Gene therapy and new antiretroviral offer hope of better HIV treatment

Gene therapy, and the use of an experimental drug on monkeys, have shown promising results, with scientists cautious but optimistic

PUBLISHED : Thursday, 06 March, 2014, 9:37pm
UPDATED : Friday, 07 March, 2014, 2:30am

Two separate trials, involving gene therapy and the use of antiretroviral drugs, have shown promising results in the treatment of HIV.

In its first clinical trial, the radical gene therapy treatment, using genetically modified cells resistant to the virus, raised patients' defences against HIV by replacing some of their natural immune cells with GM versions.

Disease-resistant cells multiplied in patients' bodies. Half were taken off their usual drugs for three months and scientists recorded reduced levels of the virus.

Scientists who reported on the study yesterday in the New England Journal of Medicine were cautious not to draw strong conclusions from the small scale trial, designed to assess the safety of the therapy, but the early signs have raised their hopes.

"We are absolutely encouraged by these results," said Bruce Levine, who ran the trial with Carl June at the University of Pennsylvania in America. "This is potentially a new therapy for HIV."

Watch: What is HIV?

A few shots of modified immune cells, or perhaps even one large infusion, could become a future alternative for HIV patients who have to spend the rest of their lives on antiretroviral drugs. But Levine said any improvement in the patients' health would be welcome.

"Cure is a four-letter word. We don't like to use it, particularly with HIV. We are looking at improving the health and immune function of people with HIV," he said.

The therapy mimics a rare but natural mutation that makes about 1 per cent of the population resistant to the most common strains of HIV. To infect cells, the virus must latch on to proteins that poke up from the surfaces of the cells. But people with the mutation lack the right protein, called CCR5, so HIV cannot get inside their immune cells.

The trial centred on 10 men and two women, aged 31 to 54. All were HIV positive. The scientists began by collecting white blood cells from each of the HIV patients. They then modified the cells, so they carried the rare mutation that makes people resistant to HIV. They multiplied cells in the lab and infused a batch of 10 billion back into each patient.

Six patients were then taken off their usual drugs. As expected, the amount of HIV in their bodies began to rise. But as the freshly injected immune cells multiplied and circulated, they pushed levels of the virus back down.

Two patients were put back on their usual drugs early, because their HIV came back very quickly. But four showed improvements. In one, levels of HIV fell so low they could not be detected. The scientists later found out that he had inherited the rare resistance mutation from one parent, but not the other. "That effectively gave his immune system a head start," Levine said.

Some of the modified cells lasted several years into the trial, which has been running since 2009. All of the participants are now back on antiretroviral drugs.

Scientists have been excited about the prospect of genetically modifying patients' immune cells to make them resistant to disease since doctors effectively cured an HIV patient in 2008. Timothy Brown, also known as the Berlin patient, had a bone marrow transplant to treat his leukaemia.

Spotting their chance to treat both conditions, his doctors found a donor who carried the rare mutation that made their immune cells resistant to HIV.

Since the operation, Brown has had no detectable level of HIV in his body and no longer takes anti-HIV drugs.

In other research, success was also seen in the use of a single shot of antiretroviral drugs, which protected lab monkeys from HIV for weeks, according to a US trial that opens the way to tests on humans.

There are pills to prevent the infection only if people take them every day. In the monkey study led by Dr David Ho from the Aaron Diamond Aids Research Centre in New York, researchers injected 12 macaques with an experimental drug called GSK 744LA. They exposed them to the HIV virus weekly until the animals became infected. On average, the drug stopped working at the 10th week.

The researchers say the protection should last even longer in people, as monkeys clear the drug more quickly than humans.

Dr Chen Zhiwei, director of the University of Hong Kong's Aids Institute, said members of Ho's team would visit the city this month to discuss whether human trials would be conducted in Hong Kong and Shenzhen.

Ho chairs the institute's scientific advisory committee, and he received an honorary doctorate from the University of Hong Kong in 2008.

Additional reporting by Lo Wei