In medical first,baby with HIV is deemed cured; could change infant treatment line

The baby,born in rural Mississippi,was treated aggressively with antiretroviral drugs starting around 30 hours after birth,something that is not usually done. If further study shows this works in other babies,it will almost certainly be recommended globally. The United Nations estimates that 330,000 babies were newly infected in 2011,the most recent year for which there is data,and that more than three million children globally are living with HIV.

If the report is confirmed,the child would be only the second well-documented case of a cure in the world. That could give a lift to research aimed at a cure,something that only a few years ago was thought to be virtually impossible,though some experts said the findings in the baby would probably not be relevant to adults.

The first person cured was Timothy Brown,known as the Berlin patient,a middle-aged man with leukemia who received a bone-marrow transplant from a donor genetically resistant to HIV infection.

“For pediatrics,this is our Timothy Brown,” said Dr Deborah Persaud,associate professor at the Johns Hopkins Children’s Center and lead author of the report on the baby. “It’s proof of principle that we can cure HIV infection if we can replicate this case.”

The findings were presented at the Conference on Retroviruses and Opportunistic Infections in Atlanta on Monday. The results have not yet been published in a peer-reviewed medical journal.

Some outside experts said they needed convincing that the baby had truly been infected. If not,this would be a case of prevention,something already done for babies born to infected mothers.

“The one uncertainty is really definitive evidence that the child was indeed infected,” said Dr Daniel R Kuritzkes,chief of infectious diseases at Brigham and Women’s Hospital in Boston.

Dr Persaud and some other outside scientists said they were certain the baby — whose name and gender were not disclosed — had been infected. There were five positive tests in the baby’s first month of life — four for viral RNA and one for DNA. And once the treatment started,the virus levels in the baby’s blood declined in the pattern characteristic of infected patients.

Dr Persaud said there was also little doubt that the child experienced what she called a “functional cure”. Now two-and-a-half years old,the child has been off drugs for a year with no sign of functioning virus.

The mother arrived at a rural hospital in the fall of 2010 already in labor and gave birth prematurely. She had not seen a doctor during the pregnancy and did not know she had HIV. When a test showed the mother might be infected,the hospital transferred the baby to the University of Mississippi Medical Center,where it arrived at about 30 hours old.

Dr Hannah B Gay,an associate professor of pediatrics,ordered two blood draws an hour apart to test for the presence of the virus’ RNA and DNA. The tests found a level of virus at about 20,000 copies per millilitre,fairly low for a baby. But since tests so early in life were positive,it suggests the infection occurred in the womb rather than during delivery,Dr Gay said.

Typically a newborn with an infected mother would be given one or two drugs as a prophylactic measure. But Dr Gay said that based on her experience,she almost immediately used a three-drug regimen aimed at treatment,not prophylaxis,not even waiting for the test results confirming infection.

Virus levels rapidly declined with treatment and were undetectable by the time the baby was a month old. That remained the case until the baby was 18 months old,after which the mother stopped coming to the hospital and stopped giving the drugs.

When the mother and child returned five months later,Dr Gay expected to see high viral loads in the baby. But the tests were negative. Suspecting a laboratory error,she ordered more tests. “To my greater surprise,all of these came back negative,” Dr Gay said.

Dr Gay contacted Dr Katherine Luzuriaga,an immunologist at the University of Massachusetts,who was working with Dr Persaud and others on a project to document possible pediatric cures. The researchers,sponsored by amfAR,the Foundation for AIDS Research,put the baby through a battery of sophisticated tests. They found tiny amounts of some viral genetic material but no virus able to replicate,even lying dormant in so-called reservoirs in the body.

One hypothesis is that the drugs killed off the virus before it could establish a hidden reservoir in the baby. One reason people cannot be cured now is that the virus hides in a dormant state,out of reach of existing drugs. When drug therapy is stopped,the virus can emerge from hiding.

“That goes along with the concept that,if you treat before the virus has had an opportunity to establish a large reservoir and before it can destroy the immune system,there’s a chance you can withdraw therapy and have no virus,” said Dr Anthony S Fauci,the director of the National Institute for Allergy and Infectious Diseases. Adults,however,typically do not know they are infected right as it happens,he said.

Dr Steven Deeks,professor of medicine at the University of California,San Francisco,said if the reservoir never established itself,then he would not call it a true cure,though this was somewhat a matter of semantics. “Was there enough time for a latent reservoir,the true barrier to cure,to establish itself?” he said.

Still,he and others said,the results could lead to a new protocol for quickly testing and treating infants.

POSITIVE SIGN: AIIMS EXPERT

DR RAKESH Lodha,a paediatric HIV expert and associate professor in the department of pediatrics at AIIMS,said the report was “interesting”. “One cannot call it a ‘cure’ as there is still evidence of viral infection even though at an extremely low level. But from the observations,the virus does not appear to be replicating and that is a positive sign,” he said.

VIRUS LEVELS go down in many babies who get antiretroviral therapy,but the virus persists,he said. However,this does open a window of research opportunities to investigate this mechanism,and see if it can be replicated.

INDIA NUMBERS

OVER 1,00,000 children are thought to be living with HIV in India. Around 80,000 are registered at ART centres.

40,000 pregnant women test positive annually,and 12,000 children are born with the infection every year,according to NACO.