Whilst a person living with HIV can suppress the virus with antiretrovirals, there is no cure. A cure for HIV would be the total eradication of the virus from the body. However, this is not the only option that scientists are looking into. Here are some of the strategies scientists are looking into for an HIV cure.
Shock and kill technique
HIV hides in reservoir cells in the body and can remain silent as long as a patient takes antiretroviral therapy. As soon as a patient stops taking ARTs, the reservoir virus wakes up and starts replicating all around the body again.
Shock and Kill would ‘wake up’ these reservoirs to activate the silent virus. Whilst counter-intuitive, the idea is to wake up every single virus and kill all the activated cells, destroying the reservoir in one go. If one virus survives then there is always a risk that it will be able to duplicate and the virus will return.
Currently, scientists have identified drugs that will ‘shock’ or ‘wake up’ the silent reservoir cells. The next challenge is to identify a drug or method that can subsequently destroy these infected cells and avoid healthy cells. When destroying cells in the body, there is always a risk that drugs will target healthy cells, so this research moves carefully to avoid unnecessary damage.
Pharmacological reactivation of virus as a cure strategy – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4031321/
Lock and Block Technique
The ‘Lock and Block’ technique takes the opposite approach to ‘Shock and Kill’. This method aims to trap HIV in its reservoir cell so that it can never be reactivated. Whilst the virus is still present in the body, it is trapped away so that it cannot escape its host cell and cannot replicated.
This technique is being looked into as an alternative to ‘Shock and Kill’. Scientists are currently testing drugs’ abilities to effectively trap HIV in a host cell without disrupting the genetic material of uninfected cells. Ideally, a drug would lock HIV away then deplete the reservoir so there was no possibility of the virus returning. Current issues that are being researched are drugs not locking away HIV tightly enough.
…new strategy (‘block and lock’), designed to silence the HIV reservoir, rather than eradicate it. The goal of this strategy would be to increase treatment intervals and maybe even obtain a state of ‘HIV remission’.
Due to the non-inducible property of the ‘deep’ viral reservoir, the ‘permanent silencing’ approach could be considered as a suitable cure strategy. Unlike ‘shock and kill’ strategies, this approach focuses on silencing or locking the HIV-1 proviruses in cells.
Stem Cell Transplants
Only one man has ever been ‘cured’ of HIV. Timothy Ray Brown, otherwise known as the ‘Berlin patient’, was cured of HIV after receiving a stem cell transplant for another condition. Due to a rare genetic mutation in the donated stem cells, Brown’s immune system could fight off the HIV in his body. Over a decade later, he is still HIV-free and actively campaigning for HIV research and speaking about his experience.
A stem cell transplant involves destroying the body’s immune system, then introducing new stem cells that rebuild. This is commonly used to treat leukemia, a cancer of the blood and bone marrow that attacks the body. Brown had a stem cell donation from a specific donor who had a rare gene mutation.
Most people have the gene called CCR5 in their DNA. This produces a receptor on human cells that HIV can ‘latch onto’ and thus infiltrate the cell barrier. However, this donor had the mutation called CCR5 – delta32 which produces a receptor that HIV is unable to interact with. The virus can no longer invade human cells and the human host is resistant to HIV.
When Brown received the stem cells with this CCR5 – delta32 mutation, his body DNA adapted and he became resistant to HIV. However, the details behind why Brown was cured of HIV are complex and difficult to repeat. Even repeating the procedure in other patients, their HIV has come back after a period in remission. There are still elements that scientists don’t understand enough to reproduce the results in other HIV-positive patients.
Additionally, stem cell transplants are dangerous, expensive and require very specific donors otherwise the body can reject the new cells. Stem cell transplantation probably won’t become a mainstream avenue for an HIV cure.
AntiRetroviral Therapy as a Cure
It has been shown that treating the virus within the first 48 hours of exposure can significantly reduce the size of the HIV reservoir hidden in the body. This method is suitable for certain people (e.g. new born babies of HIV-positive mothers), but will not work for everyone. In infants born to HIV-positive mothers, those who started ARTs within 6 to 12 months of birth had reduced mortality rates and a smaller HIV reservoir.
However, many people do not get access to HIV treatment early enough and many people do not realise they have HIV until months after they are first exposed. This is another reason why it is important to go for an HIV test regularly so that you always know your status and can act quickly if you do become infected.
Overall, researchers feel that ARTs alone will not make a cure strategy. Instead, ARTs might make up part of a cure package.
…it is apparent that early ART is instrumental in minimizing the pool of latently infected cells and most likely will be exploited further as a means to a functional cure
Early HIV diagnosis and early antiretroviral therapy reduced early infant mortality by 76% and HIV progression by 75%. .
The complexity of HIV infection—which establishes difficult-to-eliminate viral reservoirs very early—means that prompt ART alone may not be sufficient as an HIV cure strategy.
Whilst technically prevention and not a cure, a vaccination would be a powerful tool in beating HIV. Many HIV vaccines have been trialed and only one has had significant results. It is called the RV144 trial which started in 2003, in Thailand. A cohort received a trial vaccine and were tested for HIV three years later. From the volunteers, the rate of HIV was 31% lower in the cohort who received the vaccine compared to those who received the placebo.
This study gave scientists hope that there could be a possibility for a vaccine. However, the strain of HIV found in Thailand is different to the strain found in sub-Saharan Africa, so the vaccine prototype needs to be adjusted the strains of the virus that are most common in South Africa.
There are projects to create a vaccination however, it is complicated to create a lasting vaccination. Researchers at the Desmond Tutu HIV Foundation, an HIV vaccine trial, HVTN 702. This trial, which began in 2016, is predicted to run for five years. HIV-negative, South African adults receive a series of injections at five different time points that rally the body’s defenses against HIV. If successful, this could be the biggest step towards a vaccine and we are closer than we have ever been.
Some trial work has been done to create infusions that give participants protection, but the protection only lasts for a month or so before another dose is needed.
Many diseases in the past have been close-to-eradicated, if not fully eradicated, thanks to vaccinations: polio, mumps, smallpox, tetanus and measles to name a few.
In the intention-to-treat analysis involving 16,402 subjects, there was a trend toward the prevention of HIV-1 infection among the vaccine recipients, with a vaccine efficacy of 26.4% … In the perprotocol analysis involving 12,542 subjects, the vaccine efficacy was 26.2% … In the modified intention-to-treat analysis involving 16,395 subjects (with the exclusion of 7 subjects who were found to have had HIV-1 infection at baseline), the vaccine efficacy was 31.2%
In all, vaccines have brought seven major human diseases under some degree of control – smallpox, diphtheria, tetanus, yellow fever, whooping cough, polio, and measles.
Still Searching for a Cure
Research is still ongoing to find a way to beat HIV. Until there is a cure, HIV-infected people should access ARTs as soon as possible and stick to their daily dose.
Written by Caroline Reid