Can HIV be cured? Evelyn Trust-funded research at University of Cambridge probes viral latency

The Evelyn Trust held its second showcase evening at the The Møller Centre at Churchill College, giving an insight into some of the medical research and health and wellbeing projects it helps to fund.

The charity gives out grants of up to £250,000, totalling between £500,000 and about £1.5 million, each year in Cambridgeshire.

The trust was established as a charity in 1920 and was owned and managed the Evelyn Hospital in Cambridge. When the hospital was sold in 2003, the funds were invested. Today, the site is occupied by the Nuffield Hospital.

Here, in the first of a series of articles, we look at an example of the work funded by the Evelyn Trust.

Detecting reservoirs of HIV to help develop a cure

Can HIV be cured?

That was the subject of a talk by Andrew Lever, professor of infectious diseases in the Department of Medicine at the University of Cambridge.

Some 36.9 million people were living were HIV in 2017, according to the World Health Organization – including 25.7 million in Africa. Some 1.8 million were newly infected that year with the virus and there are an estimated one million deaths a year from AIDS caused by HIV.

The virus damages the body’s immune system and weakens its ability to fight everyday infections. It can be effectively controlled with antiretroviral drugs, meaning those in wealthy countries who have reliable access to medication typically have a life expectancy close to average, providing they stick to their lifelong treatment.

But in poorer countries without universal health services, these treatments are not always freely available – and any interruption to treatment reactivates the virus. This can be a death sentence.

Antiretroviral drugs work by suppressing the virus – they do not kill it.

The Evelyn Trust funded research led by Prof Lever with Dr Mark Wills and Dr Hoi Ping Mok at the Department of Medicine to investigate viral latency and reactivation – the mechanism by which viruses such as HIV ‘sleep’ and then ‘reawaken’ when treatment stops.​

Prof Lever explained at the Evelyn Trust showcase how HIV infects CD4+ cells in the human immune system.

“Most CD4+ T cells infected with HIV die due to the effects of the virus. However, a small subset of so-called ‘resting’ memory T cells that harbour the virus persist indefinitely – this is known as latent infection,” he explained.

To find these ‘reservoirs’ of HIV, Prof Lever’s lab has developed a highly sensitive assay for latent virus.

Talking earlier this year, he said: “This is the most reliable assay there is to demonstrate that there really are no hidden reservoirs of HIV that might be temporarily ‘sleeping’ and might reactivate at a later date.

“Our Cambridge lab is unique in the UK in being able to carry out this assay.

He was explaining the progress after the technology was used to assess the second person known to have experienced sustained remission from HIV-1 after ceasing treatment, a decade after the first – known as the Berlin patient.

Both had been treated with stem cell transplants from donors carrying a genetic mutation that prevents expression of the HIV receptor known as CCR5.

The Berlin patient had received two stem cell transplants from a donor with two of the CCR5 genetic mutations to treat leukaemia, and underwent total body irradiation.

The second – known as the London patient – received just one transplant and less intensive chemotherapy after being diagnosed with advanced Hodgkin’s Lymphoma in 2012.

Chemotherapy, which can prove effective against HIV as it kills cells, would not be suitable as a standard treatment against the virus due to its toxicity, but these cases offer hope that HIV could

be cured.

Prof Lever explained that new clinical trials are starting to try to eradicate HIV, enabling therapy could be stopped.

Technical advances in latency assays achieved by the lab mean that such eradication can be validated.

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