A four-year-old child who was said last year to have been "cured" of HIV after radical treatment with anti-viral drugs within hours of its birth has been found to be HIV positive – shattering the hopes that the virus could be vanquished.
Doctors in Mississippi confirmed yesterday that the child, who was born in 2010, now has detectable traces of HIV in its bloodstream and that there were signs that the virus was replicating once more within the toddler’s immune system.
A genetic analysis has confirmed that the strain of the virus is identical to the one that infects her mother, and scientists admitted that their earlier suggestions that the baby had been “functionally cured” of HIV were wrong.
The news is a setback in the 30 year struggle against HIV, which has now claimed the lives of about 25 million people around the world who have died of Aids-related illnesses. Since the virus was first identified in the early 1980s, some 60 million people have been infected with HIV, many of them resulting from maternal transmission at birth.
The child, known as the “Mississippi baby”, was the first reported case of prolonged remission of HIV infection following anti-retroviral therapy (ART) and the case raised hopes that the millions who currently take a daily cocktail of ART drugs might soon be able to stop their medications.
“Certainly, this is a disappointing turn of events for this young child, the medical staff involved in the child’s case and the HIV-Aids research community,” said Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases in Maryland.
“Scientifically, this reminds us that we still have much more to learn about the intricacies of HIV infection and where the virus hides in the body. The National Institutes [correct] of Health remains committed to moving forward with research on a cure for HIV infection,” Dr Fauci said.
The unnamed baby was born prematurely in a Mississippi clinic in 2010. Its mother was not herself diagnosed with HIV until the time of the birth – if she had been then she would already of been prescribed ART drugs to minimise the risk of HIV transmission during delivery.
However, given the late diagnosis of HIV in the mother, the doctors judged that there was already a high risk of maternal transmission and so it was decided to prescribe the newborn infant with liquid doses of three different anti-retroviral drugs – zidovudine, lamivudine and nevirapine – starting 30 hours after the baby’s birth.
Tests confirmed within a few days of birth that the baby had indeed been infected with HIV, probably during delivery. Doctors continued with liquid ART treatment and after two weeks the baby and mother were discharged from hospital.
Anti-retroviral treatment continued until the baby was 18 months old, when the child and mother went missing from the oversight of the local health services. Yet five months later, when the mother and child re-appeared, doctors found they could not detect any signs of HIV in the baby’s blood – down to a level of less than 20 copies of HIV per millilitre of blood, and with no HIV-specific antibodies.
More surprisingly, the child continued to be apparently clear of HIV and HIV antibodies for a further two years without any ART drugs. It was this that led scientists to announce last year that the baby had effectively been “functionally cured” of HIV – the first reported case of someone apparently eradicating the virus following ART.
In March 2013, for instance, Dr Fauci announced: “Despite the fact that research has given us the tools to prevent mother-to-child transmission of HIV, many infants are unfortunately still born infected. With this case, it appears we may have not only a positive outcome for the particular child, but also a promising lead for additional research toward curing other children.”
Even Françoise Barry-Sinoussi of the Pasteur Institute in Paris, who shared the 2008 Nobel Prize for the discovery of HIV in 1983, took heart with the case of the Mississippi baby. “[A functional cure] means people can be treated with drugs or whatever, and they will be able to stop their treatment and continue to control the virus without treatment. It is like remission in cancer,” Dr Barre-Sinoussi said.
However, during a routine visit to the clinic earlier this month, doctors found that the child, who is now four years old, has detectable levels of HIV in the bloodstream. From having levels that fell below the detectable limit of less than 20 virus copies per millilitre, the child’s levels had risen to 16,700 virus copies per millilitre.
In addition, the child’s immune system showed signs of being attacked. Levels of CD4+ T-cells – the white blood cells targeted by HIV – had fallen significantly and antibodies to HIV had re-appeared within the bloodstream.
This clearly indicated that HIV was replicating once more. However, the child is now responding well to ART drugs with no signs of side effects, according to the its doctors.
Despite the setback, Aids scientists hope that the case could still provide them with valuable insight into how HIV is able to hide from sight. It is well-known that the virus can integrate its genetic material into the DNA of a patient, but how it manages a long period of relative latency is still largely a mystery.
“The prolonged lack of viral rebound, in the absence of HIV-specific immune responses, suggests that the very early therapy not only kept this child clinically well but also restricted the number of cells harbouring HIV infection,” said Professor Katherine Luzuriaga of the University of Massachusetts Medical School.
Dr Fauci said that the early ART in the baby’s life may not have eliminated HIV completely but at least it seemed to have restricted the number of cells harbouring the infection, keeping the child clinically well.
“Now we must direct our attention to understanding why that is and determining whether the period of sustained remission in the absence of therapy can be prolonged ever further,” he said.