The Evolution of Antiretroviral Therapy for HIV - Episode 9
Peter L. Salgo, MD: Let’s talk about monitoring patients with HIV. Laboratory monitoring: how often do you do CD4? How often do you do HIV-RNA monitoring? Do you do it periodically? Is there a schedule? What are you doing?
Eric S. Daar, MD: It’s something that I think we’ve all laughed at ourselves, in clinics, for years and years, because we’ve routinely ordered these tests every time people came in and we often saw them just as often. But then we would never do anything with the results.
Paul E. Sax, MD: Especially the CD4.
Eric S. Daar, MD: Especially the CD4. So people sort of revisited this. I think there’s a consensus that you want to know what the CD4 is at baseline to know whether they need to be on any prophylaxis, and usually, you get a baseline viral load. Even that, arguably (unless it’s undetectable), is usually useless, because your goal of therapy is undetectable. And I don’t care whether you started at 1000 or 500,000—the goal is the same. And then we monitor viral loads pretty close at the beginning. And some of this is probably because of the idea that if they aren’t responding well or they’re experiencing failure, we want to know it earlier than later. My guess is it’s more a marker for adherence for us, so we’re using the viral load. We’re not going to do anything based on the CD4 for months and months, so the utility of doing a lot of CD4s early on [is] useless. We do the viral load, and once a person is undetectable, then the only reason we’re doing the viral load is to see if they experience viral rebound. There’s a general consensus and there’s data that suggest that once somebody is undetectable for a long time, they’re not likely to rebound unless something happens.
Peter L. Salgo, MD: So, when do you check?
Eric S. Daar, MD: We’re doing it less and less. Usually every 4 to 6 weeks—viral loads at the beginning until their viral load is undetectable. With integrase inhibitors, we check often in the first 12 weeks, and then, probably, most people will do it every 3 months or so for the first year. Then, once things stabilize after a year, every 6 months is probably more than adequate. We probably have some people that are undetectable for 10 years, and we check once a year, maybe, following that.
Joseph Eron, MD: Yes. I’m certainly starting to go to, now that I don’t worry as much about nephrotoxicity of TDF (tenofovir disoproxil fumarate), once a year in a lot of my patients. The interesting thing is we’ve trained so many of our patients to want to know their CD4, and it’s actually a little harder to completely get rid of the CD4. But I think most of us would agree that once your CD4 is above 350 or 400, you could probably just get rid of it, right? I mean, just never do it.
Paul E. Sax, MD: It was a habit. It was hard to break.
Eric S. Daar, MD: And you never react to it. All you do is talk patients off the cliff.
Paul E. Sax, MD: There’s a lot of variability at the higher numbers, just based on that.
Peter L. Salgo, MD: Let me give you some other tests. I have a feeling I know where we’re going with these. Hepatitis A, B, and C; serum chemistries; blood counts; creatinine clearance; urine glucose; proteins; lipids; SMA 20s. What do you do with all that?
Eric S. Daar, MD: I think for viral hepatitis, everybody gets checked at baseline to see if they’re immune to hepatitis A and hepatitis B. If they’re not immune and they don’t have chronic hepatitis B infection, they get vaccinated. So it’s important to have that at baseline. And then, if they have chronic hepatitis B, we treat them as we’ve talked about earlier.
For hepatitis C, everybody gets tested at baseline. And if they’re negative, I think one of the things that is probably the most common thing in the guidelines, that’s missed in a lot of clinics, is that high-risk individuals (which now extends beyond people who use needles, but also men who have sex with men) should be checked probably annually because we recognize an increased risk of transmission within these populations.
Ian Frank, MD: The test that we’re doing most frequently now is screening for sexually transmitted infections. So, RPR (rapid plasma reagin), GC (neisseria gonorrhoeae)/Chlamydia, and not just urine, but rectum and pharynx—there are some people that would argue that those should be done every 3 months.
Eric S. Daar, MD: For certain people.
Ian Frank, MD: They recommend that that be monitored more closely than the viral load.
Peter L. Salgo, MD: Okay. Quickly, serum chemistries? Glucose? Creatinine clearance?
Paul E. Sax, MD: We do monitor those. Those are the safety monitoring labs. They’re now not quite as critical, as Joe mentioned, because the tenofovir formulation is less nephrotoxic. Definitely you want to check lipids, because you know with the aging population, you’d want to treat those if they’re elevated.
Joseph Eron, MD: And the populations that we care for, at least in North Carolina, are [at] super high-risk of diabetes. They’re 60% black in our population. One thing that happens when people get on therapy is they gain weight. Obesity is a problem in our clinic.
Paul E. Sax, MD: In addition, some of the more toxic antivirals we used in the bad old days caused lipoatrophy. And lipoatrophy is strongly associated with diabetes, glucose intolerance, and insulin resistance.
Peter L. Salgo, MD: What about genotypic resistance, reverse transcriptase, and things like that?
Eric S. Daar, MD: So, the current recommendations are that we’re supposed to do it at baseline to look for transmitted resistance. And I think that’s reasonable. The current recommendations are, since most people have to order a separate test for integrase resistance, is to not do that as a matter of routine unless you’re worried that the person may have been exposed to somebody. And then, we do it when people experience virologic failure.
Paul E. Sax, MD: We presented at CROI (the annual Conference on Retroviruses and Opportunistic Infections), a modeling analysis on this question and whether to do baseline integrase testing. And essentially, the answer is no, because the only reason to do it is to then ignore the result. If you’re using a dolutegravir-based regimen, you’re still going to virologically suppress most patients if they have integrase at baseline. And if you don’t suppress them, you’re going to switch them within 8 to 12 weeks to something else—which is, of course, what you do anyway.
Eric S. Daar, MD: And also, you’re testing for something that’s been reported 5 times.
Paul E. Sax, MD: There’s really almost no indication.
Eric S. Daar, MD: So, even when we start seeing transmitted resistance, that may be the case. Right now, we don’t even see it.
Paul E. Sax, MD: It occurs at a rate of 1%, at most, in some series. And a lot of them are polymorphisms that don’t affect the outcome.
Joseph Eron, MD: Actually, baseline resistance testing should probably just go away altogether.
Paul E. Sax, MD: We’re working on that one. We’re focusing, first, on the integrase questions. You’re right.
Joseph Eron, MD: That may have unintended consequences because there’s a lot of work being done looking at transmission clusters and things like that that help identify HIV spread and use that, kind of, “free” test.
Paul E. Sax, MD: That’s right. The rational use of baseline resistance testing would be to not get it.
Transcript edited for clarity.