StemCell Therapy

1st December is World AIDS Day which raises awareness of HIV and AIDS around the world. There have been huge leaps in the treatment of HIV and AIDS in recent years but its still important to raise awareness and support people to live well with HIV.

To mark World AIDS Day 2019 there are a number of initiatives happening around the world. The Terrence Higgins Trust is campaigning to end HIV transmissions in the UK by 2030. The National AIDS Trust is encouraging people to Rock the Ribbon Together and wear their red ribbon to take the isolation out of HIV, show support for people living with HIV and commemorate those who have died from an AIDS-related illness. The World Health Organization and UNAIDS are recognising the essential role of communities in the AIDS response at international, national and local levels.

What are HIV and AIDS?

Human immunodeficiency virus (HIV) affects the bodys immune system and damages the cells. The virus continues to affect the immune system which leads to immunodeficiency. This makes people with HIV more susceptible to infection and disease as the immune system cannot fight them.

Acquired immunodeficiency syndrome (AIDS) is the collection of illnesses, symptoms or infec-tions that can affect the individual when their immune system has been severely affected by HIV. These can be life-threatening.

MSD has been at the forefront of several break throughs in the HIV field

Symptoms and infection

If people are not receiving effective treatment, HIV can be transmitted via some body fluids, including through condomless sex, blood transfusion, contaminated needles, and vertical transmission (from mother to baby during pregnancy or through breastfeeding.)

People may not be aware that they have acquired HIV because they may only experience flu-like symptoms. This is called a seroconversion illness and common symptoms include sore throat, fever and a rash.

According to the Terrence Higgins Trust (THT), seroconversion is a sign that the immune system is reacting to the presence of the virus in the body. Its also the point at which the body produces antibodies to HIV. Once seroconversion has happened, an HIV test will detect antibodies and give a positive result.

Seroconversion illness happens to most (but not all) people shortly after infection. It can be severe enough to put someone in hospital, or so mild that its mistaken for something like flu although a blocked or runny nose is not usually a symptom.

If a person has recently acquired HIV and has not been diagnosed and started treatment, some of their body fluids (eg blood, seminal fluid, vaginal fluid) can be infectious in the early weeks and months after transmission. However, once a person has been diagnosed and is on effective treat-ment, their viral load becomes undetectable, which means they cannot pass on HIV. It can take up to six months from starting treatment to becoming undetectable, but many patients achieve an unde-tectable viral load much sooner than that.

Developments with treatments

There are more than 25 anti-HIV drugs, divided into six classes. Each class works against HIV in a specific way with most people on a fixed dose combination pill. THT classes these as:

Antiretroviral therapy

Antiretroviral therapy (ART) is medication which stops the virus from reproducing in the body. It can reduce the amount of virus in the blood to undetectable levels meaning it cannot be passed on. It is recommended that people start antiretroviral treatment as soon as they are diagnosed with HIV.

PrEP

PrEP, or pre-exposure prophylaxis, is a drug taken by HIV-negative people to reduce the risk of getting HIV. PrEP is a two NRTIs combination drug, which blocks HIV and considerably reduces the risk of transmission. PrEP is taken either on a daily basis or as event-based therapy (on the days before, of, and after condomless sex). However, dosing recommendations will depend upon the type of sex (anal or vaginal). There is currently a PrEP IMPACT Trial taking place in England until the end of 2019, which is recruiting 26,000 participants who are at high risk of HIV. The trial is to assess the need for PrEP in England, not the effectiveness of PrEP, which has already been established in earlier trials.

RIVER study

The RIVER study was a clinical trial designed to wake up and then kill the HIV virus in people in whom it was controlled by antiretroviral treatment, in the hope that by doing so, researchers would be able to cure HIV by completely eradicating the virus from the body. The RIVER study ran from 2015 to 2018 and was led by investigators from Imperial College London, the University of Oxford, MRC Clinical Trials Unit at UCL, and the University of Cambridge.

