Latent Viral Reservoirs Create Hurdle to HIV Cure


HIV reservoirs are resistant to CD8+ T-cells, which eliminate infected cells.

A new study conducted by George Washington University researchers found that latent HIV reservoirs are resistant to CD8+ T-cells, the white blood cells which eliminate infected cells.

Current anti-HIV treatments are very effective at making HIV undetectable, allowing people living with the virus to live longer and healthier lives. These treatments use a class of medications to provide antiretroviral therapy (ART), which also dramatically reduces the possibility of person to person transmission.

Unfortunately, HIV can elude medications by hiding (dormant) in CD4+ T cells. These are the cells which signal another kind of T cell, the CD8+, to kill HIV-infected cells. When someone infected with HIV stops treatment, the virus re-emerges and begins replicating. This will weaken the immune system, raising the likelihood of opportunistic infections or cancers that may sicken or even kill the patient.

Researchers have been searching for methods that eliminate these HIV "reservoirs," where the virus hides. But, researchers at the University of California at Los Angeles, Stanford University, and the National Institutes of Health (NIH) may have found a solution. The approach involves inserting an agent to activate the dormant HIV, which would cause it to start replicating so that either the immune system or the virus would kill the cell containing HIV.

Scientists dubbed this technique "kick and kill." By destroying the reservoir cells, it may be possible to rid some or all of the virus from HIV infected people.

These latent HIV reservoirs have been found to resist attack by CD8+ T-cells. Brad Jones, PhD, the primary author of this study and an assistant professor of microbiology, immunology, and tropical medicine at George Washington School of Medicine and Health Sciences told MD Magazine that they have identified a barrier. He found that, even after using the most potent combinations against these cells, HIV was still present at high levels.

“I do have multiple theories which we are presently exploring [as to why],” Jones said. “The data from our study support the idea that the state of the actual cell that is harboring the latent virus is key, rather than a defect in the CD8+ T-cells. These latently-infected cells have survived for years or decades in these HIV-infected individuals (since they started therapy, or before), whereas many other infected cells have died or been killed by the immune system. The latency of the virus in these cells clearly plays a role in this survival, but perhaps this history has also selected for cells that are inherently ‘tough’. This could explain why these cells are not killed in our CD8+ assays, whereas cells from short-term models of latency are.”

On the chances of overcoming this barrier, Jones was optimistic. “This approach has the potential to eliminate enough of the HIV reservoir that viral rebound is unlikely to occur from the latent reservoir in an individual’s lifetime,” he said.

“I often hear it said that every single HIV-infected cell in an individual would have to be eliminated to achieve a cure (which I would define as a reasonable expectation of a lack of viral rebound over a lifetime) and thus that a cure is extremely unlikely to be achievable,” Jones said. “I agree that it is highly unlikely that we will eliminate every last infected cell from a person, but would ask what is the likelihood that a single remaining latently HIV-infected CD4+ cell would spontaneously reactivate in a person’s lifetime? It might be quite unlikely.”

The study, "Latent HIV Reservoirs Exhibit Inherent Resistance to Elimination by CD8+ T-cells," was published in The Journal of Clinical Investigation.

This article was originally published by MD Magazine.

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