The quest to develop a cure for HIV has long been plagued by a seemingly simple question: How do doctors determine if someone is cured? The virus has a knack for lying dormant in immune cells at levels undetectable to all but the most expensive and time-consuming tests.
Scientists at the University of Pittsburgh's Graduate School of Public Health announced in Nature Medicine that they've created a test sensitive enough to detect "hidden" HIV, and yet is faster, less labor-intensive and less expensive than the current "gold standard" test.
The new Pitt test also revealed that the amount of virus lurking dormant in people who appear to be nearly cured of HIV is about 70-fold larger than previous estimates.
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 wouldn't 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.
To date, the best test available to do this is called a "quantitative viral outgrowth assay," or Q-VOA. This test has many drawbacks: It may provide only a minimal estimate of the size of the latent HIV reservoir; requires a large volume of blood; and is labor-intensive, time-consuming and expensive.
Gupta's team developed a test that they call TZA. It 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.