Stream this podcast to learn from experts Alexis E. Horace, PharmD, BCACP, and Nimish Patel, PharmD, PhD, AAHIVP, how specialist pharmacists can overcome key barriers to care and apply best practices for optimization of antiretroviral therapy for HIV.
Stream this podcast to learn from experts Alexis E. Horace, PharmD, BCACP,andNimish Patel, PharmD, PhD, AAHIVP, how specialist pharmacists can overcome key barriers to care and apply best practices for optimization of antiretroviral therapy for HIV. Topics covered include:
Presenters:
Alexis E. Horace, PharmD, BCACP
Professor of Pharmacy Practice
University of Louisiana at Monroe College of Pharmacy
New Orleans Campus
CrescentCare Ambulatory Care Clinical Pharmacist, HIV Specialty
New Orleans, Louisiana
Nimish Patel, PharmD, PhD, AAHIVP
Professor of Clinical Pharmacy
Division of Clinical Pharmacy
Skaggs School of Pharmacy & Pharmaceutical Sciences
University of California, San Diego
La Jolla, California
Link to full program:
https://bit.ly/41agtqQ
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This transcript was automatically generated from the audio recording and may contain inaccuracies, including errors or typographical mistakes.
Dr. Alexis E. Horace (University of Louisiana): My name is Alexis Horace, and I'm a Professor of Pharmacy Practice with the University of Louisiana at Monroe College of Pharmacy. I'm also the Ambulatory Care Clinical Pharmacist for Crescent Care, where I have an HIV specialty.
Dr. Nimish Patel (University of California): Hello, everyone, and thank you for joining. My name is Nimish Patel. I'm a full professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California, San Diego, and I maintain a clinical practice site in investigational drug pharmacy at a site called the Antiviral Drug Research Center.
Dr. Horace: So, I'm very excited to be here today to talk about how we can leverage pharmacists' expertise in helping to treat patients living with HIV.
2023 HIV Diagnoses in US, 6 Territories, and Freely Associated States
So, looking at our data from 2023 HIV diagnoses, we can see that there were approximately 40,000 individuals who were newly diagnosed during that time at a total rate of 13.7. The majority of these diagnoses occurred in the southern region, as well as Illinois, California, and Nevada.
2023 HIV Prevalence by Select Characteristics in US, 6 Territories, and Freely Associated States
When we look at the characteristics of these individuals during this time, we can see that the primary sex identified at birth is male, and nearly one half million were aged 55 or older. I always find it interesting that we have this perception that it's a younger generation or younger individuals who are being diagnosed, but we can see that we have the majority starting at 35, going all the way up to 75 years old. And then looking at race and ethnicity, we have African Americans as well as Hispanics and Latinos that are the – the major races.
Landscape of ART: Classes
The landscape of antiretroviral therapy has changed greatly over the years and for the better. And we now have nine classes of antiretroviral therapy, which can be overwhelming. And so today, we are not going to get into the details of each of these classes and the plethora of medications that belong in them. But you can review those on your own time. But I will just quickly go through some quick information about where these medications work.
So, we have our nucleotide/nucleoside reverse transcriptase inhibitors, and our nonnucleoside, reverse transcriptase inhibitors. And these medications work on inhibiting reverse transcriptase for making viral RNA in the CD4 cell. Then we have our protease inhibitors which work on the back end, decreasing protein synthesis and repackaging of the viral HIV. We have our integrase strand transfer inhibitors. And these prevent the viral RNA from incorporating itself into the host cell DNA in the CD4 cell in the nucleus.
Next, we have our fusion inhibitor, CCR5 antagonist, and then our CD4 cell post-attachment inhibitors. And so these medications prevent HIV's entry into the CD4 cell. And then finally, we have some of our newer agents like our Gp120 attachment inhibitors and our capsid inhibitors, which are really cool because they actually attach to the HIV virus itself and prevent it from attaching to the CD4 cell.
