have been treated with darunavir in 14 clinical trials with long-term data up to 192 weeks, and there has been no increase in darunavir-resistance associated mutations over ten years.
Dr. Douglas L. Cunningham, DO: The DHHS guidelines recommend darunavir-based regimens like SYMTUZA® in situations where patients may be at risk for developing resistance, such as those with suboptimal adherence.
Patient: I have been on SYMTUZA® I think it’s been two years, maybe two and a half now. I see the doctor every three months to draw my blood and to go over my numbers, making sure everything is still good, still undetectable. To me it means to be undetectable by being healthy. They’re like your viral load is undetectable. I was thinking like, oh okay, that’s great news. I like as long as it’s undetectable, then my body is still working normally.
Dr. Douglas L. Cunningham, DO: What you see with SYMTUZA® is an ARV where resistance protection meets tolerability. This makes it an attractive option in my toolbox for virologically suppressed patients who are ready to change treatment. As clinicians, we know that patients aren’t always aware of the options that may be available to them. So, it’s important that you, the healthcare provider, discuss potential issues with your patients, and if they are on a multi-tablet regimen, evaluate if a single-tablet regimen like SYMTUZA® is right for them. As providers we have our patients’ interest at the core of any decision we make. Based on the data we have reviewed today, I would encourage you to review the factors you take into consideration when initiating a treatment switch and ask yourself these two questions.
Dr. Douglas L. Cunningham, DO: First, do you have patients on PREZCOBIX® or PREZISTA® 800 mg who could benefit from simplifying their regimen to once-daily SYMTUZA®?
Dr. Douglas L. Cunningham, DO: And second, beyond those patients, do you think SYMTUZA® may be a potential treatment option for those virologically suppressed patients not tolerating their current regimen?
Dr. Douglas L. Cunningham, DO: Let’s review some of the Important Safety Information about the contraindications for SYMTUZA®.
Dr. Douglas L. Cunningham, DO: Before starting treatment with any medication, it’s important to understand and assess the patient and the potential for drugs and the contraindications. SYMTUZA® should not be administered with the drugs on this list due to the serious and/or life-threatening events or loss of therapeutic effect. Please take a moment to read.
Dr. Douglas L. Cunningham, DO: Some warnings and precautions for SYMTUZA® include hepatotoxicity. Drug-induced hepatitis and cases of liver injury including some fatalities have been reported in patients receiving darunavir. You should monitor liver function prior to initiating and during therapy and consider discontinuing SYMTUZA® in patients with new or worsening liver function.
Dr. Douglas L. Cunningham, DO: Severe skin reactions may also occur. Discontinue SYMTUZA® immediately if signs or symptoms of severe skin reactions develop. Please ensure you consult the full Prescribing Information prior to and during treatment, as the risk of serious adverse reactions or loss of virologic response due to drug interactions may occur.
Dr. Douglas L. Cunningham, DO: Additional Warnings and Precautions include onset or exacerbations of immune reconstitution syndrome. New or worsening of renal impairment may occur. SYMTUZA® is not recommended in patients with creatinine clearance below 30 mL per minute. Prior to or during treatment on a clinically appropriate schedule, monitor serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Discontinue SYMTUZA® in patients who develop clinically significant decreases in renal function or evidence of Fanconi’s syndrome.
Dr. Douglas L. Cunningham, DO: Darunavir contains a sulfonamide moiety. The incidence and severity of rash were similar in subjects with or without a history of sulfonamide allergy. Monitor patients with a known sulfonamide allergy. Lactic acidosis and severe hepatomegaly with steatosis including fatal cases have been reported with the use of emtricitabine and TDF. Discontinue SYMTUZA® in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.
Dr. Douglas L. Cunningham, DO: Though there were no new cases of Type 2 diabetes with SYMTUZA®, new onset and exacerbations of diabetes mellitus and hyperglycemia have been reported with PIs as a class. So, it’s important to monitor patients who are at risk. Fat redistribution may occur in patients receiving ART, and increased bleeding may occur in patients with hemophilia.
Dr. Douglas L. Cunningham, DO: It is important to note that in treatment-naïve patients, the most common clinical adverse reactions all grades occurring in at least 2% of patients were diarrhea, rash, nausea, fatigue, headache, abdominal discomfort, and flatulence. This is not a complete list of all adverse drug reactions reported with the use of SYMTUZA®. Overall, the safety profile of SYMTUZA® in virologically suppressed adults was similar to that in naïve subjects who were treated with SYMTUZA®. Please refer to the full Prescribing Information for a complete list of the adverse drug reactions.
Dr. Douglas L. Cunningham, DO: And here is information on use in special populations including pregnancy and lactation. Consult the full Prescribing Information for SYMTUZA® for additional information on the Uses in Specific Populations.
Dr. Douglas L. Cunningham, DO: Thank you for watching. To learn more about SYMTUZA®, talk to your Janssen representative.