ART Impacts How HIV Establishes Itself in the Female Reproductive Tract

The human immunodeficiency virus (HIV) is no longer the death sentence it was when the virus was first discovered in 1983. Although patients are living better, longer lives, finding a cure to the disease remains a top priority.

Researchers at the University of North Carolina (UNC) are actively on the hunt for an HIV cure and, for the first time, they identified how antiretroviral therapy (ART) affects the infection in the female reproductive tract. MD Magazine spoke with Angela Wahl, PhD, an assistant professor of infectious diseases at UNC, to dive deeper into the clinical implications and what this means for a condition that affects nearly 35 million people worldwide.

The clinical trial, HBTN052, recently revealed that when patients received ART, there was a 93% reduction in HIV transmission to their partners. Going off of those results, the UNC team used humanized mice models to understand the infection. Regardless of vaginal or rectal entry, HIV quickly establishes itself in the female reproductive tract. Wahl said that they observed an initial influx in CD4 T-cells in this area, which are the cells that the virus wants to infect. The problem here is that the cells that are supposed to protect against infection, CD8 T-cells, do not make it to the tract fast enough so HIV has time to establish itself.

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As expected, ART caused reduced levels of cell-free HIV in both the blood and the cervical vaginal secretions during antiretroviral therapy.

“What we weren’t anticipating were that when we looked at mice that were treated with antiretroviral therapy and had suppressed levels of cell-free virus both in the peripheral blood and cervical vaginal secretions, that we would still find infected cells that were producing viral RNA, both in the cervical vaginal secretions and in the female reproductive tract,” Wahl explained.

One of the challenges standing between investigators and a cure are latently infected cells. ART has suppressed them from actively reproducing viral RNA. This is a good thing, right? Well, the problem is that since these cells aren’t active, they are shield from the immune system. So when something triggers them and the cells start reproducing RNA again, the infection will be apparent. In order to get rid of the virus, researchers need to find a way to awaken latent cells and destroy them.

Is research anywhere near finding that HIV cure? “I don’t think we’re close yet,” Wahl continued, “but hopefully we’ll definitely see that in the future.”

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The takeaway from this study is that patients can significantly reduce their chances of transmitting HIV by taking their ART as prescribed, Wahl said, which only further confirms the importance of patients being diligent about their treatment.

The findings published in The Journal of Clinical Investigation describe a bright future for uncovering a cure one day, but there’s still a lot of work to be done. In the future, the UNC researchers hope to study how the HIV infected cells in the female reproductive tract contribute to how the virus persists in the body.

>>> Watch the full interview with Angela Wahl, PhD, from UNC