DHHS, IAS-USA Guidelines: Recommended First-line ART Regimens for Most People Living With HIV
When looking at our guidelines for first-line therapies of choice, it's been very simplified, which is great for new practitioners especially. So, if you have a patient who has never previously used cabotegravir for pre-exposure prophylaxis, that's what PrEP stands for, then we definitely want to start with some of our newer agents like bictegravir with emtricitabine and tenofovir alafenamide. And then we also have other options with dolutegravir with emtricitabine and lamivudine, and – well, plus tenofovir alafenamide and tenofovir disoproxil fumarate. And just so I don't get tripped up today, if I say TAF and TDF, that's what I mean by those two abbreviations.
And then we have dolutegravir and lamivudine, which is a two-drug medication or a two-drug combo, which is really cool because we are decreasing the amount of medications that they're taking. And so these are great for individuals who have a viral load of less than 500,000 copies, they have no HBV co-infection, and they also have some resistance testing results to show that they don't have any integrase inhibitor resistance, which is that dolutegravir. We'll also talk a little bit later about why a person should not have HBV for this medication.
If you have a patient who previously used cabotegravir as PrEP, then we definitely want to make sure that we are performing INSTI resistance testing beforehand, so genotype testing, to make sure that we don't have any resistance for that integrase inhibitor. But if it is necessary or part of the shared decision-making model with that patient that you want to start therapy that day and your results are pending, then the guidelines say that, sure, you can start a darunavir-boosted regimen, boost it with cobicistat or ritonavir, and then add that to emtricitabine or lamivudine plus TAF or TDF.
ART Landscape for Regimen Simplification
I've always been fascinated with how easy regimens have gotten for our patients, and I'm so thankful for the simplification and how that's become one of the goals for creating therapies for patients. And so now we have single-tablet regimens that have two to four medications coformulated into a single tablet.
And even more exciting is that when I started this practice many years ago, I would have never imagined having a long-acting agent where a person can take something monthly or bimonthly. It always just seemed like it was this fantasy and it's actually here. So, we have cabotegravir plus rilpivirine, and there are two separate injections that can be given monthly or bi-monthly. And if a person has an undetectable viral load, we can switch them to these medications if it suits their lifestyle.
Just as a side note, there is another long acting antiretroviral agent called lenacapavir that can be given every six months for treatment-experienced patients. So, these are patients that have – have – they have been heavily treated for their – well, for their HIV with antiretrovirals. And they have some forms of viral resistance to some of the drug classes we talked about previously. But even more exciting is that you may have seen in the news recently, over this summer, that lenacapavir has been approved for PrEP treatment in people without HIV.
Goals of Therapy
The goals of therapy for treatment include maximally and durably suppressing plasma HIV-1 RNA, restoring and preserving immunologic function, reducing HIV-associated morbidity and prolongation while prolonging the duration and quality of survival, and to prevent HIV transmission.
Pharmacist Roles in HIV Care and Management
So, what are the roles of pharmacists in the care for patients living with HIV? I'm not going to labor this slide too much, but there's so much that we can do within this profession for our patients. And this is all the way from disease state education, adherence counseling, increasing access to care, selecting appropriate ART optimization, which we will talk about, antiretroviral stewardship, which is something that I started off within residency, and then something that I really care about and that I do for my current practice, which deals with medication de-escalation and/or simplification.
And as we spoke about earlier in some of the previous slides with our older population becoming newly diagnosed, and then also people living with HIV having longer lifespans, the opportunities for the development of comorbid disease states has increased. And along with those comorbid disease states comes all the medications to treat those disease states. So, oftentimes, I get pulled into a care model or a care plan to help manage many medications in polypharmacy.
Advocate for ART
One of the roles that we can also play as pharmacists is to advocate for ART, especially for starting ART as soon as possible. There is an INSIGHT START trial which found that there was a 57% reduction in risk of serious AIDS-related events, serious non-AIDS-related events, or death from any cause when we started ART as soon as possible versus those who deferred treatment.
