Several reports being presented to coincide with an international AIDS conference this week may at first raise hopes that it could be possible to cure HIV infection. But two other major developments make it clear that it’s pretty much back to the drawing board for researchers trying to find a way to thwart the virus.
In one report, researchers at St. Vincent’s Hospital and the Kirby Institute in Sydney, Australia, say two men who got bone marrow transplants to treat their cancer appear to be free of the virus. In another, Canadian researchers say four babies treated right after birth show no sign of the virus, either.
But recent U.S. findings have poured cold water on the idea that any of the patients will escape the virus for long. And a new study presented at the conference on Monday may help explain why.
“Those Australian patients are still on (HIV) therapy,” said Dr. Anthony Fauci, head of the U.S. National Institute for Allergy and Infectious Diseases. The drugs may be suppressing the virus, Fauci told NBC News. “Just because you can’t find it that doesn’t mean it’s not there.”
The human immunodeficiency virus that causes AIDS attacks the immune system. That’s what makes it so hard to fight—it infects the very cells that the body sends out to fight invaders like viruses. Like all viruses, HIV hijacks the cell and forces it to pump out copy after copy of virus until it dies.
Scientists have invented two dozen different drugs that can slow down the virus, and people who take a cocktail of the drugs can seem uninfected. Drug therapy can even drive the virus down to undetectable levels.
But the virus finds somewhere to hide. No one knows where, but almost invariably, if people stop taking the drugs, the virus turns back up after a while. It happened earlier this year in the so-called Mississippi baby, who was infected at birth and treated with a strong cocktail of HIV drugs right away instead of the usual lighter dose given to newborns of infected mothers.
She seemed cured, but disappointed doctors reported earlier this month that the child, now just shy of 4, is indeed infected.
A similar disappointment happened late last year with two U.S. men who got bone marrow transplants for cancer. They looked like they may have been cured, but turned out to still be infected.
The only person with a documented cure is Timothy Brown, also known as the "Berlin patient," who was treated for leukemia with a bone marrow transplant that happened to come from a donor with a genetic mutation that makes immune cells resist HIV infection. The transplant replaced Brown's own infected cells with healthy, AIDS-resistant cells, and he remains free of the virus more than five years later.
Doctors had hoped that if patients got bone marrow transplants while taking HIV drugs, the virus would not be able to take hold in the freshly transplanted bone marrow cells - which are the source of new blood cells. Dr. Daniel Kuritzkes of Brigham and Women’s Hospital in Boston, who treated the two U.S. men who had hoped for a cure, says he is still looking for patients. “It’s not a reason to give up research on a cure,” he said.
Dr. Ari Bitnun of Toronto's Hospital for Sick Children, who is treating five Canadian children infected at birth, is also not giving up hope. Four of the babies treated at birth are still free of detectable virus, and one is eight years old. But they’ve all continued to take HIV drugs the whole time. A fifth child was taken off the drugs and the virus came back, just like in the Mississippi baby. "It may be that it will work for some babies and it won't work for others,” Bitnun told reporters in May.
A study released at the AIDS conference and published in the journal Nature may help explain why. It’s in monkeys, which cannot be infected with human AIDS but which can get a similar virus called SIV. Dr. Dan Barouch of Beth Israel Deaconess Medical Center and colleagues infected 20 monkeys with SIV and gave them HIV drug cocktails at between three and 14 days afterwards – simulating what happened with the babies.
In the monkeys treated as quickly as three days after infection, there was no detectable immune response to HIV and no evidence of the virus in their blood. But DNA from the virus could be found in cells of the gut and lymph nodes in all of the monkeys. As soon as treatment stopped, the virus reappeared in all the monkeys, including those treated at three days.
That suggests the virus finds a good hiding place almost immediately, say Dr. Robert Siciliano and Dr. Kai Deng of Johns Hopkins University. “These data indicate that the viral reservoir could be seeded substantially earlier than previously assumed— a sobering finding,” they wrote in a commentary on the findings.
One new piece of hope comes from a team at Temple University School of Medicine, that developed a way to cut HIV out of the cells it infects. They only performed the work in lab dishes – a long way from doing something in a living animal, let alone a person.
But their method excised the virus from the cells, allowing the cells to heal, they reported in the Proceedings of the National Academy of Sciences. "This is one important step on the path toward a permanent cure for AIDS," Kamel Khalili, chair of the Department of Neuroscience at Temple, said in a statement.
They combined an enzyme called a nuclease, which cuts apart DNA, and a programmed strand of genetic material called a guide RNA. The guide RNA found the HIV and the nuclease snipped it out.
"We want to eradicate every single copy of HIV-1 from the patient. That will cure AIDS. I think this technology is the way we can do it,” Khalili added.
The approach is similar to gene therapy, a technique that has only a spotty history of success after more than 15 years of human trials. It’s very hard to deliver such technology to every cell in the body, for one thing, and it’s not clear the guide RNA could hunt down HIV in its hiding place.
Researchers speaking at the AIDS meeting in Melbourne tried to play down expectations.
"I don't know how long it will take to get a cure," said Francoise Barre-Sinoussi, the French virus expert who is credited with discovering HIV, told the conference.
"My personal opinion is that if it is possible, and we can do it, it's going to take many, many years,” Dr. Steven Deeks of the University of California, San Francisco, told reporters.