HIV's genetic hiding place discovered | Innovations

HIV's genetic hiding place discovered

HIV's genetic hiding place discovered

Updated 12 March 2013, 10:36 AEDT

How scientists have figured how to make the HIV virus wake up from its hiding place with a strategy known as 'shock and kill'

 

DESLEY BLANCH :  The search for a cure for AIDS has taken another step with Australian researchers in Melbourne uncovering HIV’s genetic hiding place. A team from The Alfred hospital has used a cancer drug to turn on sleeping HIV-infected cells so they could be detected and measured so they can be destroyed.

The Alfred Hospital’s director of infectious diseases is Professor Sharon Lewin who took my call in Atlanta in the United States on the eve of presenting their findings to the world’s leading HIV experts.

PROFESSOR SHARON LEWIN : We are very excited about the findings but it really is only one small step in what is going to be a major challenge in ultimately curing HIV.

So we currently have excellent treatments for people with HIV. Many people can literally take one tablet a day and keep the virus under control and the life expectancy for most people who take tablets now is almost the same as an HIV-negative person. So once they stop medication the virus basically comes straight back out in the blood within about two to three weeks.

And for many years we’ve known the virus hides in certain places and it actually hides by burying itself deep inside the patient’s DNA so it becomes part of the patient’s own genetic code. And it hides there and basically invisible to the immune system and invisible to drugs and that’s the big challenge of finding a cure; getting rid of the virus that hangs around in the inviting cell.

So what we did in our study was and what many other researchers are thinking about doing, is waking up the virus from where it hides inside the body and once it wakes up, the idea is that the immune system can then see the virus or drugs can see the virus and that infected cell could be eliminated.

And we did this recently in the trial that I’ll be presenting tomorrow here in Atlanta where we gave 20 patients all who were very well on anti-HIV drugs for many years, with what we call undetectable virus in their blood and  a normal immune system and gave them the drug that’s normally used to treat cancer but we know can wake up this sleeping virus at least in a test tube.

And we gave the patients the cancer drug for 14 days and found first of all, that it was safe in patients and all 20 patients completed the 14 days of treatment, and second, that the drug indeed did wake up the sleeping virus in 90 per cent of the patients who took the drug.

DESLEY BLANCH : This is a very strong cancer drug that you used to wake up that virus wasn’t it?

PROFESSOR SHARON LEWIN : It is a drug that’s now used to treat a rare form of skin cancer. It’s actually a member of a new class of drugs that have been used for treating cancer, and yes, these drugs have many unknowns; although the drug has been in thousands of people with cancer so we know what the short term side effects are.

We actually don’t really know what the long term side effects are. So participants in this study were certainly very brave and highly motivated to participate, because there were some unknowns about the long term safety of this drug, which is why we gave such a short course of only 14 days.

DESLEY BLANCH : And it woke it up in 18 of 20 HIV patients?

PROFESSOR SHARON LEWIN : It did, yes. We can measure whether the virus wakes up by looking inside a cell to see if we can find virus genetic code there and yes, we could detect it in 18 of 20 patients. This didn’t mean the virus went away, it just told us the virus could be woken up.

DESLEY BLANCH : And so once you wake it up you’ve then got to kill it off. Do you have a drug yet in existence that can kill it off or is that yet to be invented?

PROFESSOR SHARON LEWIN : Yeah, this whole strategy is often referred to as “shock and kill”, so you shock the virus out of its hiding spot and come in and kill with a different agent.

There are a number of ideas of what might kill the cell and that could include a kick start to the immune system with a vaccine, for example, or there are other drugs that can also boost the immune system that work slightly differently to how a vaccine works or maybe we just need to give more of the Vorinostat drug or relatives of the Vorinostat drug; that’s what we need to answer in the coming years.

