A newly-developed HIV therapy stops the virus’s replication and may provide what the researchers call a ‘functional cure’ to the devastating disease.
Scientists at the Scripps Research Institute in Florida announced Tuesday that their new drug may reduce an infected person’s viral load so far that HIV can no longer spread to healthy cells when used in combination with the current recommended cocktail of antiretroviral drugs.
This discovery comes one month after the Centers for Disease Control and Prevention (CDC) announced that once the viral load of HIV is reduced below the level of being ‘detectable,’ it is effectively no longer transmissible.
After the researchers injected the drug into mice, the virus stayed below the detectable level more than twice as long as it did with just the standard cocktail, indicating that the treatment may have lasting effects.
Scientists at Scripps Research Institute have developed a new therapy that they say may one day be a ‘functional cure’ for HIV, if it proves as effective in humans as it has in mice
The Scripps study uses a totally new approach that lead author Dr Susana Valente calls ‘block-and-lock.’
She and her team came up with a new drug compound called didehydro-Cortistatin A (dCA) in the Scripps lab in Jupiter, Florida.
After the viral load of HIV has been reduced down to undetectable levels by the traditional cocktail of medications, dCA prevents infected cells from reactivating and copying themselves, the mechanism by which the virus spreads.
The drug then ‘locks’ the HIV virus into a dormant state, which, from the study’s results could suppress it for as much as 19 days. The virus began to replicate again after only seven days in the mice that were only given the standard antiretroviral cocktail.
Antiretroviral therapy would still be necessary, but maybe not daily, and maybe not forever
The current standard treatment for HIV is not a cure, and even if it works as well in humans as it does in mice, patients would still have to take it with the standard treatment in order for it to be effective. It is not a replacement for antiretroviral therapy.
Though there are variations, treatment typically involves a combination of three antiretroviral drugs designed to prevent HIV from reproducing in the body of an infected person, combined into one pill.
This ‘cocktail’ has to be taken every day, for the rest of one’s life, in order to be effective. If it is effective, it can reduce the amount of HIV in a person’s system – their ‘viral load’ – to an undetectable level, which, per the CDC’s announcement, effectively means that it cannot be transmitted to an uninfected partner.
The treatment is widely effective, but for about one in six people, their first regimen does not work. If the first one-year round of treatment is effective, the odds that it will continue to work go up with each following year.
Current therapies also come with a host of long and short term side effects. Antiretroviral therapy can cause nausea, vomiting, diarrhea, fever, fatigue and muscle pain, among other side effects, in the short term.
The coolest thing about this drug is that it really can reduce the virus to very, very low levels, and if we understand it better, we may get to a point where it’s so hard to reactivate and you can be drug-free for a while
Dr Susana Valente, HIV researcher at the Scripps Research Institute
Long term use can damage the kidneys and liver, lead to heart disease, diabetes, weaken the bones and cause weight gain and psychiatric issues like insomnia and depression.
But HIV becomes resistant to treatment in some people. Missing even one day of the drugs could also allow the virus to come back in full force and undermine the effectiveness of treatment.
Dr Susana Valente, the lead author for the new study, says that the dCA therapy has the potential to suppress the HIV virus for longer periods of time, so that one missed pill may not disrupt treatment so badly.
‘Over time, it might have a nice impact on the size of the reservoir [of HIV-infected cells], to a point that maybe even just the immune system could [suppress the virus] on its own,’ she says.
The researchers are a long way off from being able to prove that, but dCA does have promisingly durable effects on viral load.
How dCA kills the engine in HIV
The dCA therapy targets a protein called tat, which is a powerful activator for the process of copying the HIV virus.
‘Tat, it’s like fuel for this car. Once the virus is our genome…tat is like a turbo engine, it really turns on that transcription,’ says Dr Valente. She says while scientists have long known how important tat is to HIV’s spread throughout the body, they haven’t known how to stop the protein.
But dCA does exactly that. Dr Valente and her team gave mice infected with human HIV cells antiretroviral therapy (ART) and dCA every day for just one month.
The virus was reduced to be undetectable. The dCA kept the viral cells from reproducing, even more than two weeks after the researchers stopped administering the drug.
Eradication is what we really want, but a functional cure may more realistic.
Dr Susana Valente, HIV researcher at the Scripps Research Institute
By itself, ART keeps the virus repressed, but there is still a ‘trickle’ of HIV RNA, which allows it to continue to be copied, says Dr Valente. The new therapy eliminates the risk posed by that ‘trickle.’
‘The coolest thing about this drug is that it really can reduce the virus to very, very low levels, and if we understand it better, we may get to a point where it’s so hard to reactivate and you can be drug-free for a while,’ Valente says.
She says that the drug basically made HIV’s engine, tat ‘rusty,’ and, for the first time, after the drugs were stopped, there was not an immediate viral rebound.
But, of course, it doesn’t eliminate the need for ART, so it dCA is not an eradication but a functional cure.
Finding a realistic kind of cure
‘Eradication is what we really want,’ says Dr Valente, ‘but a functional cure may more realistic.’
She adds that other strategies in development could eventually target and destroy the virus in every single cell, effecting a cure, ‘but that’s a harder task.’
Tat is also responsible for some of the neurological symptoms of HIV, she says. So dCA could help to restore, or at least prevent the progression of problems with motor skills and memory for those with HIV.
Dr Valente is audibly excited about her team’s discovery, but Dr Carl Dieffenbach, director of the AIDS division of the National Institutes of Health (NIH) says that it’s ‘very early days’ in the research process of dCA.
NIH funded this and many studies on HIV. Dr Dieffenbach says that this discovery is part of the next wave of innovation in HIV therapies, and ‘a step along the way,’ but it’s too soon to tell how effective it will be for treating HIV in humans.
He says it’s also unclear how different from or superior to other therapies in development this one is. ‘What we’re continually seeking are improvements that are as safe as the current one, with better outcomes,’ he says. ‘
‘If you could demonstrate in clinical studies that that is what [the Scripps researchers] have here, I think the HIV positive community would be receptive to it.’