New test could bridge a gap in HIV research

The search for an HIV cure hangs on the ability to detect hidden HIV that can replicate and cause relapse. (NIAID)

Researchers have long sought a cure for HIV, but its ability to hide itself in infected cells makes it difficult to determine if a patient is cured. University of Pittsburgh scientists have developed a new test that spots dormant, replicating HIV and is faster and cheaper than current tests.

HIV spreads by infecting CD4+ T cells, a type of white blood cell. Antiretroviral drugs can dramatically slash the amount of HIV a patient has to very low levels. But it is crucial to determine how much virus is left and if the remaining virus is capable of reproducing and causing relapse if the patient is taken off therapy.

“Globally there are substantial efforts to cure people of HIV by finding was to eradicate this latent reservoir of virus that stubbornly persists in patients, despite our best therapies,” said Phalguni Gupta, a professor and vice chair of the Department of Infectious Diseases and Microbiology at the University of Pittsburgh’s School of Public Health. “But those efforts aren’t going to progress if we don’t have tests that are sensitive and practical enough to tell doctors if someone is truly cured.”

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The current “gold standard” for checking the amount of virus and its ability to replicate is a “quantitative viral outgrowth assay,” or Q-VOA. But this is expensive, time-consuming and requires a large volume of blood. For example, the laboratory of Deborah Presaud, M.D. at Johns Hopkins requires 40 to 150 milliliters of blood for its Q-VOA test. The test costs $1,200 and takes 4 weeks to produce results.

The Pitt team created a test, dubbed TZA, that screens for a gene that is only switched on in the presence of replicating HIV. At one-third the cost of the Q-VOA, the TZA test returns results in one week, needs less blood and is less labor-intensive than the Q-VOA, according to the statement. The research is published in Nature Medicine.

The TZA test also showed a much larger amount of dormant HIV in patients who appeared to be cured.

“Using this test, we demonstrated that asymptomatic patients on antiretroviral therapy carry a much larger HIV reservoir than previous estimates—as much as 70 times what the Q-VOA test was detecting,” Gupta said.

But he isn’t discounting the utility of the Q-VOA test: “Because these tests have different ways to measure HIV that is capable of replicating, it is likely beneficial to have both available as scientists strive toward a cure.”

In the past, scientists have tried to attack latent HIV by causing it to reveal itself and triggering an immune response, but this approach has seen limited success. A team from the University of North Carolina discovered that HIV lies dormant in macrophages as well as T cells, providing a new target for anti-HIV drugs. And University of Melbourne-led researchers used a generic alcoholism drug to “wake up” dormant HIV and are now on the hunt for a second drug that will kill the virus.