Recent Russian HIV treatment developments do not justify the means

8 fevereiro 2021

Two treatments to cure HIV infection are being developed by Russian scientists and, with proper funding in five years, "the developments can be put into practice" according to a source to the Interfax agency.

Not quite the Berlin Patient

The Federal Biomedical Agency (FMBA) is investigating a utilising the CCR5 receptor. Such strategies are what led to the cure of Berlin and London patients – and not without great risk.

The Russian development, however, is not planning to use donor stem cells, as was done in the previous two cases, but the patient’s own modified cells. These modified cells without CCR5 receptor will be injected into the patient’s body. By doing this the scientists plan to significantly reduce the risks and simplify the treatment procedure.

"The results are good in mice, this development seems to treat as expected. But research on humans requires a lot of money, there are difficulties with this," the source said.

The DNA method

Another Russian institute is using the strategy of separating the DNA from the virus. According to the source, an enzyme is introduced into the body, it "goes along” the DNA of the cells, detects if a virus is present, blocks it and "cuts" this piece out of the cell. In this case, genes are transferred by the virus. Studies in mice seem to show that this method works.

The ends do not just the means

Life4me+ Chairman of the Board, Dr Alex Schneider PhD, noted that whilst both strategies can ultimately lead to a cure for HIV, but on an individual basis. Such research is important for the development of the fundamental science of gene therapy, but neither of these methods can be applied to a mass cure for HIV. That is why these strategies have long been abandoned in the wider scientific community.

For example, for modified stem cells to work properly, you need to know their number, proportional to the ratio of unmodified cells. Moreover, without a standard procedure, when the original cells with the virus are killed and they will simply be replaced with new ones, this method will not work.

“Cutting the DNA of a virus in human cells in vivo is a method that, unfortunately, no-one has yet mastered. There are too many variables to be predicted in advance. Research with the use of CRISPR-Cas9 technology is currently underway, but even with it, not everything is simple. I, myself, was engaged in gene therapy and I know its difficulties: even a very precise technology can make mistakes. There are a huge number of cells in the body and it is not guaranteed that the enzyme will get into the right cells.

It is also indicated that a viral vector be used to deliver the enzyme. But so far there is no such vector that would successfully select only the required cells. Plus, immunity may also be developed against the viral vectors themselves. And most importantly, even with apparent effectiveness, there is a possibility that the cut off part of the gene will be adapted for in the next generation of HIV” says Schneider.

According to Schneider, one of the promising areas of research is the “kick and kill” strategy aimed at the hidden reservoirs of HIV. It is very important here to find the right agents that can shake the virus out of the reservoirs. And although this method still requires research, it could be used en masse.

Another strategy is immune modulation. This includes broadly neutralizing antibodies (bnAbs) and therapeutic HIV vaccines. Their goal is to create adaptive, long-lived immune responses to HIV that control the virus without the need for regular medication - as in the case of the patient from Buenos Aires. Of course, this strategy also has its own difficulties, but it is far more realistic than other methods mentioned I this article. The city of Lausanne, Switzerland, has already begun trials of such a therapeutic vaccine, Schneider notes.

Returning to the topic of the Russian developments, Alex Schneider once again noted that such research is important for the development of fundamental science, but not suitable for curing 38 million people living with HIV around the world.

Autor: Tom Hayes
Tradutor: Tom Hayes