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Data to help fight drug-resistant HIV

A cell infected with human immunodeficiency virus (HIV) examined with a scanning electron microscope (SEM). © INSERM
A cell infected with human immunodeficiency virus (HIV) examined with a scanning electron microscope (SEM).© INSERM

The HIV virus stops at no borders. Now, the international fight-back intensifies.

The EU-funded CHAIN initiative has launched an international databank identifying multiple strains of the human immunodeficiency virus HIV to help scientists develop new drugs which can counter the spread of the killer virus.

World AIDS Day celebrates its 25th anniversary on 1 December 2013. Since the first reported death from AIDS, the disease caused by HIV, in 1981, an estimated 35 million people have died as a result of contracting the HIV infection.

HIV/AIDS has spread so quickly that, just 20 years later, the British Medical Journal predicted that the virus would surpass the Black Death as the worst pandemic of all time.

But a huge drive in humanitarian and scientific activity over the past decade – the European Commission alone is currently spending around EUR 155 million on HIV research through its 2007 to 2013 funding programme FP7 – is starting to turn the tide against it.

CHAIN reaction

The five-year CHAIN project is looking directly into tracking and limiting the spread of drug-resistant HIV strains. ‘We still have no cure for HIV,’ said Dr Osamah Hamouda, who works with CHAIN at the Robert Koch Institute, a disease control and prevention research centre in Berlin. ‘But current antiretroviral therapy can slow, sometimes even stop, the HIV virus from replicating in the human body.’

Because lower concentrations of HIV in the blood stream also reduce the probability of transmission, these new drugs have helped cut global infection rates. And life expectancy for patients is on the rise.

The news is encouraging, but challenges remain. This rapidly mutating virus has a history of developing its own defences against treatments designed to stop it in its tracks. If the mutations it is capable of were to spread, the hard-earned achievements of the past decade would be completely neutralised. 

Dr Ana Abecasis. Image courtesy of L’Oréal.Dr Ana Abecasis. Image courtesy of L’Oréal.

At Lisbon’s Universidade Nova, Dr Ana Abecasis leads a new research group on the evolution of HIV that receives partial funding from CHAIN. Dr Abecasis, who in 2013 was awarded a L’Oreal Foundation research prize, is confident that the resilience of HIV does not make it invulnerable. ‘If the virus develops a resistance to one kind of drug, we can still counter it with a combination of the others. This may entail a pay-off in terms of the treatment cost or the quality of life of the patient, but it saves lives.’

The real danger, in Dr Abecasis’ view, is that drug-resistant mutations get transmitted. ‘The chances of an HIV virus simultaneously evolving immunity to three or more forms of treatment are low in new patients. But if a strain that is resistant to one kind of treatment spreads across a population, it could gradually develop resistances to the others.’

One of CHAIN’s objectives is to pool knowledge on drug-resistant HIV mutations by encouraging health services to upload the genomes of viruses identified in their patients into an international databank. By uploading such information, the databank can record the location of the patient associated with each HIV genome. The mathematical model then works backwards from the genetic and geographic records to identify how the virus strains branched out.

‘This recreates a family tree for the virus which helps identify how drug-resistant mutations were passed on,’ said Dr Abecasis.

The databank also includes records of which treatments worked against which mutations that offer guidance to researchers developing new drugs and help health services treating similar mutations elsewhere.

The rise of drug-immune HIV strains

Not all HIV mutations are dangerous to man. Some are actually lethal to the virus itself. But some of them present real risks.

‘HIV lacks the proofreading enzymes used by other living organisms to check that its genetic sequence is copied correctly during cell division,’ said CHAIN’s Dr Hamouda. ‘As a result, there tends to be a misreading in each replication cycle. Most of these mutations kill the virus. But those that survive could turn out to be more resistant to existing drugs.’

Scientific understanding of HIV mutations was significantly improved when mutation identification technology became a reality in the 1990s. ‘Before then, few hospitals were equipped to perform the Polymerase Chain Reaction required to detect them,’ explained Dr Hamouda. This technique artificially replicates the genome of the virus and identifies which parts of the DNA code have been corrupted.

Saving lives

‘Most of these mutations kill the virus. But those that survive could turn out to be more resistant to existing drugs.’

Dr Osamah Hamouda, Robert Koch Institute, Germany

Dr Abecasis, like many other researchers involved in the CHAIN network, travels regularly to conferences where results and ideas coming out of the initiative are exchanged. ‘The project has been helpful in focusing experts from so many different fields onto the problem,’ said Dr Abecasis.

Not all of these experts are scientists, the World Health Organization (WHO) is also part of the consortium, and many studies produced by CHAIN are designed to help guide policymakers in public health too. Its findings help to improve surveillance of drug resistance and influence national and WHO HIV drug-resistance strategies.

Dr Hamouda is conscious that his studies can not only shed light on the prevalence of drug-resistant HIV within a community, but can also offer valuable information to national health services on the urgency of conducting genetic tests during patient treatment.

Such studies can also identify vulnerable groups with particularly high rates of drug-resistant virus transmission, and this can focus prevention efforts. ‘The essence of what we are doing is translational science,’ said Dr Hamouda. ‘We are constantly translating what we learn from fundamental research into actions which can help patients.’

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