For most diseases, having a robust, healthy immune response is critical to keeping invading microbes in check.

For HIV, scientists are increasingly realizing that an activated immune system is not necessarily a good thing. In fact, it seems to be a key to viral replication and disease progression.

“Disease associated with chronic infections such as HIV may not be so much a result of the virus attacking the host,” wrote researchers in an article released today in Science Translational Medicine, “but rather may be a result of the host’s immune system attacking the virus.”

Scientists have suspected for some time that uncontrolled inflammation is important for HIV replication early in infection. Recent studies, including this one, are providing even more evidence for this hypothesis.

In the study released today, scientists found that an enzyme called IDO1 may be a key part of creating an imbalance between two types of white blood cells in people with HIV.

The researchers believe the enzyme, IDO1, gets activated during the initial acute stage of HIV infection. The immune system usually uses IDO1 to help control infections.

However, IDO1 also appears to kill a particular type of CD4 white blood cell, called TH17, while increasing the amount of a different CD4 white blood cell, Treg.

The changing ratio between the two cell types is linked to faster disease progression in people with HIV. In this study, researchers confirmed that people with faster HIV progression have higher levels of the IDO1 enzyme than nonprogressors.

In essence, the stronger initial immune response, including IDO1 activation, led to further deterioration of the immune system later on.

The authors of the study are hopeful that their results could help doctors determine who might be at risk for rapid HIV progression, so they could start treatment for HIV infection earlier.

“We found that high levels of IDO1 activity predicted faster rates of progression,” said Dr. Joseph McCune, a lead author on the paper, in email correspondence with the Beacon.

“With further validation in larger groups of patients, our findings may later be translated to a clinical test that could help physicians to determine which patients are at risk for such rapid disease progression and which ones are not.”

Additionally, Phase 1 and Phase 2 clinical trials are already underway for drugs that inhibit the activity of IDO1 in cancer patients, and Dr. McCune’s group is planning to test these drugs in primates to see if they help with HIV infection.

Inhibition of the enzyme might be useful in slowing down disease progression, especially in conjunction with antiretroviral therapy.

“If heightened levels of IDO1 activity in fact drive the…cycle of disease progression, then inhibition of IDO1 activity should stop the cycle and provide benefit to the patient,” said Dr. McCune.

“Such inhibition may be particularly beneficial to those who are placed on effective antiretroviral therapy but who, because of continued inflammation, do not experience full immune recovery.”

If the results in primates are promising, Dr. McCune said, “It may make sense to move on to humans.”

Dr. McCune also suggested that it may be helpful to design a vaccine that can specifically increase the amount of TH17 cells, which are decreased by the IDO enzyme.

The results are still preliminary and need further confirmation, but Dr. McCune is optimistic. “Like all research, this study represents an incremental step; in this case, along the way to better understanding of HIV disease.”

“With better understanding, we will hopefully have better ways to treat and to prevent the disease in the future.”

For more information, please see the study in Science Translational Medicine (abstract).