Shared Decision-making: Results From 2019 Positive Perspectives Survey
But why does this not happen, or especially if we start a patient on antiretroviral therapy, why do they not sustain that treatment? So, there was a study that looked at shared decision-making, and they found that among 2,389 individuals living with HIV across 25 countries, 65.1% wanted more involvement in their decisions about their HIV treatment. And among those, 28.9% indicated that their HIV medications limit their lives.
I think as pharmacists, we can play a huge role in communicating and sharing in the decision-making with patients to help improve these opportunities, so that way their medications are not limiting their lives. Also, of this group, 203 did not discuss their concerns with their health care provider.
So, some of the actual barriers that were identified included that they did not believe their healthcare provider could do much to help them, or maybe their health care providers never bring it up, so what's the point? And maybe it's not such a big deal. Or how do they bring it up? And some people said they didn't want to come across as a difficult patient, which is something that I've dealt with as well. And I have many patients who come wanting to please me and wanting to please a provider, but when I dig deeper, I find that sometimes they're just not happy with their medication regimens. And then also, some patients feel like there's not enough time for them. Maybe their appointment slots are too short, or they feel rushed and they don't get answers to some of the questions that they have. So, in my role as a pharmacist for my clinic, I find that I have just a little bit more time that I can spend with patients so that way I can bridge that gap and try to find more information to help that patient feel more at ease.
Patient-Specific Factors for Consideration
So, let's start thinking about some of the patient-specific factors that we can consider as pharmacists when we are working with patients living with HIV.
Assessing Patient ART Preferences
One of the first things that I like to do, especially when I get a newly diagnosed person or even someone who's treatment-experienced and they have a ton of medications, I look at their pill burden. What are they already taking? How many pills are they taking? What pill sizes do they have? Some of our single-tablet regimens are pretty hefty. They are vitamin-sized tablets and not everyone can swallow those. And then dosing frequency. If you have someone who has a very regimented lifestyle, then maybe a daily single-tablet regimen works for them. But if you have someone who has less of a schedule, who's flying by the seat of their pants, and maybe they might need something that's more lenient to their lifestyle.
And then also, we need to consider the potential side effects. When thinking about disclosure and privacy concerns, it's important to ask patients, "Have you disclosed your status to the people that you live with?" With all the mail-in pharmacies, is it safe to mail medications to your home? Can something be delivered to your front step? So, really thinking about these privacy concerns and coming up with the options that are best for this patient.
And then there's adherence history and lifestyle factors that also influence medication regimens. If a person is not adherent to their appointments and they're missing their labs, then perhaps certain regimens might not be the best for them.
So, our role as a pharmacist is to counsel on options, support adherence, and then also participate in shared decision-making with our patients. As I said before, we have over nine classes of medications, all types of simplified regimens. Surely, there is something that can work for a patient in treating their HIV. And then we also need to make it a routine part of every visit to discuss whether the person is on the best regimen for them.
[00:37:08]
Pharmacist Participation in ART Initiation Can Improve Treatment Outcomes
So, there was a study that was done with pharmacist participation in ART initiation, and it was a retrospective cohort analysis where they compared outcomes among individuals with new HIV diagnosis before 2017 versus those after in 2019, and the cohort in 2019 worked with pharmacists in a pharmacist-driven rapid ART treatment arm. And what they found is that there was a shorter median time to viral suppression in the pharmacy rapid ART arm versus pre-implementation, and this was 30 months versus 66 months. Also, they found a significantly higher likelihood of viral suppression at any time during that study.
Other outcomes for the PHARM-D arm included a 94.1% retention in patients at one year, and 98% remained virally suppressed at last viral load measure.
So, this study is really exciting to me, and even though it's a little bit older, it shows that we as pharmacists can make a huge impact in starting patients on antiretroviral therapy, but more importantly, retaining people in care.
People With HIV May Experience a Variety of Health-Related Needs, Especially Older Individuals
As we spoke about earlier, we have many older individuals who are living with HIV. And so along with that comes with many comorbid disease states like cardiovascular disease, renal disease, liver disease, hyperlipidemia. And one of the biggest things is polypharmacy because most of these disease states have to be treated with medications. And typically it's not just one medication. It's going to be a variety of medications for each of these disease states. So, what are some of the considerations that we should think about when we are treating these patients?