DESLEY BLANCH : Well, you’re results are from strong Australian research amongst Melbourne-based institutions. You’ve got the Peter MacCallum Cancer Centre, Monash University and your Burnett Institute. So what’s your message for those people living with HIV, what will it mean for those people living with HIV?

PROFESSOR SHARON LEWIN : This is the first step in what will be a big complicated challenge to ultimately find a cure but I think there’s a lot of interest and energy around doing this amongst scientists and they’re certainly an increased interest amongst funders and governments to really accelerate our path towards finding a cure.

So my message is it’s not going to be next week or next year, it may take many years, but there are many, many scientists and clinicians now committed to finding a cure.

DESLEY BLANCH : They are 4.2 million people living with HIV in Asia. Our listeners are in Asia and the Pacific. So what are the challenges in Asia that are quite different from other parts of the world where HIV’s concerned?

PROFESSOR SHARON LEWIN : One big challenge is getting access to treatment when you need treatment, that should and is the main priority for all funding agencies: that people that need treatment must get access to treatment, because we know treatment works and treatment saves lives and prolongs life. And we know currently in low income countries across the world including in Asia, roughly 60 per cent of people who need treatment are on treatment. So that should be our number one priority.

A big advantage of treatment is that it not only makes a big difference to the patient’s health but it reduces their infectiousness by 96 per cent, so the more people who are on treatment means the less likely we’ll get transmission of the virus.

However, my big unique challenge for Asia is the diversity of the epidemic. In some countries it’s predominantly in injecting drug users, in other countries it’s in men who have sex with men or commercial sex workers and often these groups are marginalised and don’t often have access to good healthcare services.

So it’s getting the message out to those groups, making sure that they have access to health services and that there is no stigma and discrimination based on they’re being HIV infected. They are challenges all across the world but I think they’re particular challenges within Asia.

DESLEY BLANCH : Sharon, next year, the AIDS Conference will be held in Melbourne, Australia, of which you are a local co-chair. It’s ten years since this conference has been held in Asia-Pacific so what will be the focus of the conference in helping those with AIDS/HIV in this region of the world?

PROFESSOR SHARON LEWIN : Yeah, well we’re very excited to be hosting the conference in Melbourne. It’s actually the first time it’s ever been in Australia and will be the biggest medical conference ever to come to Australia. And as you say, it was in Bangkok ten years ago.

It’s a global international meeting and the focus of the meeting will certainly be on the global challenges in HIV which is first and foremost access to treatment and preventing new infections. But there will be a very strong focus on the issues that are prevalent in Asia.

DESLEY BLANCH : Well, given your latest advance, how optimistic are you about a future HIV/AIDS therapy and perhaps cure?

PROFESSOR SHARON LEWIN : It’s really hard looking ahead to know when we will have a cure. What I do know is that the HIV virus is incredibly smart and although we have conquered various aspects of the virus, there are many tricks that the virus has up its sleeve that we discover and you just have to look at how hard it’s been to develop a vaccine which we still don’t have.

But when I look back over the last 30 years and see how much we’ve learnt and what an incredible change to peoples’ lives we’ve witnessed, where 30 years ago HIV was a universal death sentence and now it’s a completely manageable chronic disease where people can have a normal life expectancy.

It’s incredible how the science has moved and how communities have managed to galvanise the pace of research. So I have some optimism that we’ll see a lot of advances in the next 30 years. Whether we see a cure in that time I don’t know; I think it still will be very, very difficult to find but we’re making some small steps now which is very exciting.

DESLEY BLANCH : Professor Sharon Lewin is director of Infectious Diseases at The Alfred Hospital in Melbourne and it was Sharon and her team who only last year were the first to uncover how the virus hides dormant in infected cells and out of reach of conventional treatments and the immune system.

 

Contributors

Sharon Lewin

Guest

Co-head at the Centre for Virology and NHMRC Practitioner Fellow at the Burnet Institute

and Director of the Infectious Diseases Unit at The Alfred Hospital, Melbourne 

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