Selecting a Therapeutic Regimen for HIV Treatment

William Short, MD, MPH, AAHIVS: When I’m looking at patient factors such as their CD4 [cell count] and their viral load as they enter into care, one of the things we’ve known throughout the history of HIV is that those patients who present with lower CD4 counts, so those under 200, or those with higher viral loads, more than 100,000, are what we call the problem areas, because they’re the ones that we know are harder to treat. And if you have patients who are presenting or they’re late to care or late to entry, they’re the ones you’re concerned about. So, I want to make sure they have a really potent regimen. because, again, I’m worried, why did this person come into care so late? And I’m worried, are they going to have problems with adherence? So I want to make sure they have a really potent regimen. But…no matter what regimen you use, even a very good highly efficacious regimen, will not perform as well in someone who has a low CD4 count and higher viral load compared to those with a higher CD4 and a lower viral load.

In terms of comorbid conditions, one of the things we’re seeing in the HIV epidemic is a shift from what we used to see as HIV wasting syndrome, where patients were coming in, they had lost weight, they were very cachectic. And now we’re seeing just the opposite. We see an increase in the number of patients who are labeled as obese. And with the obesity coming all the problems of diabetes, hyperlipidemia, hypercholesterolemia, and all those other factors, maybe heart disease. So we’ve seen a shift, and it’s about how to get patients back to their normal health.

The big question I think for all of us, is this shift in weight gain, is it related to the virus itself? Is it related to a return back to health? Or is it related to the drugs? And this is something that’s really been looked at from the beginning when we’re starting to look at drugs and when patients start to gain weight. So they’re the biggest comorbidities. But other things they see, we definitely know that there’s an increase in cardiovascular disease in HIV with a 2-fold increase in the number of events that you see—high blood pressure—let alone other cases such as hepatitis C coinfection, hepatitis B coinfection. We do see quite a number of comorbidities. And I think the biggest problem is, how do you manage those comorbidities in conjunction with HIV and prevent the least number of drug-drug interactions and stability.

Every patient diagnosed with HIV will have baseline genotype testing done. Typically genotype testing is done for the NRTIs [nucleoside reverse transcriptase inhibitors], the NNRTIs [non-nucleoside reverse transcriptase inhibitors] and the protease inhibitors. At this point we don’t do it for the integrase inhibitors because the rate of integrase resistance is about 0.04%, so we don’t really need to do it yet, so we could feel comfortable.

Where we see the highest number of transmitted drug resistance is in the NNRTI class. And that was an issue when we were using a lot of NNRTIs, but now we’ve cut down on that. So, I can feel confident if I’m drawing a genotype today, I can start a patient on treatment because, again, I’m going to use an integrase inhibitor.

The other class of drugs where you’re able to get away without waiting for your genotype results to come back would be using a boosted protease inhibitor because, again, they’re the 2 drug classes where we have the lowest level of transmitted resistance.

When I’m concerned about adherence to the regimen there’s a whole series of factors that go through my head as to who would be adherent, and I must say that when I’m looking at a patient, anyone sitting in front of me who I don’t know, I feel the risk for a nonadherence to a regimen. So it’s always in the back of my mind. So I think now in 2018, 2019, we do have the ability to pick drugs that have high genetic barrier to resistance. When we’re using things such as NNRTIs, unboosted protease inhibitors or maybe the first-generation integrases, we may have started out with a low genetic barrier and then we blew part of that class, and we know with blowing resistance you get cross resistance. So I think now I feel pretty confident when I have someone in front of me, if I really am concerned about their adherence, I would use a second generation integrase inhibitor that’s a high genetic barrier or…a boosted protease inhibitor.

When you first meet a patient, it’s really about doing a thorough history on to find out who they are, what other type of medical problems they have, what other comorbidities are involved because then I can limit in my head what are the drugs that potentially they could work with? And then talking with the patient, it’s really important. The biggest part of it is, what does the patient want? I can want 3 drugs once a day and the patient may want 1 drug once a day. So it’s important to work with patients, make sure they understand, what are they interested in, and then come together with a regimen that will work for them.