ART Management With Renal Impairment
We'll start with renal impairment. And as pharmacists, one of the things that's drilled into us in pharmacy school is to check for renal function and appropriately renal-adjusting medications. So, one of the things that I do with every patient is I calculate a creatinine clearance and I check their renal function to renally dose them.
So, talking about TDF, if you have a person who has a creatinine clearance of less than 50 ml/min, you want to adjust the dose. If someone is on TAF and they're creatinine clearance is less than 15 ml/min, it is recommended not to prescribe this medication anymore. However, if this person is switched to hemodialysis, you can then continue this medication without dose adjustments and just dose it after the days that person has hemodialysis.
If a person is on lamivudine and their creatinine clearance is less than 30 ml/min, it's recommended to adjust the dose. And if you have someone who is on emtricitabine, it's the same as lamivudine. However, if that person is on chronic hemodialysis, you can continue the same dose and just give the dose after dialysis. Bictegravir with emtricitabine and tenofovir alafenamide also needs to be renally adjusted. Bictegravir with emtricitabine and tenofovir alafenamide comes as a single-tablet regimen, only it doesn't come in at separate components. And because of that we need to dose it for this emtricitabine. There are other medications that do not need the dose adjustments, like dolutegravir, cabotegravir plus rilpivirine. And if you have a person who is started on hemodialysis or they are starting to have kidney problems, then we need to just monitor them for adverse effects.
[00:41:31]
ART Management With Hepatic Impairment
When looking at hepatic impairment, if we have individuals who are on darunavir, which is what DRV stands for, it is not recommended for patients with severe hepatic impairment. And then for those that are on TAF, which is tenofovir alafenamide, if they have a Child-Pugh class score of B or C, this medication is not recommended. Then, for a dolutegravir, bictegravir with emtricitabine and tenofovir alafenamide, and cabotegravir plus rilpivirine, if a person has a Child-Pugh class of C, these medications are not recommended.
So, it's important to calculate Child-Pugh classes for patients just to ensure that we are dosing medications appropriately. There are some medications that do not need adjustments, like lamivudine, or tenofovir disoproxil fumarate.
ART Management With HBV Coinfection
Now I would like to talk a little bit about antiretroviral therapy management with patients living with HBV.
So, we brought this up at the beginning as well when we talked about dolutegravir with lamivudine. There are some medications that we use to treat both HIV and HBV, and therefore if you stop an antiretroviral therapy regimen, you may have an exacerbation of that person's HBV because those medications are treating both. Additionally, when a person is living with HBV, you don't want to just use monotherapy. And so, emtricitabine and lamivudine are agents that are used to treat HBV. And they should not be used alone. So, with dolutegravir and lamivudine, the lamivudine is by itself. So, therefore, the HBV can become resistant to that lamivudine and develop viral resistance. So, we always want to make sure that we are pairing emtricitabine and lamivudine with a TDF or TAF counterpart.
Cardiovascular Disease in People Living With HIV: Statin Therapy Recommendations
For the longest time, we knew that HIV affected people living with cardiovascular disease differently. We – we always assume that HIV had some effect on patients. We just didn't have the data to support it, or we didn't have the guidelines to support starting someone on a statin. And so the guidelines have been updated, and they fully support the use of statin therapy in patients living with HIV.
Patients who are living with HIV are at twofold times higher risk of ASCVD. So, for a patient who is living with HIV, and their ASCVD risk score is 5% but less than 20%, the guidelines recommend initiating a moderate intensity statin with a strong recommendation. And if this person has an ASCVD risk score of less than 5%, there is favor for initiating a moderate intensity statin, but the benefits are modest. And so this is when it's time, once again, to enter into this shared decision-making model with the patient to see if a statin therapy is the best fit for them. And you would also want to look at their HIV-related ASCVD risk factors, which can include long duration of HIV infection, extended periods of viremia, maybe they've had non-adherence or low CD4 cell counts for a long time.
