HIV cure failure in Mississippi baby ‘the beginning of a new chapter’

Medical News Today, UK

29/08/2014

 

Written by Honor Whiteman

Last month, the near possibility of an HIV cure was crippled; the “Mississippi baby” – a child believed to have been functionally cured of HIV – was found to have the virus once again. But although this news is disappointing, researchers from Johns Hopkins Medicine in Baltimore, MD, say we should not be disheartened, as such “failures” bring us closer to finding a cure for HIV.

In March last year, Medical News Today reported that researchers from Johns Hopkins Children’s Center, the University of Mississippi Medical Center and the University of Massachusetts Medical School had functionally cured a 2-year-old infant born with HIV, meaning the child had no detectable signs of viral replication in their blood after combination antiretroviral therapy (ART) had ceased.

The research team said the results were likely to be down to prompt ART administration, which the child received within 30 hours of birth.

By October – 18 months after the child had stopped receiving ART – there were still no signs of viral replication, which the researchers say provided “compelling evidence” that if an HIV-positive child is started on ART within the first hours or days of infection, viral remission is achievable.

But a blow came last month when, during a routine clinical care visit, doctors found detectable levels of HIV in the child’s blood. Furthermore, they found the child had reduced levels of memory immune cells known as CD4+ T cells – a sign that the virus is actively replicating.

Last year, there were also two other reports of adults being in remission from HIV for months after stopping ART and undergoing bone marrow transplantation for cancer. But, as in the Mississippi child case, the virus eventually returned.

But in a commentary published in the journal Science, Dr. Robert Siliciano and Janet Siliciano, PhD, of Johns Hopkins Medicine, say that these cases are “not the end of the story but the beginning of a new chapter.”

The duo notes that the fact the Mississippi child remained in remission for so long is a therapeutic goal in itself, and that finding ways to promote long-term remission and closely monitor it “will be the next frontier in HIV treatment.”

Memory T cells ‘single most important hurdle to eradicating HIV’

The Silicianos say that all three cases confirm that CD4+ T cells are the single most important barrier to break through when it comes to finding a cure for HIV.

These memory T cells are responsible for fighting foreign invaders that they have come across previously. During early HIV infection, the virus DNA occupies the memory cells and lies quietly within them. When these memory cells awaken in response to an invader, however, the HIV DNA is activated and virus replication is triggered.

The team says that ART only fights HIV when it is actively replicating and is unable to reach it when it is dormant in the memory cells. But they say the three recent HIV “rebound” cases indicate that an HIV cure may lie in eradicating infected memory cells.

Dr. Robert Siliciano explains:

“Clearly, neither approach managed to eradicate all latently infected cells, and what these cases underscore is the ability of even a few such cells to rekindle infection after prolonged remission.”

Measuring and monitoring presence of infected memory cells

These three cases, the Silicianos say, also emphasize the need for better ways to measure and monitor the presence of these infected memory cells in the body, as this information could indicate how long an individual is likely to be in remission.

They note that even the most sophisticated tests can miss the presence of infected memory cells. But they say this may be down to the size of the blood sample tested rather than a problem with the sensitivity of the tests.

They explain that reservoirs of infected memory cells only occur in a few out of millions of immune cells, and only around 2% of these cells circulate in the blood at any given time. Therefore, it can be challenging to detect such cells, particularly when the number is reduced. The Silicianos note, however, that even larger blood samples may not be able to detect these cells.

Although the presence of infected memory cells may indicate the length of time a patent is likely to be in remission, the team warns that this remission time may vary in each patient. If a patient has other infections, for example, this may activate the memory T cells and trigger the HIV infection that lies within them.

The Silicianos say it is possible a patient may never experience a relapse but that they are at risk of one even if they only possess one infected memory T cell. This, they say, emphasizes the importance of regular blood monitoring so infected cells can be detected early.

Commenting on the lessons that can be taken from the three “failed” HIV cure cases, Dr. Robert Siliciano says:

“Heartbreaking as these three cases are clinically, they provide a dramatic illustration of the real barrier to an HIV cure and illuminate important therapeutic strategies.”

Medical News Today recently reported on a study by researchers from the University of Washington, which detailed how a dissolvable, drug-loaded tampon could one day protect women from HIV.