HEALTH - Early Treatment of HIV Infants Works

"Early Treatment Is Found to Clear H.I.V. in a 2nd Baby" by DONALD G. McNEIL Jr., New York Times 3/5/2014

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 Children’s Center in Baltimore.

The second baby, a girl born at Miller Children’s 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.

The normal preventive regimen for newborns would be lower doses of two drugs; doctors usually do not use the more aggressive treatment until they are sure the baby is infected, and then sometimes not in the first weeks.

“Of course I had worries,” Dr. Deveikis said in an interview here.  “But the mother’s disease was not under control, and I had to weigh the risk of transmission against the toxicity of the meds.”

“I’d heard of the Mississippi baby, I’d watched the video,” she added.  “I knew that if you want to prevent infection, early treatment is critical.”

The Long Beach baby is now in foster care, she said.  The mother is still alive as well.

It is incorrect to describe the baby as “cured” or even as “in remission” because she is still on the drugs, Dr. Persaud said.  But because the most sensitive blood tests can find no virus capable of replicating, she describes the baby as “having sero-reverted to H.I.V.-negative.”

Both DNA and RNA of the virus were found in the baby’s early blood and spinal fluid samples, so Dr. Persaud said it was virtually certain she was infected at birth.  The virus began to disappear six days after birth and was undetectable within 11 days.

It is considered medically unethical to stop the baby’s drugs now, but Dr. Deveikis and Dr. Yvonne J. Bryson, a pediatric AIDS expert at the University of California, Los Angeles, who is also working on the case, said they would consider stopping them briefly to see what happens if the baby is still virus-free at age 2.

Dr. Bryson is one of three investigators who will lead the clinical trial seeking 60 babies.

Obstetricians and pediatricians in the United States, South Africa and Brazil will be alerted to watch for babies being born to mothers who have not taken drugs to prevent mother-child transmission and to get them on full antiretroviral treatment immediately, even before the first blood test has been finished.  (In the United States, fewer than 200 children each year are born with H.I.V.)

The trial will be funded by Dr. Fauci’s institute and be part of the Impact series of trials concentrating on preventing viral transmission to newborns.

“When we described the Mississippi baby, we were met with some skepticism,” she said.  The Long Beach baby “was definitely infected.”

The Mississippi baby was born to a mother who got no prenatal care and was unaware that she was infected.  Worried doctors at a local hospital transferred the baby to the University of Mississippi Medical Center, where a pediatrician, Dr. Hannah B. Gay, started aggressive antiretroviral treatment about 30 hours after birth.

Then, 18 months later, the mother stopped taking the baby to appointments and stopped giving the drugs.  Five months later, when she came to an appointment, doctors feared the baby would be teeming with virus.

Instead, to their astonishment, they found none.  And Dr. Persaud’s testing has found none, despite using tests normally able to detect dormant virus in adult patients on successful treatment.

Although antiretrovirals prevent the virus from replicating, a small amount usually persists in reservoirs throughout the body, integrated into the DNA of cells.  Dr. Persaud’s test can activate those cells and force them to “spit out” the virus, where it can be detected.

Dr. Steven G. Deeks, an AIDS expert at the University of California, San Francisco, said the Long Beach baby offered more convincing evidence that starting therapy virtually at birth seems to kill the virus before it establishes a permanent reservoir.

“But it sure would be nice to have a way to decide when to stop” the treatment, he added.  “That’s the next question.”