However, if you have anyone living with HIV or not living with HIV and they have an ASCVD risk score of greater than 20%, we recommend starting a high-intensity statin. And if you have anyone who's living with diabetes, then it's recommended that we start a moderate-intensity statin in these patients, and considering their diabetes risk, you may want to start a high-intensity statin.
And then anyone, regardless of their ASCVD risk score, if they have an LDL of greater than 190, which is indicative of perhaps a genetic disorder with their cholesterol, they should be initiated on a high-intensity statin at the maximum tolerated dose.
So, with that being said, I'm going to go ahead and pass it on to Dr. Patel, who's going to start off with drug-drug interactions.
ART Management With Comorbidities: Additional Recommendations and Considerations
Dr. Patel: Thank you for that, Doctor Horace. So, you know, just to kind of close out the conversation that Dr. Horace had started with cardiovascular disease, when looking at antiretroviral therapy and management with individuals with different comorbidities, certainly in individuals with cardiovascular disease, there are some agents where there are data to suggest that we may want to avoid them.
So, there have been a number of studies with differing results that point to abacavir as well as darunavir to avoid them in individuals with cardiovascular disease. And, you know, the nice thing about the landscape of antiretroviral therapy these days is we have a lot of options. We know that TDF has effects on bone mineral density, especially in individuals who are using TDF for prolonged periods of time. While not used frequently in individuals with mental health diagnoses, there are some CNS adverse effects that can be experienced with efavirenz. And with some of the older protease inhibitors, we do have concerns about some PIs affecting lipids and then to avoid cobicistat in individuals who are pregnant.
Addressing DDIs: ART and Concomitant Medications
So, let's talk about drug-drug interactions with ART and concomitant medications that people are using to treat their other comorbid conditions.
So, pharmacists are uniquely poised to see all the medications that an individual may be using, especially when people are receiving care from different providers in different institutions. So, pharmacists certainly have the ability to perform medication reconciliation and manage drug-drug interactions that exist between ARVs and other medications that are used for other comorbid conditions. And ideally pharmacists should be doing this type of review on a regular basis, especially when new ART regimens are initiated or another concomitant medication is started.
Drug-drug interactions are sometimes difficult to predict when you have multiple drugs that are going through the same metabolic pathway, and, you know, there are some common interactions that pharmacists can be involved in. And I think this first one can be concerning because antacids are so readily available over the counter. So, antacids reduce the absorption of integrase inhibitors, so it's certainly something to tell patients even if they don't have anything in their medication profile. Rifampin can affect the concentrations of several antiretrovirals, and by having a reduced concentration of those antiretrovirals that can affect whether or not those antiretrovirals can achieve an undetectable viral load, which is the primary goal of HIV therapy. There are interactions that are usually manageable with statins. PPIs can be problematic, particularly for rilpivirine, and many anti-epileptic or anticonvulsants have interactions that should be considered. It's always good to ask about herbal supplements and OTC products just to ensure that there isn't an interaction that could affect ART effectiveness.
Polypharmacy
So, I'm going to talk about polypharmacy, which certainly is a big driver of drug-drug interactions. And within the literature a number of different definitions are used. But I think a frequently used one is the use of at least five medications. And using multiple medications. or polypharmacy, certainly is associated with reduced adherence and increased risk of adverse events, and geriatric syndromes such as falls. There's also data that is related to mortality, and the risk of mortality is proportional or goes up in a dose response way with the number of medications that are used. So, as more and more medications are used, the risk of all-cause and cardiovascular disease mortality goes up simultaneously.
General Deprescribing
What I'm also going to talk about is general deprescribing. So, this really can be broken up into two different buckets in dealing with individuals who have HIV. So, there's the deprescribing that's associated with the ART regimen and there's deprescribing associated with non-ART regimens. So for individuals who are on these legacy regimens that have a high pill burden or associated with a number of toxicities, it may be an opportunity to change the regimen to something that is associated with a lower pill burden, fewer drug interactions, and fewer adverse effects while maintaining an undetectable viral load.
