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HIV Screening and Diagnosis

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Segment Description: Joseph Eron, MD; Paul Sax, MD; W. David Hardy, MD; Eric S. Daar, MD; and Ian Frank, MD provide recommendations for proper screening and diagnostic protocol and considerations of the stages of HIV infection in presenting patients.

Joseph Eron, MD: So let’s move on and talk a little bit about the kinds of stages of infection, Paul. And you can actually, I think, talk about diagnosis here and also maybe remind people that new diagnosis doesn’t necessarily mean a recent infection.

Paul Sax, MD: Sure. Correct. But since we’re talking about stages, why not start at the beginning and realize that people who get infected with HIV can have a clinical syndrome that we call acute HIV infection, which is a lot like infectious mononucleosis. And it’s about estimates: It’s hard to know, but about half the people who require HIV are symptomatic. And then the severity of that illness is really incredibly variable. Everything from a very mild mono-like illness to, you know, I’ve seen someone with very fulminant meningoencephalitis who got admitted to our ICU [intensive care unit] with very severe encephalitis from acute HIV. Interestingly, it was an individual over the age of 50 who was from sub-Saharan Africa, and it was really interesting.
But anyway, the diagnosis during those symptomatic periods early on is actually the HIV viral load test. In most contexts, though, that’s not the test we’re going to be sending when we want to screen for HIV. We’re going to be sending this fourth-generation antigen antibody combination assay, and that has really improved our ability to diagnose HIV after recent acquisition. It’s not quite as sensitive as the viral load test, but it’s almost as good. So that’s our screening test.

W. David Hardy, MD: And its crisis is more expandable. And its turnaround time is also easier to do because it’s ELISA [enzyme-linked immunosorbent assay] as opposed to a PCR [polymerase chain reaction] test so that it can be done more quickly as well.

Paul Sax, MD: I mean, if you’re going to screen someone for HIV who doesn’t have acute HIV infection, someone who you know maybe had risk behaviors a couple of years before, who has never been tested before, is asymptomatic. It’s that fourth-generation antigen antibody test that they’re going to be sending.

Eric S. Daar, MD: But it is important. Paul, as you said, it’s a great test for routine screening. If you encounter someone in whom you have a high index of suspicion, and the fourth generation is negative, they really do need to have an RNA test done.

Paul Sax, MD: It’s amazing that the quantitative HIV RNA test, the viral load test that we use for all our patients—nobody has ever gone to the trouble to get it FDA approved for diagnosis.

Joseph Eron, MD: Interesting.

Paul Sax, MD: Which is annoying, but it’s just not—you can’t use it for diagnosis. One thing that I just also mentioned just clinically because it’s important, is if that antigen antibody test comes back positive, it doesn’t have enough specificity for you to sort of say that’s conclusively the diagnosis, so it has to be confirmed with the second test, which is now called differentiation assay. And in our hospital where we have a large obstetric service and a lot of women who are pretty low risk are getting screened, it’s actually just as common for their screening test once positive to be not confirmed as it is for it to be confirmed. So there is a false-positive rate in that, in that screening assay.

Joseph Eron, MD: So that’s like the kind of acute infection. In Los Angeles, what, how are people presenting now?

Eric S. Daar, MD: Yeah. So I mean, obviously we occasionally see people with acute infection, but the majority of people are coming in for routine screening, or increasingly because of guidelines, like CDC guidelines, people are—even without obvious risk factors—just getting a test. So a lot of people admit to the hospital, people who are going to certainly STD [sexually transmitted disease] clinics and urgent cares are getting screened and getting diagnosed. And I think anecdotally—and I think there are data in other centers—that we are catching people earlier because our threshold screen is now, you know, if you’re a warm body, and we think of it, we should do it.

Joseph Eron, MD: Yeah, sure.

W. David Hardy, MD: And I think the other thing that Paul just mentioned, taking away the obstacles of getting tested make a huge difference. Taking out the consent form, taking out the counseling before and after has really helped. And then also the other thing we’ve noticed in Washington, DC is that if you take the test out of the testing center into the community, people will come and get tested. For many years, they tested people at the DMV [Department of Motor Vehicles] in DC because the incidence was so high. And after you got your driver’s license, you got a chance, you know, to go get tested as well. They stopped doing it because the pickup rate was so small, but it really normalized HIV testing, which is so important.

Joseph Eron, MD: And what about advanced disease? Do you guys see that, people presenting with advanced disease still?

Ian Frank, MD: We see fewer cases in Philadelphia, people coming in with AIDS defining clinical events. And in the outpatient setting we see fewer people with CD4 counts—fewer than 200 at presentation than we have. But occasionally those people still surface.

Eric S. Daar, MD: We still see a lot of people who slipped through the cracks.

Paul Sax, MD: It really is very dependent on the region in which you practice, and whether you do inpatient medicine, because really, the only context I see it now is someone who gets admitted to the hospital with an opportunistic infection, or gets admitted with a mysterious wasting illness that turns out to be not so mysterious after all.

W. David Hardy, MD: In DC it’s really interesting because there’s a real dichotomy between who’s giving chronic infection and who’s not. So in my experience African-Americans are the ones who are coming in very late in large part because of the fact that even though they may know they’re positive, they’re not accessing treatment because of the stigma of taking the treatment, and what that means in their community. So I saw several cases working in DC of individuals who came in with T cells less than 50 and minor opportunistic infections.

Joseph Eron, MD: In North Carolina we still see—you know, we probably have 2 or 3 cryptococcal meningitis. Sometimes there are people who are actually seen in an outside hospital. They’re perceived at being lower risk; they might be a little bit older, like an older woman, for example. They’re perceived to be at lower risk, so the diagnosis isn’t necessarily considered. And the other thing you see is a lot of them have had an opportunity to be tested but they’re not tested.

Paul Sax, MD: Yes. There’s actually quite a bit of literature on this. And every infectious disease specialist has many, many anecdotes of people who bounced from clinician to clinician to clinician getting unexplained symptoms and laboratory abnormalities worked up. You know, the classic example is the bone marrow biopsy that’s done before the HIV test because of leukopenia. I mean that’s just completely crazy these days.

W. David Hardy, MD: 1980s.

Ian Frank, MD: Sometimes it’s not so subtle either. Sometimes it’s, you know, it’s an oral candida that may be seen in a dental office or herpes zoster or where there’s been no HIV test or new cirrhosis. An HIV provider would say, “Hmm, I think this person needs to be HIV tested,” but it doesn’t always happen in a general practice, or another subspecialist’s care.

Paul Sax, MD: One last group of people who don’t get diagnosed. There are some patients who do still refuse testing. And the anecdotal—again, there was a patient I saw from rural Vermont who had been seen by multiple clinicians and several had recommended that he get HIV testing; he kept refusing. And then he insisted on getting a, quote, second opinion at the Boston Medical Center in Boston, Massachusetts, poor guy, and the first thing I said to him was, get an HIV test.

Eric S. Daar, MD: Did he do it?

Paul Sax, MD: But he ultimately did it, but I mean there are some of those people who are so stigmatized by the diagnosis, and also are so afraid, that they just refused to get tested.

Eric S. Daar, MD: I’ll tell you, using the opportunity when you encounter somebody to explain to them how good treatment really is and how everybody has access to the best of treatment. Those are often what drive people away. They can’t access, the treatment isn’t good, the treatment’s toxic, and even if it is good, they can’t get it.

Paul Sax, MD: It’s too expensive.

Eric S. Daar, MD: And that’s just not the case.
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Big advances in treatment can't make up for an inability to stop new infections, which number 5,000 per day worldwide.