The London Patient- The Way to the HIV Cure

Sharvari Joshi

March 2020 saw the 2nd ever person to be entirely cured of HIV. Though

overshadowed by the COVID pandemic, this is a landmark event for

what was once a global crisis and has claimed more than 30 million

lives.

The “London Patient” as he is referred, was diagnosed with HIV in 2003.

Following a diagnosis of Hodgkin’s Lymphoma, he underwent an

allogenic stem cell transplant with donor cells that did not express

CCR5- a receptor on the surface of host immune cells, used by the virus

to gain entry.

Testing was by way of ultra sensitive viral load assays of plasma, semen,

CSF to detect HIV1 RNA and quantification of HIV1 DNA in samples

intestinal, lymphoid tissue by droplet digital PCR and quantitative real

time PCR. Intracellular cytokines staining to assess T-cell response and

antibody assays to assess humoral response were also conducted.

Remission was reported at 18 months after analytical treatment

intervention of antiretroviral therapy. HIV1 viral load remained

undetectable for up to 30 months.

But what does this mean?

This was the second successful reported cure- the first being the Berlin

Patient, who underwent a similar haemopoietic stem cell transplant

with donor cells with the CCR5-Δ32 mutation , in 2007- and the London

Patient's proves that it is a cure that can be replicated. It is a step in the

right direction- to find a widespread cure for what once seemed like an

incurable affliction.

What’s the CCR5-Δ32 mutation?

CCR5-Δ32 is an allele of CCR5 which introduces a premature stop codon

in the CCR5 receptor locus and this results in a nonfunctional receptor.

So, HIV-1 is unable to bind to it and gain entry in the CD4 T cells.

Individuals homozygous for CCR5 Δ32 do not express functional CCR5

receptors on their cell surfaces and are resistant to HIV-1 infection.

Those with a single copy exhibit lower viral loads and slower rate of

progression when infected

This mutation shows a lot of promise in being the key to finding a

feasible HIV cure. So far, the treatment the Berlin and London Patients

have undergone are too intensive, when current medication can make

the virus undetectable and untransmittable.

With the aim of using this mutation, a clinical trial was started in 2009

in which the patients' cells were genetically modified with a zinc finger

nuclease to carry the CCR5-Δ32 trait and then reintroduced in hopes of

being a cure. This trial also showed promising results.

With further research, the CCR5-Δ32 trait could be the stepping stone

for a full-fledged and widespread cure.

References:

https://www.thelancet.com/journals/lanhiv/article/PIIS2352-

3018(20)30069-2/fulltext

https://www.thebodypro.com/article/genetic-mutation-behind-hiv-

cure

https://en.m.wikipedia.org/wiki/CCR5

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