For non-ART medications, you know, as a pharmacist, you certainly see medications that are continued inappropriately. And it's an opportunity for pharmacists to pull those medications off the profile. And then for medications where patients have achieved their goals, it may be an opportunity to reduce the dose or switch the medication altogether. So, I mean, I think with any type of prescribing, it should be done under the supervision of the patient's prescribing physician as well as in concert with the pharmacist.
POPPY Study: Polypharmacy and DDIs in Older and Younger People Living With HIV
I want to just talk about a study that was done looking at polypharmacy and drug interactions in older and younger individuals with HIV, and then a comparator cohort of individuals who were older than the age of 50 but did not have HIV. Individuals who are older with HIV have a higher percentage of drug-drug interactions than individuals who are less than the age of 50. And that makes sense. Typically, there's a lot of age-related comorbidities that one acquires after the age of 50. But what was really unique was when you compared these individuals to their non-HIV counterparts who are in the same age bracket, there's also a significant difference in drug-drug interactions between non-ARV drugs. And you can kind of see that visually displayed here in the table. Those who are above the age of 50, and less than the age of 50, there are differences in where there are drug-drug interactions that are observed.
ART Management for Treatment-Experienced Patients
So, when managing treatment-experienced patients, this certainly can be a challenging situation for pharmacists and clinicians in general. But the general approach is similar to that of treatment naive individuals. So, trying to understand the reason for switch is, you know, there – is it because they're on a legacy regimen with a lot of pills, and you want to reduce the pill burden so that they are more likely to be adherent? Is that a toxicity thing? What is the viral load at the time of switch? There are some regimens that are more conducive for switching when the viral load is undetectable versus some regimens where the viral load is – the regimen is more conducive when the viral load is detectable.
Underlying resistance is a huge consideration because this will drive what agents you can have in the new regimen. And understanding a person's previous ART regimens will help understand what you can select for future regimens, as they may have acquired resistance over time.
Concomitant medications are important for drug-drug interactions. And Dr. Horace talked about shared decision-making. It's really important to understand what are the key factors that are important to the patient, because by optimizing those key factors, the patient is more likely to take the medication and remain adherent to the medication.
[00:57:55]
Treatment-Experienced Patients
So, one scenario that happens when managing persons with HIV who are treatment-experienced is the issue of persistently low CD4 cell counts. So, persistently – so this is language directly from the DHHS guidelines. "Persistently low CD4 cell counts and increased immune activation are each associated with increased AIDS and non-AIDS related morbidity and mortality among individuals with ART mediated viral suppression."
So, in those individuals who are suppressed but their CD4 count is still low, the general dogma is switching regimens or adding new agents is actually not recommended. That CD4 count over time, provided the virus is suppressed, will on its own come up. It just may take a while to get there. But really, there are a number of other factors that can affect CD4 count, and efforts to impact morbidity and mortality should really focus on these modifiable factors. So, smoking in and of itself can depress a CD4 count. So, encouraging individuals to participate in smoking cessation, a healthy diet, getting enough sleep can also be impactful, exercise to reduce that cardiovascular risk, treating hypertension and dyslipidemia.
Considerations When Switching Regimens in Patients With Viral Suppression
Okay. So, when switching regimens in people who do have urologic suppression, there's a number of things that should be considered.
So, I'll start with drug resistance. And it's important to review a patient's entire antiretroviral treatment history, especially if they failed regimens in the past, because that may determine whether or not they have some underlying resistance to those agents that were in some of their previous regimens. If available, looking at all resistance tests, because the mutations that appear on a genotype are just the ones that are – the ones that are predominant. So, some of the regimens may archive themselves and may not be the ones that are predominant at the time of the genotype.
If there's no history of resistance or virologic failure, switching to any regimen highly effective – is a highly effective strategy. And, you know, there's a number of different options that are available, including two-drug regimens, such as long-acting cabotegravir and rilpivirine or dolutegravir and rilpivirine. Okay. So, for individuals with pre-existing NRTI resistance, if the new regimen includes NRTI, ideally, you'd want to include two NRTIs plus a fully active drug with a high barrier to resistance, such as dolutegravir, bictegravir, or boosted darunavir.
