A new test sensitive enough to detect “hidden” HIV is faster, less labor-intensive, and less expensive than the current “gold standard.”
The findings also show that the amount of virus hiding in people who appear to be nearly cured of the virus is about 70-fold larger than previous estimates.
The virus has a knack for lying dormant in immune cells at levels that are too small to detect by all but but the most expensive and time-consuming tests. This has made it difficult to answer a seemingly simple question: How do doctors determine if someone is cured?
“Globally there are substantial efforts to cure people of HIV by finding ways to eradicate this latent reservoir of virus that stubbornly persists in patients, despite our best therapies,” says senior author Phalguni Gupta, professor and vice chair of the University of Pittsburgh Public Health’s infectious diseases and microbiology department. “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.”
HIV spreads by infecting CD4+ T cells, which are a type of white blood cell that plays a major role in protecting the body from infection. Antiretroviral therapies to treat HIV have advanced to the point that people with the virus can have the virus so well-controlled that they could have as little as one infectious virus per million CD4+ T cells.
However, the majority of HIV DNA integrated into these cells is defective, meaning it wouldn’t cause infection anyway. Once therapy is working, it becomes critical to determine if the DNA being detected by a test could actually create more virus and cause the person to relapse if therapy is stopped. Therefore, the test must be able to show that the virus it detects can replicate—typically by growing the virus from the sample.
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To date, the best test available to do this is called a “quantitative viral outgrowth assay,” or Q-VOA. But, the test has several drawbacks: It may provide only a minimal estimate of the size of the latent HIV reservoir; it requires a large volume of blood; and it’s labor-intensive, time-consuming, and expensive.
The new test, called TZA, works by detecting a gene that is turned on only when replicating HIV is present, thereby flagging the virus for technicians to quantify. The TZA test produces results in one week compared to the two weeks needed using the Q-VOA, and at a third of the cost. It also requires a much smaller volume of blood and is less labor-intensive.
“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 says. “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.”
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Because of its low cell requirement, the TZA also may be useful for quantification of replication-competent HIV-1 in the pediatric population, as well as in the lymph nodes and tissues where the virus persists.
The National Institutes of Health supported the work, which appears the journal Nature Medicine.
Source: University of Pittsburgh
