Scientists, including one of Indian origin, have developed a new low-cost test that is sensitive enough to detect dormant HIV lurking in people who appear to have been cured. The best test currently available to detect replicating HIV virus is called a quantitative viral outgrowth assay (Q- VOA). 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 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 labour-intensive.
“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,” said senior author Phalguni Gupta, professor at University of Pittsburgh. 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 HIV 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 would not cause infection anyway. Once HIV therapy is working, it becomes critical to determine if the HIV 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. Researchers 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.
“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,” Gupta said. Due to its low cell requirement, the TZA also may be useful for quantification of replication-competent HIV-1 in the paediatric population, as well as in the lymph nodes and tissues where the virus persists, researcher said.
The study was published in the journal Nature Medicine.