If the goal is to use a NRTI -sparing regimen, dolutegravir rilpivirine is certainly something that's been used as well as long-acting cabotegravir rilpivirine provided that there's no evidence of previous INSTI or rilpivirine resistance. When you have resistance to multiple classes, oftentimes this is kind of the point to dial it in and consult an ID physician who has experience with treating patients who have multi-class resistance.
Other considerations include safety and selecting regimens that have a fairly favorable adverse effect profile for the patient, as well as looking at their concomitant medications and seeing which concomitant medications are compatible with the regimen that you're selecting. We know that some of the regimens are affected by the presence of hepatitis B co-infection and pregnancy, and making sure that the regimen is optimized to ensure that either hep B coinfection or pregnancy are adequately managed.
And then monitoring, ideally, we'd want to monitor for tolerability, but the goal of antiretroviral therapy is virologic suppression. And the way that people get there is by being adherent to their medications. And generally, we would monitor about three months after a switch.
Recommendations for Management of Multidrug-Resistant HIV
Okay. So, just some, you know, brief recommendations for the management of multi-drug resistant HIV. If you don't have a fully active boosted PI or second-generation INSTI, you may need to piecemeal a regiment together of – with – you know, two preferably three fully active drugs. And this is where you're going to look at the phenotype. So, the genotype gives you the drug mutations, the phenotype gives you the degree of drug resistance. And with that, you'll be pulling together multiple drugs to give you the activity of three fully active drugs. And you may need to dip into some of the novel drugs that have been approved in the treatment experience space.
Integration of Gender-Affirming Therapy and HIV Care
And then I just want to close off the presentation by talking about gender-affirming therapy and HIV care. So, guidelines for gender-affirming hormone therapy generally provide a standardized approach. And there may be other comorbidities that you have to consider when affecting or changing the GAHT. The lab monitoring for GAHT follows a similar schedule to that of HIV labs, and you're typically drawing labs every three months. And this is a great opportunity for pharmacists to aid in the pharmacotherapy for not only antiretroviral therapy, but also for gender affirming therapy.
Patient Concerns
Many individuals who are transgender have concerns about drug-drug interactions and their – between their GAHT and their ART. And a number of people will actually prioritize their GAHT over their ART due to concerns with drug-drug interactions, and less than fewer than – less than half of people are willing to talk about this concern with their health care provider.
[01:06:42]
Gender-Affirming Hormone Therapy: Potential Interactions Do Not Prohibit ART
So, it's important to be proactive and counsel patients that the impact of GAHT on ART concentrations, there's generally no clinical significance. And the impact of ART on gender-affirming hormonal therapy, it's generally theoretical and likely has no clinical significance. In terms of drug classes, the INSTIs are have the lowest potential to affect GAHT and no adjustments are typically necessary. But the nice thing about GAHT is you can titrate GAHT doses based on the clinical effects and the hormone concentrations. For PIs, and PIs are certainly used less frequently than INSTIs, there isn't as much data, but the impact is not necessarily clear whether or not PIs increase or decrease GAHT concentrations. But fortunately, we are able to monitor hormone concentrations and titrate GAHT doses based on those concentrations and changes in clinical effects that may occur.
ART Adherence Considerations With GAHT: Monitor Clinical Effects and Hormone Levels
So, you know, adherence can be a concern among transgender persons using GAHT, and I think it's just an opportunity as a pharmacist to continually have that conversation and engage patients in informative discussions about how there's unlikely a meaningful impact on ART on GAHT, and that reduced adherence to ARVs is actually more harmful. Hormone levels are being monitored roughly at the same interval as HIV labs, and it's an opportunity to review those and just visually show patients that things aren't changing. And finally, just reassure patients that once estradiol levels are in physiologic range, increasing the levels does not necessarily associate with an increased effect, but rather it can increase the risk of adverse effects.
