A single pathway for HIV testing and therapy

A major thrust of the paper the research team is now working on to report its findings involves how valuable quantitative results are for monitoring of treatment, for which RNA testing is a Grade A indication. “From personal experience, if someone comes to the emergency room with a fever and they were recently started on therapy for HIV and their viral load is, say, 150 versus 100,000, it makes a huge difference in my understanding of everything that’s going on with that person,” Dr. Gromer says. He hopes that QT-RNA will be incorporated earlier in the diagnostic algorithm. “Because it will, I think, facilitate earlier initiation of antiretroviral therapy if clinicians knew that the quantitative RNA data was available or would be soon available because the test is already in the lab.”

Some laboratories, Dr. Gromer notes, may not have in-house access to the approved QT-RNA assay or other assays, and that may affect on-site or send-out testing decisions as well as specimen handling and shipping requirements (more stringent for RNAplasma). “At least in the academic setting where I worked, the differentiation assay wasn’t available; it became a send-out test and was more like a three-day test than a 30-minute test. Our study needed to take into account that results could take different amounts of time to become available from different laboratories.”

Despite the researchers working in large academic institutions, Dr. Gromer believes they were able to derive findings that apply to different health care settings. “Every different locale is going to have to some extent different workflows, and every local lab or academic lab has its own constraints in terms of labor cost, what the technicians are trained to do and not trained to do on the actual machines, and reagents they have. So our model had to attempt to take into account at least some of these factors and do sensitivity analyses to say, What if this part does take longer, what if this other part is more costly?”

“In general, what we assumed is our base case is a laboratory that has the capacity to do all of these tests, and then we varied each one in terms of turnaround time in the reasonable likelihood that some laboratories will have to send these tests out.”

In answer to a question posed at the HIV diagnostics conference, Dr. Gromer said some laboratories might need to explore different plasma collection time, shipping, and storage conditions to operationalize the use of plasma rather than serum. “Sending a plasma specimen and sending a serum specimen are not the same in terms of processes and actions that happen to them and the shipping and handling,” he notes. “So in order to implement a laboratory testing schema that utilizes plasma would require an upfront decision by a laboratory to systematically obtain plasma specimens for HIV testing, as opposed to using serum, which I think is a little simpler.”

Another attendee raised the question of laboratory expertise and false-positive HIV RNA results.

“Our model did not examine this infrequent occurrence,” Dr. Gromer says. “From my perspective, false-positive RNA results are extremely rare. If I saw somebody with a positive RNA value at 70 copies per mL or 200 copies per mL, I would follow DHHS guidelines regarding retesting. But I wouldn’t want to base my decision-making on an entire algorithm on those small outliers that can be adjudicated afterward.”

Dr. Gromer’s research project had been underway for a while at Massachusetts General Hospital during his medical residency before he moved to Atlanta for his fellowship. Based on his experience with the Atlanta patient population, he has found HIV a challenge to manage. “There are not the ideal sort of funded wraparound services that we would wish to have. And new diagnoses of HIV and complex management of HIV are commonplace.” There are major structural barriers to return visits and repeat specimen draws, and the more these are required, the less likely successful linkage to care becomes.

Given the barriers some populations face, it becomes important to streamline the approach to diagnosis and treatment without breaking the bank, he adds. “That’s one of the reasons we were so excited to take this on and figure out how to eliminate some steps for the average person who is coming for HIV testing.”

For the standard of care to change, Dr. Gromer says, the CDC would likely need to reevaluate the feasibility of implementing the RNAplasma algorithm with major referral labs and potentially partner with some local labs to understand the barriers to implementation and find ways that it could be cost-effective for them.

More than one approved QT-RNA test could simplify change. “Right now, laboratories invested in one company’s machine for its RNAs may ask what do we do with this large, expensive piece of machinery that we have all these expensive reagents for if you want to do an algorithm with a different sort of pathway.” It would be helpful, he says, if the FDA approved quantitative HIV RNA reporting on serum specimens. “There may be a difference in comfort level from laboratory to laboratory as to whether on a serum specimen they feel comfortable reporting a ‘ballpark’ quantitative value, which might provide a huge amount of value to some clinicians” by streamlining the testing cascade and getting people into treatment. Whether there is confidence in that as a reliable number is likely to vary, he says.

“There is a brief but critical disconnect between the diagnostic and therapeutic chains for addressing HIV,” Dr. Gromer says. “Changing technology and approvals of the new QT-RNA assay have allowed us to bridge diagnosis and treatment initiation into a single pathway without sacrificing cost.” While the SARS-CoV-2 pandemic affected the pace of his research team’s modeling study because most of the collaborators were infectious disease and laboratory science professionals inundated with COVID-related work, “I think the pandemic increased our fervor and our hope that this topic will be present in a lot of people’s minds, particularly laboratory and pathology-associated folks.” He is hopeful that the modeling study showing the benefits of the single pathway will lead to a change in practice and potentially an improvement in HIV diagnosis and linkage to care.

Anne Paxton is a writer and attorney in Seattle. Dr. Gromer’s coauthors are Bernard Branson, MD; Paul Sax, MD; Anne Neilan, MD, MPH; Maya Hajny Fernandez; Michael Mina, MD, PhD; David Paltiel, MBA, PhD; and Emily Hyle, MD, MSc.