The Evolution of Antiretroviral Therapy for HIV - Episode 5
Peter L. Salgo, MD: So what about patients in whom nucleoside reverse transcriptase inhibitors are not an option? What do you do then?
Joseph Eron, MD: Well, I can tell you there are very few people where that’s not an option. It really is about people who you don’t really want to give them nucleosides for one reason or another. And it keeps getting easier. With this newer drug, tenofovir/alafenamide (TAF), we used to get into trouble when people had modest renal dysfunction because we weren’t as sure what to do and the nucleosides got us a little bit. But now, with this tenofovir/alafenamide, you can go down to a creatinine clearance of 30. I think the hardest group are people that have real renal dysfunction; that’s an issue. Or transmitted drug resistance that’s multi-drug resistant, which is really uncommon. I can’t really think of too many other scenarios.
Paul E. Sax, MD: What comes up sometimes is that despite the fact that most of the time the integrase inhibitors are really well tolerated, there are some people who have neuropsychiatric, psychostimulatory reactions.
Joseph Eron, MD: You started them on the integrase inhibitor, but then you have to back off. But you don’t know that in advance.
Paul E. Sax, MD: Correct.
Joseph Eron, MD: You can’t pick those people?
Paul E. Sax, MD: You cannot pick those people, but they’re still drugs. They’re not placebos.
Joseph Eron, MD: Right, sure. I completely agree with you.
Peter L. Salgo, MD: Let me run down a couple of other problematic cases. How do you approach patients with very high viral loads (100,000) or low CD4 counts (less than 200)? Are they special? Are there specific drugs you like?
Eric S. Daar, MD: There are not anymore. There used to be specific drugs we tried to avoid in those people. For the overwhelming majority, it was a nonissue. And all of those drugs that we try to avoid are no longer generally considered first-line therapy. So, unless you have some particular attraction to a certain drug, it rarely matters.
Joseph Eron, MD: But there are some misconceptions out there. You go to meetings, and even some experienced HIV treaters believe that if you have a low CD4, you should get a protease inhibitor. And the evidence for that is pretty much zero.
Paul E. Sax, MD: Yes. I think it has to do with the fact that the first life-saving drugs in the mid-90s were protease inhibitors.
Joseph Eron, MD: Yes, I think you’re right.
Paul E. Sax, MD: So they remember that. The clinical outcomes were first demonstrated in that famous study, where protease inhibitor-based therapy goes up and the deaths from AIDS go down. So, you know that figure went into everyone’s minds: “You’ve got to use a protease inhibitor for patients with AIDS.” But it’s not true.
Peter L. Salgo, MD: How about this case—antiretroviral therapy in HIV-infected women during pregnancy?
Joseph Eron, MD: That’s a tough one, and Paul mentioned that right in the beginning because we just have less information. For some of these new drugs, like dolutegravir and tenofovir/alafenamide, there really are no data for them in pregnancy or the data are very limited. The treatment array shrinks, but we have pretty good advice. Raltegravir, an integrase, is okay to use during pregnancy. So, you can certainly pick a reasonably well tolerated, very effective therapy, but it might not be the top-of-the-shelf choice that Paul was picking off of earlier, and that’s a shame, actually.
Paul E. Sax, MD: It’s interesting. For example, consider tenofovir/alafenamide, which is the safer version of tenofovir/disoproxil fumarate. There’s really no experience with that drug in pregnancy at all. At our institution, where we’re treating pregnant women, we use the old-fashioned version of tenofovir plus raltegravir, whereas we would not choose that regimen for a newly diagnosed patient in any other context.
Eric S. Daar, MD: Of course, there were people using AZT (azidothymidine) in those patients.
Paul E. Sax, MD: I know, it’s sort of ironic.
Eric S. Daar, MD: This is much better than where we were previously.
Joseph Eron, MD: Clearly.
Paul E. Sax, MD: It is also worth saying that most of the pregnant women who are newly diagnosed are extremely healthy. The exception are the ones who acquired HIV as babies. They’re extremely challenging, and usually they have bad resistance.
Joseph Eron, MD: That’s a different story.
Peter L. Salgo, MD: It sounds like a balancing act to me. I mean, if you’ve got a woman who is infected, you would like to treat her for her benefit and for the benefit of the fetus. On the other hand, you don’t know about the drugs.
Joseph Eron, MD: But one of the things that does get done consistently is HIV testing in pregnancy. So, as Paul mentioned, healthier women are more likely to get pregnant. Unhealthy HIV-infected women are probably less likely to get pregnant.
Paul E. Sax, MD: Definitely.
Peter L. Salgo, MD: Let me ask a very quick question. HIV-positive with a positive viral count in a pregnant woman giving birth: if you treat around the time of delivery, and you treat the infant, does the infant become viremic or not?
Joseph Eron, MD: Mostly not. Really, the ones that are are the cases where it’s missed entirely. Unfortunately, women can become HIV-infected during pregnancy, and it previously was recommended to have 1 HIV test during pregnancy. Now, it’s actually recommended that they should be tested twice if they come in early because you’re actually at greater risk of infection during pregnancy because of changes in the cervix and that sort of thing. So, that has occasionally happened, where a woman was tested, was negative, gets infected during pregnancy, and has very high viremia, obviously. This is high risk to the infant, and that’s the scenario where we see transmission.
Eric S. Daar, MD: And there are still rare cases that we all see of women who present in labor that had no prenatal care and are found out to have a rapid HIV test when they come in in labor. And they’ll get antiretrovirals and the baby will get antiretrovirals. We’ll be able to reduce the risk, but it’s not going to be zero.
Peter L. Salgo, MD: Do you test every woman in labor?
Eric S. Daar, MD: If she hadn’t been previously tested during her pregnancy, absolutely.
Transcript edited for clarity.