Study finds ‘setback’ in HIV fight
Thursday 24th October 2013, 5:10PM BST.
Dormant HIV that lingers in the body even after successful treatment poses a far bigger threat than was previously thought, research has shown.
The hidden virus reservoir may be 60 times larger than earlier estimates, according to the new findings.
The sleeping viruses, called proviruses, continue to be a danger because they can become reactivated despite treatment with the best HIV drugs.
Experts say the discovery, reported in the journal Cell, is a set back in the fight against HIV/Aids and highlights the fact that HIV infection can be treated, but not cured.
“The findings suggest that there are a lot more of these proviruses that we have to worry about than we thought,” said study leader Dr Robert Siliciano, from the Howard Hughes Medical Institute in Maryland, US. “It doesn’t mean that it’s hopeless, but it does mean we need to focus on getting an even clearer idea of the scope of the problem.”
In patients infected with HIV, the virus targets the immune system’s T-cells, where it is integrated into human genes.
The viral genes contain all the instructions to hijack the T-cell and turn it into a virus-producing factory.
But in some cells, the virus remains dormant. While sitting in the cell, it is not actively replicating.
Antiretroviral drugs can target active forms of the virus, but it is still unclear whether they are effective against inactive forms.
Until now, scientists did not have an accurate idea of how large the pool of dormant proviruses was.
“For people that are working on HIV, figuring out the size of the reservoir has been a really critical issue,” said Dr Siliciano.
“The field has struggled with what you even measure in people who are participating in eradication studies. How do you know how much virus is left?”
In the past, scientists have tried to gauge the size of the reservoir by forcing activation of the dormant viruses, or counting how many viral genomes – genetic code sets – were present. Neither approach provided accurate answers.
The new technique first involved stimulating infected T-cells, which sent a signal to wake up the inactive viruses. Those proviruses that remained inactive despite the wake-up call were then studied in more detail.
While 88% contained obvious defects that made it impossible for them to replicate, 12% possessed fully intact viral genomes.
Next, artificial viral genomes were made in the laboratory that matched those in the 12% group. The researchers expected to find small mutations that stopped these viruses functioning, but got a shock.
“To our surprise, the non-induced proviruses that we judged to be intact based on their genetic sequence all replicated beautifully,” said Dr Siliciano.
This suggests that many apparently lifeless proviruses could be activated in the future. Suspicions were confirmed when the scientists performed a second round of T-cell activation and viruses that had previously remained dormant became active.
Based on the finding that 12% of non-induced proviruses retain an ability to reactivate, the scientists calculated that previous estimates of the size of the dormant HIV reservoir were out by 60%.
“This is a huge increase in the barrier to curing this disease,” said Dr Siliciano.
Even if a patient was successfully treated with antiretroviral drugs that halted all active HIV replication, the silent viruses could awaken to cause disease at any point after the therapy is stopped. Only drugs targeting the inactive viruses could lead to a complete cure or remission, said Dr Siliciano.
The scientists’ next goal is to uncover the mechanisms involved in reactivating dormant HIV viruses.
Lisa Power, policy director at the Terrence Higgins Trust charity, said: “Prevention is not only better than cure; it’s also the only viable option we have for the foreseeable future.
“This study shows just one of the challenges researchers need to overcome. What is alarming is how many people believe a cure already exists. It doesn’t, and false hope may be leading people to take risks.
“Until a cure is found, we have to throw everything we’ve got behind HIV prevention. Using condoms, testing for HIV and getting treatment are our best weapons against the virus.”