Criteria used to help establish and reach treatment goals for patients on antiretroviral therapy for HIV.
Grace McComsey, MD, FIDSA: John, I’m going to ask you one thing. Sometimes I give my colleagues in the clinic a hard time. Some of them think a success of treatment is viral load and CD4 [count]. What is a successful HIV [human immunodeficiency virus] treatment in our eyes?
John Koethe, MD: To a certain extent, yes, in the most basic sense the suppression of plasma virus, which is the easiest thing for us to measure, is evidence of success. But a better gauge of success is going to be two things: one, a suppression of virus that is durable and that persists over time and is refractory to viral breakthrough or resistance. And then secondly, a selection of a regimen that fits with the patient in front of you and all of their unique characteristics, be they comorbidities or other personal factors; age, weight, things like that. The principal goal of antiretroviral therapy has always been the same, which is going to be maintain viral suppression or a level of plasma virus below 50 copies per milliliter, and thus allow CD4 reconstitution and ideally protect us from opportunistic infections within the environment. There’s several routes to getting there, and the two things that we need to separate when we think about how we're going to approach this is, one, matching the regimen to the preexisting patterns of viral resistance, and then also matching the regimen within that same idea to the likelihood that this person is not going to take it sufficiently and thus is going to develop viral resistance.
From that end, we obviously predicate our selection of a treatment regimen on a viral genotype, usually one that frequently does not include the integrase inhibitor class but otherwise looks at protease inhibitors [PIs], nonnucleoside reverse transcriptase inhibitors [NNRTIs], and nucleoside reverse transcriptase inhibitors, and we use these sorts of concatenated databases like International AIDS Society to determine what the best drug is. But simply because somebody is not resistant to a certain regimen doesn’t mean that they won’t become [resistant], so if they don’t take their medications regularly. For that reason, we look at the patient and we ask, OK, if we don’t think because of one barrier or another that they’re going to be adherent to either a twice a day regimen or a once a day regimen, we may select something with a higher barrier to resistance, and that could be, for example, a boosted protease inhibitor such as darunavir, which has a very high barrier to resistance, or it could be a newer generation integrase inhibitor. For somebody who might be extremely adherent, that would probably be less than a question.
And then secondly, we want to tailor the drugs to achieve minimal adverse or unwanted effects to our patients. That’s something where it’s critical that we must consider a variety of characteristics, and this can be everything from their neuropsychiatric profile, including depression, and we got into some issues with sort of central nervous system effects of earlier NNRTIs such as efavirenz, but still something we have to keep in mind. We must look at their other underlying comorbidities, be they cardiovascular disease, be they either overt diabetes or even insulin resistance, hyperlipidemia, and other things we may want to consider when we select our individual regimens. We may want to look at what their weight is right now: Are they already overweight and potentially on the way to becoming obese, or are they already obese? And is that something that we may affect with the particular drug that we choose? And then other host factors that may play into it as well. And then finally there’s also patient preference. Some people insist upon a single-tablet regimen; they can only take this once a day. Other people don’t mind if they’re on two drugs twice a day, which obviously is less common now, but something we consider.
Grace McComsey, MD, FIDSA: We have a lot of options. We’re lucky, we can individualize treatment now, as you said. Look at predisposing condition and give them what fits their lifestyle potentially.
Todd Brown, MD, PhD: Another potential factor might be the potential for drug-drug interactions. With boosted PIs, for example, where there’s a potential for a lot of interactions, and in my practice it’s the concern about interactions with statins and needing to use lower dose statins because the boosted PI will inhibit metabolism of the statin and you can get higher levels. And then for dolutegravir and metformin, Osama and I use quite a bit of metformin and I’m sure you all do too, but that’s an important interaction. Manageable, but it’s something that you need to keep in mind.
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Transcript Edited for Clarity