Until a few years ago there was no talk of curing HIV. Research focused on making anti-HIV drugs better, trying to find a vaccine or understanding why they didn’t seem to be working. Another area was public health - trying to encourage sexual behaviour that could prevent the spread of HIV, though this hasn’t been altogether successful - it would seem we are just a species that likes to take risks.
Recently though there seem to be more reports that a cure is just around the corner or even inevitable. There was the report that a baby was successfully “cured” with anti-retroviral therapy drugs and soon after 14 adults - the “Visconti cohort”.
Despite talk about cures anti-retroviral therapy, also known as ART, has been one of the great medical breakthroughs of the past century. The ability to inhibit how the virus replicates to the point where someone who is HIV positive can live as long (or not far off) as someone who isn’t has changed lives across the planet.
HIV integrates itself into our genes and becomes latent, which means it effectively goes to sleep, before waking up to kick off the infection at an unpredictable time.
While someone with HIV is taking ART drugs, there are probably around a million of these sleeping HIV-infected cells hidden throughout the body. The ART drugs don’t touch this reservoir of infection, which is why they have to be taken every day for life so there are drugs in the body whenever the virus might choose to wake up.
The parallel is with a cancer in remission, where one or two malignant cells can erupt unpredictably causing a full-blown return of the cancer even if treatment looks like it has been successful.
The ‘Berlin patient’
In 2008 the report that Timothy Brown, a HIV-positive man with leukaemia, had been successfully treated in Berlin using a “HIV resistant” stem cell transplant that subsequently cured him of both diseases changed the landscape.
Then in March this year came the news of the newborn baby that had also been cured, but this time by treating with standard ART drugs very early (within 30 hours of birth). News of the child in Mississippi spread quickly.
And just as the excitement of the Mississippi child was abating, a group of French researchers announced that 14 adults had been cured. ART had been started shortly after infection and then continued for many years. When these patients stopped their drugs, the virus – not sticking to the script – did not come back.
There are still more questions than answers concerning the Visconti cohort, but there is a striking lack of evidence supporting a critical role for the immune system in “post-treatment control”. It’s a fact that will trouble supporters of vaccines.
Where does this leave us? With the huge global scale of HIV, not really any further on. At a global level, policy must focus on getting therapy to all those who need it and keeping HIV negative individuals uninfected.
Currently in the UK, around one quarter of HIV positive individuals are unaware they are infected and therefore aren’t seeking therapy, and there are still around 6000 new diagnoses each year.
Hardcore virologists who study the disease will still insist that curing HIV is impossible. But there is a growing body of researchers who feel that our current strategies – although successful at stemming the tide of death and illness that had characterised AIDS in the 1980s – may not be adequate over the next ten, 20 or 50 years.
Apart from the risk of toxicities and drug resistance, current therapy is expensive - although non-branded generic drugs may bring prices down. But the main hurdle is that therapy is for life and treatment fatigue is a major problem.
The Berlin patient, the Mississippi baby and the Visconti group studies are encouraging and reveal that there may be potential chinks in HIV’s armour. That cures might have been achieved through such different approaches indicates that the reservoir is susceptible to attack.
A three-pronged attack
By understanding that HIV was behaving like a cancer, a new class of HDACi drugs is now being trialed in patients with HIV. One of these - Vorinostat - can “wake up” latent cells in the reservoir, but no suggestion yet that they can be killed. We need considerably more data before this might be translated into a cure. Unfortunately, in a news interview (which was subsequently re-worded online) with scientists from Denmark, an incomplete trial of a different HDACi - Panobinostat - was described as possibly leading to a cure within months - despite no data being presented.
These are very early days – no one should have any false beliefs about this. The aim of any research is still to prove that a cure for HIV is worth studying and investing in. We learnt in the 1990s that successful HIV therapies had to be combinations of drugs. The same will be undoubtedly true for any cure. The next step, and possible game changer, will be a three-pronged approach combining ART, to keep the virus at bay, an HDACi to wake up latent cells, and a vaccine - work currently being proposed by the CHERUB collaboration in the UK.
The big challenge now is to define a strategy that can be scaled up to treat larger populations than just focusing on cures.