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Professor of HIV
Queen Mary, University of London
Lead for HIV Research
Barts Health NHS Trust
The Royal London Hospital
London, United Kingdom
Chloe Orkin, MBChB, FRCP, MD, has disclosed that she has received consulting fees, fees for non-CME/CE services, and funds for research support from Gilead Sciences, GlaxoSmithKline, Janssen, MSD, and ViiV Healthcare.
Although the primary goal of ART is sustained viral suppression, a given patient may require a switch from their current virologically suppressive regimen to a new antiretroviral therapy (ART) regimen for a multitude of reasons. Examples of situations that require consideration for a regimen switch include adverse events, adherence challenges because of the inconvenience of the current regimen, or to prevent a potential toxicity or anticipated drug‒drug interaction with a new non-HIV medication. In more general terms, an ART switch is made in response to an undesirable clinical situation (eg, adverse event), to prevent an unfavorable clinical outcome (eg, worsening comorbidity that raises concern for the safety of a given drug), or because the patient has expressed that there is something about the regimen that is not working for them, and you sense that another option may be better suited to their needs (eg, food requirement for dosing that they find challenging, frequency of dosing).
The decision to switch ART should not be taken lightly, but it also is important to recognize that a regimen change may be necessary to meet the broader goals of HIV therapy, including improving quality of life. The European AIDS Clinical Society (EACS) guidelines note that, “Just because the viremia is suppressed it should not be assumed that the PLWH [person living with HIV] is well adapted and tolerating the current regimen.” In this commentary, I would like to emphasize the importance of 3 features of switch regimen selection: assessing treatment history, considering a regimen’s genetic barrier to resistance, and listening to your patient.
A prominent element that distinguishes the process of selecting an initial ART regimen from the selection of a switch regimen in a patient with viral suppression on their current ART is treatment history, including both available and unavailable information. Often patients may be presenting from another clinic or a different physician within your clinic. The result is that important details may be missing, such as genotypic resistance data. In these cases, the treatment history is essential for anticipating drug resistance and identifying an appropriate switch regimen that would be effective in the face of potential resistance.
Genetic Barrier to Resistance
The EACS guidelines underscore that the primary concern with any ART switch is not to jeopardize virologic suppression. When considering the risk of loss of viral suppression with a switch, differences in the genetic barrier to resistance of different antiretroviral drug classes and between different drugs within a particular class warrant careful consideration. For example, if you are considering switching from bictegravir to raltegravir, you would be reducing the genetic barrier to resistance of the regimen. Another example of a reduction in the genetic barrier to resistance would be a switch from boosted darunavir to rilpivirine. Such switches increase the risk of virologic failure and should be relatively easy to avoid in the current era of HIV therapy, in which we have an abundance of riches in the form of many highly effective and safe regimen options, including multiple single-tablet options, allowing us to formulate individualized switch regimens that harbor a very low risk for loss of viral suppression.
Listening to Your Patient
Another critical action item for making appropriate ART regimen switches is truly listening to the patient. The most common reason for requesting a switch in treatment is toxicity/tolerability concerns, and toxicity/tolerability also is the most common reason people discontinue therapy. Therefore, it is vital that we hear and address our patients’ concerns. If someone expresses that they are experiencing an adverse event with their HIV medication, one of our roles is to consider if/how an ART switch may be helpful. The worst approach would be to ignore their concerns or to wait for a more convenient time to address them (eg, after the pandemic is “over”). This includes situations in which a patient may be describing adverse drug events that you suspect are not likely to be related to the drug(s) in question. That approach can lead to the patient feeling unheard, with the potential for disengagement from care. If they feel strongly that the medications are causing an adverse event and you decline to change their regimen, they may simply stop taking it. Everyone is different, and the fact that a particular adverse event has not been identified as a significant signal in a clinical trial does not necessarily mean that a given patient is not experiencing it because of their regimen.
A perfect example of this is the weight gain that has been associated with switching to some newer antiretroviral drugs, such as next-generation integrase strand transfer inhibitors and tenofovir alafenamide. Patients had been expressing concerns about weight gain after switching to regimens that included these drugs for some time. Initially, we told them: “Oh, well, it’s just the return-to-health effect. Try to improve your diet and get more exercise.” It was only after the clinical studies were done that we eventually realized there really was an association. The association is complicated and not yet understood, but it does exist, and it will require more research to understand the nuances and potential confounding of switching away from drugs that may suppress weight gain. However, in looking back, it should not have taken us this long to realize that the patients were giving us important insights. We probably were not listening as well as we should have been.
In the listening process, it also is important to ask nonjudgmental, open-ended questions to identify challenges that are generally more difficult to talk about, such as mental health. This issue is particularly relevant during the pandemic, when many of our patients have been experiencing significant personal and economic upheaval. We should not be afraid to ask these important questions in a sincere way: “How are you doing? Where have you been living and working? Are you feeling isolated?” Only then can we better understand where they are, how they are interacting with the world, and what effect it is having on their mental and even financial health.
We are optimizing treatment so that people can have good, healthy lives—and that includes situations such as adolescents who are transitioning to adult care and beginning to manage their own lives, people who are wishing to have their genders realigned, and people who are wishing to have a child. Our role is to select regimens that accommodate each of these scenarios as they present, not to try to bend the patient’s situation to match the regimen. In the process of considering other options, we should reflect on the whole person and their different potential risks: their cardiovascular risk, their renal risk, their bone risk, their age, their nonadherence risk, and their life choices.
A New Offering for Switch Therapy
One of the exciting features of the 2021 updates to the EACS guidelines is that, for the first time in the history of HIV therapy, we now have the option of switching to a long-acting regimen—cabotegravir plus rilpivirine administered by IM injection every 1-2 months—for patients with viral suppression on their current regimen. Moreover, the results of a newly published study that I am proud to have coauthored led the European Commission to grant an update to the dosing information that permits individuals to switch to the injectable regimen with or without the 1-month oral lead-in period that was originally required. This update makes implementation of this switch option much easier. There certainly are still logistical considerations regarding how to accommodate delivery of this new option, including the shift from 2 clinic visits per year that is generally required for oral ART monitoring to 6-12 visits per year for monthly or every-2-month injections. It is now up to us as healthcare professionals to try to work out the additional/modified resourcing that will be required for delivering whichever type of therapy our patients prefer.
What are the most prominent issues that you consider when making the decision to switch ART in a patient with viral suppression? Answer the polling question and join the discussion by posting a comment. For more discussion of HIV treatment, download the slides and watch the webcast from our recent EACS 2021 satellite symposium, “Individualized Choices in Antiretroviral Therapy: Present and Future.”