Emergency department tests HIV screening strategy

For the past year, on an experimental basis “in the background,” Dr. Wilson’s ED started ordering a GeneXpert real-time RNA PCR test for HIV as soon as a reactive antigen/antibody test result is known. Then the research team measured concordance between the Gene­Xpert qualitative HIV assay (not FDA approved) and the standard-of-care Aptima HIV-1 Quant assay on the Panther; calculated and compared turnaround time on the Gene­Xpert to the standard of care; collected GeneXpert actual run time metrics; reviewed ED length of stay and laboratory TAT data for the standard-of-care test; and calculated differences between Gene­Xpert and the standard of care.

“So we took 20 samples of HIV and the research team found that the Cepheid GeneXpert HIV PCR test was concordant with the standard of care 100 percent of the time and the test decreased TAT by more than 2,000 minutes,” Dr. Wilson says, noting two equivocal samples with known standard-of-care HIV RNA results were included. The researchers found that the GeneXpert HIV PCR turnaround time and overall clinical encounter throughput time of about 465 minutes is reasonable for an ED encounter given that only 1.73 percent of patients in their ED have a reactive Ag/Ab screening result.

Based on concordance and throughput, they recommended that formal clinical trials considering real-time HIV RNA testing in the ED be completed, and depending on trial results, that alternative and/or enhanced algorithms be created for ED HIV screening and testing.

Dr. Wilson and colleagues chose to include HCV screening as well as HIV screening in their experiment because of the similarities between the two as public health threats.

“HCV is our other significant infectious disease epidemic and there are overlapping population characteristics around people who are at risk for HIV and people who are at risk for hepatitis C,” he says. When he started studying the role of the ED in this type of screening, there were not a lot of treatment options for HCV, unlike HIV. “Now you essentially have the direct-acting antivirals that are the equivalent of antiretroviral therapy for HCV and you’ll only have to take it for eight to 12 weeks.”

“That means that clinicians faced with a positive test can do something for the patient and decrease transmission rapidly. If we’re going to get out of these two disease states, the issues around linkage and testing and getting people into treatment are very similar,” he says.

It is still rare, however, to find many other EDs that are doing nontargeted screening, Dr. Wilson says. He estimates that only about 100 hospital emergency departments, or fewer than one percent of EDs in the country, are capable of doing high-volume HIV screening.

“Most of us are part of a group within the Society for Academic Emergency Medicine called the Emergency Medicine Transmissible Infectious Diseases and Epidemics Consortium,” a network that can rapidly and efficiently mobilize emergency departments for early detection and response to transmissible infectious disease threats. “That group is probably the only one even thinking about this or doing any HIV screening.” Only a subset of that group with the necessary testing equipment would be able to do real-time testing, Dr. Wilson says. “Right now, I think our colleagues are waiting for an ER that has been doing this for a while to disseminate how you can do it and not get confusion around results.” Even in an ED like his, “We’re still constantly process-improving all of our steps: When should we retest false-positives? When should we have the RNA test? Should we do the RNA right now for high-risk patients?”

There should probably be a screening algorithm separate from the testing algorithm for an acute encounter, Dr. Wilson says, “and right now we don’t have a differentiation of those two. I would feel more comfortable if we eventually would see a fever or a patient you’re concerned is high-risk symptomatic, and then go right to PCR-based testing. On the other hand, we’re starting to see enough variables where a patient might be excluded from that pathway. Pregnancy, lupus, prior vaccine trial for HIV—those should probably all exclude the patients from even going through an HIV antigen/antibody reactivity test.”

More real-time nucleic acid-based testing should be performed in EDs, he says. “And as we get confidence with the test results, we’ll get to see clinicians taking action based on those test results, which might mean giving antiretroviral therapy, seeing higher linkage rates, or seeing better CD4 and viral load testing downstream. Then eventually we’ll see clear differentiation of the algorithms for screening in the acute environment and screening in the public health environment,” because it may not be necessary or cost-effective to move to PCR-based testing as the only modality available. “If I’m at a health fair and at low risk, a cheek swab may be perfectly appropriate. So we may just need to see carve-outs of those algorithms, and that will probably require some clinical trial work to get to each of those carve-outs.”

Right now, he says, “It’s hard for me to advocate to emergency medicine that we should be doing more testing, because I’m going to put a lot of people in a difficult situation given the current technology with 13 percent equivocals. I think most ERs can accomplish linkage to care, even a small community ER. But there are still more questions we need to answer to get emergency medicine to broadly buy into this or broadly make policy recommendations around not only what the academic ERs are doing but what the community ERs are going to do as well.”

For Dr. Wilson, a key message from this screening research is, “We took that CDC algorithm and put it to an acute ED space and learned that it doesn’t quite fit, and that in reality we’re probably a little behind on technology. We probably need to get the technology to match the acute encounter, and that technology is likely real-time nucleic acid-based technology.”

“We’re not there yet,” he adds. “But we’re getting closer based on the fact that the technology at least is existing and some of the companies out there are working on it too.”

Much progress in increasing the ED’s role in screening has been made to date, he says. When Tampa General Hospital’s ED started conducting HIV screening, “Just by doing the antigen test we essentially doubled the screening that was happening in the entire county. We are now doing 1,100 tests a month and that’s a lot of HIV testing. So we’re going to change the prevalence of the disease just because we’re picking up more of it by doing the test.”

Since one in eight people with HIV don’t know they have HIV (representing half of all new transmission), in places that are not doing testing like this, “the disease prevalence doesn’t change. Those are people you can’t get into treatment and you can’t change your transmission rate either. They are people who are ‘lost to care.’ We’ve seen big success with ERs doing nontargeted high-volume screening to identify people and relink people to care who have been lost to care.”

Many states and territories of the U.S. still have much higher than expected HIV rates, he says. “We know from the historical literature that people who know their status and people who start ART early are more likely to retain care and stay in care. Attempts to do this in the ED have been fraught and mixed with testing scenarios that have lots of steps but are not clear and streamlined. It makes it difficult to do this in the ED setting.”

“Where we would love to get to eventually is a place where we know we’ve got the linkage rates, we know the status, and we’ve started medication and can do it confidently.” That’s an achievable goal, in his view, and one to which the ED is well suited. In fact, Dr. Wilson says, COVID-19 reinforced that “we’re not going to solve the HIV crisis—or any highly transmissible infectious disease—without the emergency departments on the front lines.”

Anne Paxton is a writer and attorney in Seattle.