Curing HIV

Not too long ago HIV was hush-hush and considered a death sentence for those who had contracted it. Luckily that is no longer the case and there are anti-retro-viral drugs for those with the virus. However, it is not a cure and those with HIV still live with this chronic condition, taking daily medications. Could new research bring us closer to a cure for HIV?

invading HIVRoughly 36.7 million people were living with HIV/AIDS at the end of 2016, 2.1 million of these are children under the age of 15. Human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) come hand in hand. AIDS is the most advanced stage of the HIV infection. HIV attacks infection-fighting white blood cells of the immune system, gradually destroying the immune system and was first recognised in the 1980’s. By 1995 there was an anti-retro-viral (ARV) treatment. There are now numerous classes of ARV treatment, each targeting the virus at various stages of its life. ARVs manage HIV but do not cure it, enabling those who have contracted the virus to now live relatively long, healthy lives by taking combinations of these drugs. ARV’s work to prevent two main virus pathways:

  1. Cell fusion: Preventing the virus from entering human cells.
  2. Reverse transcription: Preventing the virus from copying its RNA into our DNA, blocking the virus from integrating with human cells or making copies of itself.

ARVs are not easy to take. They are taken in combination, meaning numerous pills which must be taken every day. The pills have low absorption meaning that they must be very large to ensure more of the drug is absorbed into the bloodstream. Due to this, patients sometimes take ‘drug holidays’ as they have fatigue from the constant regime, allowing the virus to rebound.  arvs

Wouldn’t it be great for patients to not have to take these everyday and instead have a cure for this chronic disease? ARVs suppress HIV, they do not destroy it. Researchers are now investigating the use of gene editing tools like CRISPR (follow the link for a more detailed previous post about CRISPR) to cure HIV; destroying the virus. In theory, the CRISPR procedure is very simple and already proven to work in mice. The technique cuts out HIV DNA from the cells it has infiltrated, replacing it with the correct sequence, eliminating HIV from the infected mouse. The method should easily transfer to humans. However, HIV plays a game of hide and seek, laying undeveloped in unlikely immune cells. CRISPR gene editing could be used to remove HIV DNA from the cells we know about but if left in other immune cells we are currently unaware of, we’d be back at square one: the patient would still have HIV.Gene editing

There is also the risk of turning on a cancer causing gene or turning off a tumour suppressing gene if all the immune cells were edited in this way. What if we could edit our immune cells so HIV could not enter them?

One person is known to have been cured of HIV. Timothy Ray Brown (aka the Berlin patient) was diagnosed with HIV in 1995. He had a bone marrow transplant in 2006 when his immune cells were killed off from chemotherapy used to treat his leukaemia. The bone marrow donor had a rare type of stem cell with a mutation which removed a receptor on the immune cells, preventing HIV from entering them. Timothy was cured of HIV. Rafick-Pierre Sekaly, who researches at Case Western Reserve University in Cleveland, hopes to replicate this with DNA editing tools, inserting the DNA sequence into a patient’s sequence, removing the receptor from immune cells.

hiv mechanism

The procedure itself is minimally invasive. White blood cells are collected from a patient over 3-4 hours, the cells are edited in the lab, grown for 12 days and then the HIV resistant cells are given back to the patient. These resistant cells can then replicate in the body and actively fight the virus. Researchers found that the body was able to replicate these immune cells so that 70% had been replaced by HIV resistant ones over the course of 2-3 years. The HIV infected cells eventually die and they cannot infect the resistant ones. Over the last 5 years, 77 patients have received this treatment which is administered via a couple of injections over the course of a few years.

Thus far there have been no adverse side-effects reported and none like those experienced by those who take ARVs. There are more trials underway for this treatment and Sekaly is confident that this could lead to a cure for HIV. However, price of the treatment is currently hitting $25,000 per patient, much more than it costs to take ARVs. It is likely this cost would come down once on the general market but it is still not a treatment that will be accessible to those suffering in sub-Saharan Africa. This cellular therapy is a big step for the treatment of those living with HIV however, much more is needed to help those in underdeveloped countries.

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