HIV cure is a tough ask
DW: We've had antiretroviral drugs for a number of years now, but we're still looking for a cure. Why do we need a cure for HIV?
Professor Sharon Lewin: I think there are three main reasons why we need a cure. The first is that treatment isn't perfect. Treatment makes people much better and makes them live longer, but life expectancy is still not back to normal in a large number of patients, and there are ongoing toxicities and side-effects from the treatments. Then, I think the real issue is the cost of treating all the people who need it lifelong. It's estimated there are 15 million people who need antiretroviral treatment and we're treating about 60 percent of them. And we're struggling to even maintain that - let alone treatment for the next 40, 50 or 60 years. So, I see a really strong economic argument for a cure. And if you speak to people who are infected, patients see this as a really high priority, so they can stop their drugs. What most patients want is a sterilizing cure - to no longer be HIV-positive. A sterilizing cure could be a tough ask in HIV - I'm not sure we're going to be able to achieve that, but there's a real patient desire for a cure. So, the other option is a functional cure, which means the virus is still there but at very low levels, and the patient's able to keep it under control in the absence of treatment.
You've been looking extensively at latency of the virus - its lying latent, or dormant. Why is learning about that so important?
HIV likes infecting a type of immune cell called the T-Cell, and it does different things in different T-Cells. So, in some T-Cells it replicates and divides..., you put people on treatment and it wipes out that part of the virus. But it has this very clever trick, which is called latency, where it gets into a resting cell, becomes part of the patient's DNA and effectively lies dormant. But it is still able to be infectious. These "infected-sleeping cells" or "latently-infected cells" are quite rare. But it's as if you've got these burning embers that are always there and the minute you stop the drugs the whole thing gets going again.
And you've found a way of reawakening these latent cells…
Yes. The fact there's a persistent virus in latently-infected resting cells is the main reason why current treatments don't cure HIV. Because once you stop the drugs, those resting cells wake up and the whole thing gets going again. So, we're very interested in knowing how we can get rid of those latently-infected cells. One way that's being tested now is to wake up that virus, so that it becomes visible to the immune system. Or by waking it up the cell could possibly self-destruct and you could wipe out those last bits and pieces of virus that hang around.
Is there not a risk factor in waking up the virus?
Well, we're thinking this will work only in people who are on treatment - they have to be on effective anti-HIV drugs. So, the idea is you wake up the virus, the virus is released from that cell, and it's got nowhere to go because you're on anti-HIV drugs. And the anti-HIV drugs stop the virus from hopping into the next cell. We've just done this clinical trial of a drug that does exactly this and we were quite concerned the virus would go crazy when we woke it up. And we explained all this to our patients because at the time we didn't know… And as it turned out, the virus didn't go crazy. With the usual tests we use, we could only detect a smidge of the virus in the blood in three out of the 20 patients, and it was at very low levels. Are there other adverse events from using these medications? There are. These drugs we're using are currently for cancer, so they're for people who have a very serious, life-threatening illness, and we know there are side-effects from these drugs. But we don't know whether there are any long-term consequences of taking them for at least two weeks - we're going to watch the patients very closely.
We were talking earlier about antiretroviral drugs and how access to them is improving. And I think access is also increasing in regions like Sub-Saharan Africa. What would you see as the best development in Sub-Saharan Africa and other poorer regions while your research continues? What needs to happen?
Our researching a cure can't get in the way of access to treatment because that's absolutely fundamental. Treatment works and it saves lives, it stops new infections. But at the moment, we're treating 60 percent of people who need treatment, so we need to do better… I think what's happened in Africa is incredible. Back in 2000, there was no-one on antivirals and most of the community thought it'd be too hard, too expensive, too complicated. And that was not the case. There's now 11 million people on treatment in countries that have health systems where people thought they wouldn't be able to support the complexity of anti-HIV drugs, but they've done brilliantly. South Africa last year had 20 percent fewer new infections than the year before, which is amazing. And it's probably largely due to more and more people being on treatments, so there's less virus in the community. Botswana is another amazing success story - about 80 percent of people who need treatment are on treatment. Cambodia is another great success story. But it's hard work. It needs a lot of ongoing investment, training and capacity building. Access to testing is vital as well. So many people don't even know that they're infected. We have a lot of work to do in many countries to strengthen health systems, to find people, test them, and keep them in care.
Professor Sharon Lewin is the director of the Infectious Diseases Unit at the Alfred Hospital in Melbourne, Australia. She also heads the Department of Infectious Diseases (DID) in the Central Clinical School at Monash University.