On publication of initial findings, RIVER Chief Investigator, Professor Sarah Fidler of Imperial College London, said: In the RIVER study, we found that all the separate parts of the kick and kill approach worked as expected and were safebut the study has shown that this particular set of treatments together didnt add up to a potential cure for HIV, based on what weve seen so far.

Remission

There have been two confirmed cases of HIV remission reported. The first case, the Berlin Patient received a stem cell transplant from a donor to treat leukaemia. The donor had two copies of the CCR5 32 allele, a genetic mutation that prevents expression of an HIV receptor CCR5.

In March 2019, news was released that HIV remission had been achieved in a second person. The case, published in Nature and carried out by scientists at University College London, Imperial Col-lege London, the University of Cambridge and the University of Oxford, said a second person had experienced sustained remission from HIV-1 after ceasing treatment. The male patient was diag-nosed with HIV infection in 2003 and had been on antiretroviral therapy since 2012. Later in 2012, he was diagnosed with advanced Hodgkins Lymphoma. In addition to chemotherapy, he under-went a haematopoietic stem cell transplant from a donor with two copies of the CCR5 J32 allele in 2016.

Despite these two cases, researchers say the treatment is not considered appropriate due to the tox-icity of chemotherapy. However, understanding the mechanisms behind these cases may lead to a potential cure in the future.

HIV treatment has progressed significantly in recent years meaning that people living with HIV and receiving appropriate treatment can expect a normal life expectancy

Becoming undetectable

An important breakthrough in HIV research looks at transmission from an HIV positive person to an HIV negative partner. Two studies, PARTNER 1 published in July 2016, and PARTNER 2 published in 2018 and reported in the Lancet in May 2019, both report zero HIV transmissions from a positive partner on ART to their negative partner through sex without using a condom. In PARTNER 1, this was after nearly 900 couples, both heterosexual and gay, had sex more than 58,500 times without using condoms, and in PARTNER 2 almost 800 gay couples had sex more than 77,000 times without using condoms.

Together, these studies contributed to the evidence that led to Undetectable = Untransmittable and support U=U. This means there is zero risk of transmitting HIV when viral load is undetectable.

The 90-90-90 UNAIDS targets call for 90% of those living with HIV to be diagnosed, 90% to be on treatment and 90% of those treated to have an undetectable viral load.

By November 2018, public health data suggested that the UK was doing well against these targets with 92% diagnosed, 98% on treatment and 97% having an undetectable viral load.THTs Cant Pass It On campaign to end HIV transmission altogether and end stigma about the virus, is raising awareness of the facts around HIV and effective treatment, communicating that someone living with HIV and on effective treatment cant pass it on.

MSDs work in HIV

MSD has been at the forefront of several breakthroughs in the HIV field including being the first to publish the crystal structure of HIV protease. New scientific innovation remains crucial but beyond this, MSD continues to stand alongside the global community of people living with HIV. Living well with HIV starts with a person knowing their status and accessing effective treatment, but the needs of the HIV community go well beyond this.

In the UK, MSD continues to partner with the community to tackle stigma and inequalities and help put people at the centre of their own care. The Whole Person Care Partnership is a group of lead-ing HIV organisations which have worked with MSD to establish the importance of sound public policy in these areas.

Anyone whose HIV is undetectable in the blood cannot pass on the virus sexually. This concept is known as Undetectable Equals Untransmittable or U=U. MSD recently collaborated with its Whole Person Care partners in a U=U social media campaign, reaching more than half a million people. The campaign draws links between U=U and stigma, self- management, care planning and inequalities. Such initiatives are just a start and the short films making up the campaign can be found on the MSD-in-the-UK YouTube channel. The aim for everyone involved in the HIV field is to make living well with HIV a reality, one day, for everyone.

The future

HIV treatment has progressed significantly in recent years meaning that people living with HIV and receiving appropriate treatment can expect a normal life expectancy. Work still needs to be done but organisations from the pharmaceutical industry to THT and the World Health Organiza-tion are working hard to change the landscape.

With thanks to British HIV Association and Terrence Higgins Trust

Go to http://www.bhiva.org and http://www.tht.org.uk

Sources:

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Living well with HIV and AIDS around the world - Pharmafield

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