Real cost of HIV cure

After Berlin man came London man. Both of these men were previously being treated for HIV, but then also developed cancer, both were treated by allogenic haematopoietic stem cell transplantation using bone marrow from a donor with known HIV resistance, following either irradiation or chemotherapy, and following this treatment both men are no longer receiving antiretroviral treatment (ART), and are said to have been cured of HIV.

This treatment approach appears to work because a molecule located within the cell membrane of white cells known as the CCR5 receptor, normally acts as the entrance card for the HIV virus. However, people with a gene mutation do not carry the card, which lends resistance. The patient's new donor cells therefore confer resistance, and the virus can't get in.

Following the report in Nature, this was obviously big news in 2019 and the work by Professor Ravindra Gupta (UCL Infection & Immunity, UCLH) made all the headlines. The good news for the patient was that even months after medication was stopped, "Plasma HIV-1 RNA has been undetectable at less than one copy per millilitre along with undetectable HIV-1 DNA in peripheral CD4 T lymphocytes. Quantitative viral outgrowth assays from peripheral CD4 T lymphocytes show no reactivatable virus ..."

The work demonstrated the role of the cell receptor in immunity and the seeming specific importance of inheriting the associated gene mutation known as CCR5 delta 32, certainly with regard to resistance to HIV infection. This gene will be the focus for developing new gene therapies and vaccines. Although only discovered twenty years ago, the mutation pre-dates HIV by thousands of years, and seems to have an important role in immunity to a wide range of pathogens. However, although beneficial at one level, the gene may also increase susceptibility to other viruses. Furthermore, the fact is that we do not know the full implications of disabling the CCR5 gene and some animal studies have somewhat worryingly shown altered brain function. In a situation perhaps not dissimilar to sickle cell anaemia and malaria, there would seem to be a long history of evolution affecting the geographical distribution of CCR5 delta 32 according to historical epidemics, such as Bubonic plague or Haemorrhagic fevers.

Prof David Curtis, Honorary Professor, UCL Genetics Institute, says, “.. people who have damaging mutations in both copies of their CCR5 gene may tend to have slightly shorter life spans on average. Such people are highly resistant to HIV infection and even those who only have a mutation in one copy of the gene are partially protected against HIV. However, it seems that not having a working copy of the gene may cause problems", and he goes onto say, "Human beings have evolved to possess a CCR5 gene and this means that it must be providing us with some benefit."

In November 2018, Chinese researcher Dr He Jiankui, announced the births of twin girls from embryos that had been genetically altered to resemble those with the CCR5 delta 32 mutation. Commenting, Dr Eric Topol, the head of Scripps Research Translational Institute, referring to this form of gene manipulation work being performed by He Jiankui, said, “This is far too premature” and goes onto say, “We’re dealing with the operating instructions of a human being. It’s a big deal.” 

China outlaws human cloning but not specifically gene editing.

The controversy caused by these studies means there will be a delay before 'mainstream' researchers proceed with gene editing technology to disable the normal CCR5 gene in embryos and create a generation with HIV immunity. However, the mutation will remain the focus for on-going research due to it's importance in curing these two men.