First in Berlin, Now In London, Next In Dusseldorf!

First in Berlin, Now In London: Second Patient Cured From HIV, While Others Are Being Revealed…

It took scientists over a decade to duplicate the number of patients cured from HIV. The London patient is the second person in the world, receiving stem cell transplantation to cure his leukemia while replacing his white blood cells with HIV-resistant version. Professor Ravindra Gupta is the director of the team who took the challenge on this patients and published the result in nature, just a few days ago. A third patient from Dusseldorf is now seeing his disease go into remission following the same protocol. This is USERN Quick Read #11.

Human Immunodeficiency Virus (HIV), is one of the most feared abbreviations and perhaps the most stigmatized infectious disease in the world. Like other viruses, HIV leaves in and feeds from our own cellular protein and DNA production machinery, destroying its host while replicating and leaving to infect many others. HIV’s strength -and perhaps potential weakness given Gupta’s success- is that it’s main targets are special subtypes of our T lymphocytes, the ''CD4+ T cells''. HIV replicates and infects other CD4+ T cells, while destroying behind the one and only crucial member of our immune system that is meant to stop it. Indeed CD4+ T cells, along with CD4+ macrophages, are the mainstay missiles of our battle against viruses including HIV. HIV paralyses the very part of the immune system that is meant to destroy it.

Now back to Gupta’s work, you might ask: How can we create HIV resistant white blood cells? Answer to this question was found years in advance when it was realized that up to 1% of Eastern European population carried a homozygous mutation is the gene encoding CCR5, a necessary co-receptor for HIV to enter CD4+ cells, that prevents HIV binding and entry to these cells, hence making them inherently immune to HIV. 

Gupta’s work now appears to be piece of cake huh? Let’s say the London patient got lucky that he had chemotherapy resistant Hodgkin lymphoma and needed stem cell transplant and that Gupta and his colleagues at the University of Cambridge did the right job to search for a matched donor with homozygous CCR5-delta 32 mutation (CCR5Δ32/Δ32 donor). CCR5 is not the only HIV co-receptor used by HIV, and the patient remains susceptible to HIV virus reinfection with the so-called CXCR4-tropic species.

Compared to the pre-transplant regimen used for the Berlin case some 12 years ago, Gupta and his colleagues used a less intense chemotherapy and radiotherapy regiment. HIV-1 remission was achieved 18 months post-transplantation in this patient, with undetectable HIV-1 RNA, less than 1 copy per millilitre and undetectable HIV-1 DNA in peripheral CD4 T lymphocytes. Viral outgrowth assays show no reactivable virus in the donor resting CD4 T cells in his peripheral blood. Almost everything looks right to say that his HIV has been "cured" along with his Hodgkin’s lymphoma, and he is fine expect for a mild intestinal graft versus host disease. Whether to say they have been "cured" or achieved "long-term remission", the London patient, who has been off antiretroviral drugs for a while, and Timothy Ray Brown, the "Berlin patient" who is still free of the virus, are the only living examples of formerly HIV-positive patients who are now free of the virus off-drug. 

Just days after this report, a third patient, ''the Dusseldorf patient'' is reportedly cured from HIV through the same method. While stem cell transplant cannot be used freely in any patient with HIV, this small, and fast-growing number of patients are proof that HIV cure is possible via gene editing. Not to forget the Chinses twins born HIV-resistant via the CRISPA/cas9 protocol some 6-months ago.

Source: 

https://www.nature.com/articles/s41586-019-1027-4      

https://www.nature.com/articles/d41586-019-00798-3   

https://www.nature.com/news/2009/090211/full/news.2009.93.html

https://futurism.com/the-byte/third-patient-reportedly-cured-hiv-free    

Report by: Farzaneh Rahmani