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BOSTON When scientists made the stunning announcement last year that a baby born with H.I.V. had apparently been cured through aggressive drug treatment just 30 hours after birth, there was immediate skepticism that the child had been infected in the first place.
But on Wednesday, the existence of a second such baby was revealed at an AIDS conference here, leaving little doubt that the treatment works. A leading researcher said there might be five more such cases in Canada and three in South Africa.
And a clinical trial in which up to 60 babies who are born infected will be put on drugs within 48 hours is set to begin soon, another researcher added.
If that trial works and it will take several years of following the babies to determine whether it has the protocol for treating all 250,000 babies born infected each year worldwide will no doubt be rewritten.
This could lead to major changes, for two reasons, said Dr. Anthony S. Fauci, executive director of the National Institute for Allergy and Infectious Diseases. Both for the welfare of the child, and because it is a huge proof of concept that you can cure someone if you can treat them early enough.
The announcement was the third piece of hopeful news in two days about the virus that causes AIDS.
On Tuesday, scientists reported that injections of long-lasting AIDS drugs fended off infection in monkeys, and on Wednesday, researchers announced a gene editing advance that might enable immune cells to repel the virus.
The first infant to make an apparent recovery from H.I.V. infection, now famous as the Mississippi baby, was described last March at the Conference on Retroviruses and Opportunistic Infections, the same annual meeting where the new case was reported on Wednesday.
The Mississippi child, now more than 3 years old, is still virus-free, said Dr. Deborah Persaud, a virologist who has run ultrasensitive tests on both children in her lab at the Johns Hopkins Childrens Center in Baltimore.
The second baby, a girl born at Miller Childrens Hospital in Long Beach, Calif., is now 9 months old and apparently free of the virus that causes AIDS.
Her mother, who has advanced AIDS and is mentally ill, arrived in labor; she had been prescribed drugs to protect her baby but had not taken them.
Four hours after the birth, a pediatrician, Dr. Audra Deveikis, drew blood for an H.I.V. test and immediately started the baby on three drugs AZT, 3TC and nevirapine at the high doses usually used for treatment of the virus.
Patients can live for decades with HIV infection as long as they take antiviral drugs that stop the virus from making copies of itself, known as replicating. But the virus is never gone. It lies dormant in a part of the immune system called resting memory T cells, making it basically invisible to the body’s defenses. However, “as soon as patients stop taking the drugs, the virus comes out of this latent state and starts replicating again,” said Johns Hopkins University HIV researcher Robert Siliciano. “That’s why you can’t cure anybody with the drugs.”
Doctors have hoped if they can decloak the virus while the patient is taking antivirals, the body’s own defenses would spot the infected cells and destroy them, and the drugs could keep the virus from spreading. But so far that hasn’t worked. One reason, Siliciano and colleagues write in the journal "Nature" the virus that comes out of hiding looks different than the one that caused the infection.
Master of disguise
HIV is a master of disguise, like a spy on the run. Secret agents can change their coat and color their hair, then they might duck into a closet until the coast is clear. Likewise, HIV is constantly mutating to evade the immune system. That's where the drugs come in. If the virus fools the germ hunters, called killer T cells, the antiviral drugs can still kill it. Except for the altered virus that has gone into hiding in the memory T cells. The new study found that when the virus comes out of hiding, nearly all of it is mutated -- still wearing a disguise that most of the killer T cells don’t recognize.
An HIV-positive patient rests at the Khmer-Soviet Hospital in Phnom Penh
Most, but not all, and that's the key. “Other cells see different parts of virus that have not mutated. Those cells can still be effective,” Siliciano said. There are fewer of them, and “they have to be stimulated in right way, but once they’re stimulated, they can recognize and eliminate those infected cells.”
Spot the shoes
Like training spy hunters to spot the secret agent’s shoes, Siliciano showed this smaller group of killer T cells a piece of the virus that had not changed. That stimulated them to find and kill most of the infected memory T cells. It’s good news, but it’s too soon to celebrate, Siliciano cautions. “Whether it would kill enough of them to allow a patient to go off treatment and not have the virus come back, we don’t know,” he said. National Institute of Allergy and Infectious Disease Director Anthony Fauci agrees. While the research shows a promising route to boost the body’s ability to tamp down the infection, he said, “I think it’s far too premature to be thinking that this a major step towards a cure, because getting a cure for HIV is going to be a very complicated, difficult thing that might not even be attainable,” he said.
Still, according to virologist David Margolis at the University of North Carolina at Chapel Hill, who was not involved in the research, it’s a brighter assessment than a study Siliciano published just a few years ago. “It painted a darker picture, like it would be very hard or impossible to get rid of latently infected cells,” Margolis said. According to the new research, he added, “it does look pretty straightforward to think of ways that we could re-target the immune response to clear that virus.” Siliciano said researchers may be able to develop a vaccine that would stimulate the killer T cells. Patients on antivirals would get the vaccine and then a drug to wake the sleeping virus.
Half the battle
A tiny fraction of HIV-positive adults holds the line against AIDS by mounting a very strong immune response; but, research has found that such an approach often contributes to the development of other illnesses, such as heart disease and cancers.
Kids look on in the Republican Hospital for Infectious Diseases, which specializes in treating HIV-positive children in Ust-Izhora outside St. Petersburg, Russia
Scientists at Oxford University looked at so-called pediatric non-progressors, the 5 to 10 percent of children infected with HIV who don't develop AIDS, even without treatment. Their study of 170 HIV-positive South African children revealed that their immune systems were behaving differently than adults'. Like non-human primates that harbor the simian version of HIV without becoming sick, there was very low immune activation even with high levels of the virus in their blood. Lead researcher Philip Goulder said, "(The) lack of HIV disease here seems to result from avoiding making strong immune responses against HIV."
Experts said the findings, published in Science Translational Medicine, could be the first signs of people co-evolving with HIV and eventually lead to new therapies for all patients infected with the AIDS virus.
Clues for Treatment From HIV-Infected Children Who Do Not Develop AIDS
