Combination Immunotherapy Provides Potential Benefits in Controlling, Reducing HIV


A combination immunotherapy of interleukin-21 (IL-21) and interferon alpha (IFN-alpha) in combination with antiretroviral therapy (ART) is effective in generating highly functional natural killer (NK) cells that can help control and reduce simian immunodeficiency virus (SIV) in animal models, according to a study published in Nature Communications. The investigators said this finding is critical for developing additional treatment options to control HIV/AIDS.

ART is currently the leading treatment for HIV/AIDS, capable of reducing the virus to undetectable levels. However, ART is not a cure, and it is hampered by issues such as cost, adherence to medication treatment plan, and social stigma, according to the study.

In order to reduce reliance on ART, the researchers worked with 16 SIV-positive, ART-treated rhesus macaques. In most nonhuman primates (NHPs), including rhesus macaques, untreated SIV infection progresses to AIDS-like disease and generates NK cells with impaired functionality.

This is in contrast to natural primate hosts of SIV, which do not progress to AIDS-like disease. Determining why natural hosts do not progress or how to stop the progression is a critical step in halting HIV in humans.

The researchers compared animals that received only ART treatment with animals that received ART, IL-21, and IFN-alpha to evaluate how the combination immunotherapy affected the amount of virus in the animals’ tissue.

“Our results indicate the ART plus combo-treated rhesus monkeys showed enhanced antiviral NK cell responses,” said Justin Harper, PhD, in a press release. “These robust NK cell responses helped clear cells in the lymph nodes, which are known for harboring the virus and enabling its replication and, therefore, the virus' persistence. Targeting areas where the virus seeks refuge and knowing how to limit replication facilitate controlling HIV.”

Historically, HIV treatment has focused on the role of T cells in immunity. This study helps demonstrate how NK cell activity can contribute to controlling the virus, according to its authors.

“This opens the door to designing additional treatment strategies to induce SIV and HIV remission in the absence of ART, and, ultimately, reducing the burden HIV is to individuals, families and the world,” said Mirko Paiardini, PhD, in the release.


New combination immunotherapy plus ART expand innate cells critical to controlling HIV [news release]. EurekAlert; May 17, 2021. Accessed May 18, 2021.

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