So, with that, that concludes our presentation. And Dr. Horace and I will take some questions.
Q&A
Dr. Horace: I see some in the chat. So, one of the first questions is though not generally used alone, is the risk of hepatitis B resistance development high for TDF or TAF, or is it just for FTC and 3TC? TDF and TAF have a higher barrier to resistance, and so with emtricitabine and rilpivirine having a low barrier to resistance, I think that's why we want to pair it with TDF or TAF, for those reasons.
Do you have any other feedback, Dr. Patel?
Dr. Patel: No. I agree with that. And I mean, the other consideration is just discontinuing regimens that contain TDF or TAF or 3TC and FTC because that can also run the risk of a hepatic flare. So, I'm just going to go through some of the other questions in the chat box. What is – what is your opinion on continuing photosensitivity in patients with a creatinine clearance between 30 and 50 who wished to remain on fixed dose single tablet regimens formulated with dolutegravir or bictegravir? So, this is the tough one because there – the product label does recommend a dose adjustment. And usually when you have to adjust the dose, you need to split up the products. There's not really a good answer for whether to continue – continue or not. I don't think we have enough safety data on the consequences of having an NRTI accumulate in those individuals who have reduced creatinine clearance. So, I think the jury is still out on that one. Dr. Horace?
Dr. Horace: Yeah. I think for me, it's – it's really a risk versus benefit for the patient. And when we are looking at the clearance of emtricitabine and lamivudine, it's really just about accumulation. And they have a really clean side effect profile as well. And so, if a patient is adherent to this regimen, and they want to stay on it, and they understand the risk, I would be inclined to leave them on the single-tablet regimen with extra monitoring for this patient. But that's just my clinical opinion. You definitely also may want to just have this discussion with the patient that you're going off-label and that there are some risks associated with this. But for me, I just have this huge fear of switching somebody's medication that's working well for them and potentially putting them in a situation where they're not happy with their medications. There's also the switch to cabotegravir plus rilpivirine as well. So, they might not even have to take a pill at all.
Dr. Patel: That's a great point. Yeah. I mean, at the end of the day, the most important thing is to achieve an undetectable viral load. And if this is what they're going to take and they're willing to take, you know, it truly is a risk-benefit conversation.
Another question that came up in the chat box is what are some of the largest barriers to deep prescribing, and how would you recommend overcoming them? One of the biggest barriers that I see is there there's – there's like a cultural attachment to medications. And if you've been on medications for a long period of time, you're feeling well and you've achieved certain goals, I think people are just very reluctant to stop a medication when – when they're doing well. And I don't think people really understand the implications of polypharmacy because they don't happen immediately and they happen downstream. So, I think trying to convince people to stop medications, especially non-ART medications that they may or may not need, there's like a cultural attachment to staying on those – those meds.
Dr. Horace, do you have any experiences with deprescribing barriers?
Dr. Horace: My experience is just a little bit different. I get highly complex patients with multiple disease states, and when I have an MTM, they come with 30-35 medications. And they're asking me, "I need to get rid of something. Like, we have to stop something." And I'm really eager to do that. But some of the challenge is that they need most of it because some of – they have, you know, cardiovascular disease. They've had a heart attack. That's five meds. They have diabetes. That's three meds. And so it's really trying to find those medications that are extra that we can get rid of.
And then just one more challenge is that many of our patients at my clinic, they may have outside providers or specialty providers that are prescribing some of these agents. And so when I do find duplications of therapy or issues with those medications, it's not the provider that I'm working with that's prescribed it. They're outside of my system. So, I'm trying to work with people outside of my system to help this person. So, I usually try to transition my patients to my clinic, where our infectious disease doctors are also primary care. That way, I have a little bit more control over the de-escalation process.
Dr. Nimish Patel: Okay. I think that kind of wraps up the amount of time we have for Q&A. Thank you, everyone, for joining us, and we hope to see you at another CC0 ProCE program.
Dr. Horace: Thank you, everyone. Have a great day.