Although the apparent “cure” of a Mississippi baby born with HIV gave hope that the disease could eventually be erased from the planet (see http://www.examiner.com/article/mississippi-toddler-cured-of-hiv. In order to do so, however, all of the virus must be eliminated from the body. However, because HIV exists in both an “active” version that continuously replicates and eats away at the immune system, as well as an “inactive version” that hides in the body’s memory T cells and remains dormant, eradicating the disease could now be a lot harder to accomplish since all of the virus must be eliminated from the body. This has become most evident in a new report published in the journal Cell by Howard Hughes Medical Institute (HHMI) researchers revealed that a “reservoir of latent or inactive HIV that (silently) lingers in a patient’s body may actually be 60-fold greater than previously thought.”
“We’re working very hard on developing better ways to assess the size of this reservoir,” commented lead author Dr. Robert Siliciano, an HHMI investigator at Johns Hopkins University. “But I think there’s a lot more we really need to understand before we do a lot more clinical trials on (HIV cures). When memory T cells respond to the virus and try to eradicate it from the body, they inadvertently become hosts for HIV. The virus ‘“infects’ some of the responding T cells by physically inserting itself into the cells’ DNA. Then, when the T cells go back to a resting state, the HIV is “turned off” and silently hides in its host cell,” he went on to explain.
“When in the resting state the virus is not actively replicating, so the drugs don’t affect it, and the immune system can’t see it, because no viral proteins are being made,” Siliciano explained. “That’s why you can’t cure the infection, because as soon as the patient stops treatment, some of these memory T cells get activated.
The reason scientists were able to cure the Mississipi child starting from day one was because “there are no memory T cells at the time of birth.”
Up until now, researchers would, literally, make a guess as to how many silent T-cells would exist in the body and remove them from an HIV positive patient. These cells would then be “activated” in test tubes with the idea that if they turn the functioning inactive proviruses back on they could then fight the disease. However, the technique only served to reanimate only about 1 HIV provirus out of every million or so T-cells.
However, thanks to a new technique developed by Siliciano and his colleague Ya-Chi Ho, an HHMI international student research fellow in his lab, the researchers were able to use a polymerase chair reaction to study the genomes of the proviruses that had failed to turn on, which remained in 300 out of ever million T cells.
And while it took approximately three attempts to stimulate the 12% or so, Siliciano and Ho were finally able to get them to produce the virus so it could be fought.
Still, they hope that their study will end up discouraging patients from entering into clinical trials testing a “shock and kill” approach to curing the HIV virus until more research us done “because the size of the provirus reservoir is so large, this technique could lead to major damage in the body.”