New test detects latent HIV more accurately, moves closer to cure

Researchers are moving closer to fully curing HIV by designing a more accurate, cost effective, and efficient test for detecting how much of the virus is left in the human body.

The greatest challenge for researchers who have been hard at work trying to come up with a cure for HIV is detecting the virus after retroviral therapy. HIV can "hide" in immune cells at levels that are hard to identify.

Current anti-HIV therapy suppresses the infection to an almost undetectable level, but the virus can persist in a dormant form in CD4 T cells, which are also called T cells or T helper cells. However, most of the HIV DNA in these cells is defective and cannot cause infection.

CD4 T cells are lymphocytes, which are white blood cells with a key role in protecting the body against infection. T cells "alert" the body that there is an infection, activating its immune response. When the body is infected with HIV, it uses these cells to replicate and spread.

The ability of the HIV virus to lie dormant in a "reservoir" of CD4 cells has been the main obstacle to finding a cure; once a patient starts antiretroviral therapy, it becomes very important to tell how much virus is still left, and whether it can replicate.

Most tests available for detecting the virus are not very cost effective and take a lot of time. The most widely available test at the moment is the "quantitative viral outgrowth assay" (Q-VOA). It requires large amounts of blood, a lot of work, and is quite expensive. Additionally, the Q-VOA may also underestimate the amount of virus left.

But now, researchers from the University of Pittsburgh's (Pitt) Graduate School of Public Health in Pennsylvania announce that they have come up with a quicker, easier, less expensive, and more efficient way of checking whether or not HIV is still hiding in CD4 cells.

The new study - published in the journal Nature Medicine - details the new test, which the researchers have dubbed the "TZA test."

How the new test works

The senior author of the study, Phalguni Gupta, Ph.D., professor and vice chair of Pitt Public Health's Department of Infectious Diseases and Microbiology, explains what motivated him and his colleagues to come up with a new test:

"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. 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."

TZA works by detecting a gene that is active only when replication-competent HIV is present.

The TZA test produces results in 7 days, compared with the 14 days needed by the Q-VOA, and it costs only a third of the Q-VOA price. Additionally, it requires a much smaller amount of blood and number of cells.

Importantly, the TZA test revealed that in people who seem to be almost fully cured of HIV, the amount of latent virus is actually 70 percent higher than what previous tests were able to detect.

Because it needs fewer cells, the TZA might also be useful for detecting HIV in children, write the authors, as well as in tissue where HIV continues to hide.

Prof. Gupta comments on the findings:

"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. 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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