In a study recently published by PLoS One, researchers found that a laboratory marker could effectively predict whether combination antiretroviral therapy (cART) will fail in HIV patients.

The standard of care for treating HIV infection is combination therapy, which involves the use of several antiretroviral drugs to help reduce the chance that the virus may become resistant to one of the drugs used for treatment.

Normally, this type of therapy is considered successful when the levels of virus in the patient’s blood plasma reach undetectable levels. Sometimes, however, this initial success is followed by failure of therapy, often for unexplained reasons.

The researchers studied 26 patients who were undergoing cART and had achieved undetectable levels of the virus in the blood, which is also known as viremia. Of these patients, 11 maintained undetectable viral loads, while the remaining 15 underwent subsequent cART failure.

Researchers found that levels of HIV-1 unspliced RNA (usRNA) in peripheral blood mononuclear cellscan indicate the outcome of combination therapy in patients. These blood cells have a round nucleus, such as lymphocytes, and are an important component in the immune system.

For the purpose of the study, researchers measured levels of different HIV-1 DNA and RNA, which play vital roles in the process of viral replication in those blood cells at various times during the period of suppressed viremia.

Levels of usRNA were measured from blood cell samples of HIV-1 infected individuals using laboratory extraction techniques. Levels of usRNA were consistently higher in patients who later experienced cART failure.

Before this finding, HIV-1 viremia, CD4 cell counts, and HIV-1 DNA levels in those blood cells were associated with subsequent treatment failure.

The new discovery answers prior questions about the connection between CD4 cell counts and outcome of therapy. Latent CD4 cells can serve as reservoirs for HIV in patients undergoing cART. These reservoirs stand in the way of complete viral eradication.

Sometimes, a small fraction of these latent CD4 cells can be reactivated. Although only a small amount of CD4 cells are activated in this manner, each cell contains nearly 4000 copies of HIV-1 usRNA. The researchers believe that much of the usRNA sampled in this study was derived from activated CD4 cells.

Thus, high levels of usRNA, which is found in CD4 cells, are strongly associated with therapy failure.

In this way, usRNA fills the missing link between CD4 cell count and outcome of therapy. In fact, the researchers eventually found that usRNA levels of patients under cART was a better indicator of treatment outcome than baseline CD4 cell counts.

With this new discovery, patients undergoing cART can be better prepared to plan the course of future treatments should combination therapy fail.

For more information, please see the PLoS One website.