In March of last year, at the 20th Conference on Retroviruses and Opportunistic Infections (CROI) in Atlanta a group of researchers announced that a child in Mississippi with viral control post-antiretroviral therapy (ART) had been cured of HIV. The story took the media by storm, with headlines in the New York Times, CNN, and PBS’s News Hour, among other places. But some experts were skeptical and asked whether the results had been released prematurely.
Was the Mississippi baby really “cured” of HIV? In order to better understand the case, it is important to define what a cure entails in the field of HIV research. An eradication cure, sometimes referred to as a sterilizing cure, involves completely eradicating HIV-infected cells from the body so that the virus is no longer present. The only example of what experts consider an eradication cure is “the Berlin patient,” reported in 2009. The patient, Timothy Brown, received a stem cell transplant from a donor who had a genetic mutation that protects the immune system from the HIV virus. Since then, Brown has shown no signs of HIV and been off treatment for six years. The Mississippi baby, on the other hand, is an example of a “functional cure” which involves treating individuals so that the virus decreases to such levels that it does not cause disease within an individual and can be controlled without continued antiretroviral treatment. In this scenario, “the immune system or some other mechanism” keeps the virus suppressed.
The Mississippi baby’s functional cure came about almost by accident.
The Mississippi baby’s functional cure came about almost by accident. The infant was born to a mother who had not been diagnosed before birth—the optimal time to prevent HIV transmission from a mother to child. As a result, her baby was started on a more aggressive three-drug therapeutic antiretroviral treatment regimen at 30 hours of life rather than a more typical prophylactic regimen. After starting treatment the child’s viral load came down. The mother missed scheduled appointments for her child at 18 months. When she came in five months later, she reported that the child had not been on treatment since the last visit. Yet tests showed the child had no detectible viral load even off of the antiretroviral treatment.
A year later at the 21st CROI in Boston, Dr. Deborah Persaud presented follow up information on the Mississippi baby, who was now 41 months of age and had been off ART for almost two years with no rebound of HIV.
The authors also reported on a second infected child who was started on treatment at four hours of age. Like the Mississippi baby, blood tests did not detect replication of HIV, but the child remained on antiretroviral treatment. It is too early to tell if the child is functionally cured.
What does this case of “functional cure” mean for the field? Should treatment be initiated in all HIV-infected infants at birth in order to achieve the outcome of the Mississippi baby? A recent review that Dr. Louise Kuhn and I published in Expert Review of Anti-infective Therapy highlights some important issues in the care and treatment of HIV-infected infants and children raised by the Mississippi baby.
Current World Health Organization treatment guidelines recommend that treatment be started in all children under five years old regardless of clinical signs and symptoms and immunologic status. However, these recommendations do not inform whether or not treatment should be started as early as birth.
Though starting treatment at birth may bring the possibility of functional cure and other benefits for infants, there are diagnostic challenges. Early initiation of ART depends on early diagnosis of HIV-infected infants, which will require a shift to routine diagnosis at birth. HIV testing will have to occur not only at birth to detect infections that occur in utero but again later to detect infections that occur during delivery and in the early postnatal period. There also are limited safe and effective treatment formulations available for newborns.
Though the case of the Mississippi baby has brought optimism around the possibility of a “functional cure” in HIV-infected infants, more research is needed. In the meantime, providing treatment for HIV-infected children who are not receiving it should continue, and prevention of mother to child transmission should remain a priority.
Edited by Louise Kuhn and Elaine Meyer