Next Steps for HIV Research After Toddler Functionally Cured

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http://www.medscape.com/viewarticle/780397

ATLANTA, Georgia — The headline-grabbing case of a 2-year-old child functionally cured of human immunodeficiency virus (HIV) is making international news and has delegates talking here at the 20th Conference on Retroviruses and Opportunistic Infections.
The case of a baby girl born with HIV and treated early with antiretroviral drugs who no longer has detectable levels of the virus, despite not taking medication for 10 months, has sparked widespread attention.
During an interview with Medscape Medical Newsafter the presentation that started it all, lead investigator Deborah Persaud, MD, from Johns Hopkins University School of Medicine in Baltimore, Maryland, cautioned that “this is a single unusual case." This baby was treated at 31 hours of age, probably the earliest an HIV-infected patient has ever been treated, “which we think has made the difference," she explained.

Dr. Deborah Persaud
However, “this is a hypothesis; it hasn’t been proven," she added. “Until the child is followed for some time and new data emerge, clinical practice should not change…. Pediatricians should tell parents that antiretroviral therapy is the mainstay of health for these children. They should continue on their antiretroviral drugs," Dr. Persaud noted.
The child in this case, born prematurely in July 2010, was delivered at 35 weeks to an HIV-infected mother who had not received antiretroviral medication or prenatal care.
Because of the high risk for exposure to HIV, the infant’s doctor started the newborn on liquid antiretroviral treatment consisting of 3 anti-HIV drugs — zidovudine, lamivudine, and nevirapine.
Antiretroviral Therapy
This child is reportedly the youngest newborn to be started on antiretroviral therapy.
The baby’s HIV infection was later confirmed in 2 blood samples analyzed with highly sensitive polymerase chain reaction testing.
The baby was discharged from the hospital at 1 week of age and placed on liquid antiretroviral therapy consisting of combination zidovudine, lamivudine, and coformulated lopinavir–ritonavir, the standard regimen in the United States for HIV-infected infants.
Plasma viral load tests performed on blood from the baby during the first 3 weeks of life also indicated HIV infection. However, by day 29, the infant’s viral load had fallen to less than 50 copies of HIV per milliliter of blood.
The baby remained on the prescribed antiretroviral regimen until January 2012, when she was 18 months of age.
In the fall of 2012, blood samples revealed undetectable HIV levels (<20 copies/mL) and no HIV-specific antibodies.
Undetectable HIV Levels
The child continues to thrive without antiretroviral therapy, and standard assays have found no detectable levels of HIV, Dr. Persaud reported.

Dr. Hannah Gay
She is under the medical care of Hannah Gay, MD, a pediatric HIV specialist at the University of Mississippi Medical Center in Jackson.
Dr. Gay told Medscape Medical News that she will continue to follow this patient and will treat others to see if the results can be replicated. “But this is not a signal that we can promise a cure," she said. “My advice to all infected patients who are on therapy is that if you are on effective therapy, please stay on your effective therapy."
Yvonne Bryson, MD, chief of pediatrics of the David Geffen School of Medicine at the University of California in Los Angeles, said Dr. Gay is “a hero who recognized how her patient needed to be treated and did it as part of her routine."

Dr. Yvonne Bryson
Dr. Bryson pointed out that in places in Africa, 30% of the women are HIV positive, but they don’t test babies until 6 weeks of age. She is working to change the recommendations in South Africa to identify newborns and retest them at 6 weeks.
Salim Abdool Karim, MBChB, PhD, from the Nelson Mandela School of Medicine at the University of KwaZulu-Natal in Durban, South Africa, agrees. “Is it doable in our setting? Absolutely. We have a very large proportion of babies being delivered in clinics and in hospitals. We could be starting them on antiretrovirals immediately after delivery," he said. “We have to face the breastfeeding problem and the risk of HIV transmission in breast milk, but in a nonbreast-feeding population, it is doable."
Landmark Event

Dr. Patricia Flynn
Patricia Flynn, MD, Arthur Ashe Chair in Pediatrics AIDS Research at St. Jude Children’s Research Hospital in Memphis, Tennessee, toldMedscape Medical News that this is a landmark event in the history of HIV.
“What is unique about this case is that the baby was treated very early. Unfortunately, the majority of the people who know that they have HIV infection have chronic disease, and we don’t yet have a functional cure for patients who have chronic disease," Dr. Flynn said. “The important thing is for us to keep an open mind and follow this baby to see what happens with time."

Dr. Lynn Mofenson
Lynn Mofenson, MD, chief of the Maternal and Pediatric Infectious Disease Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Maryland, emphasized in an interview that this is an individual case with some very unusual factors.
She pointed out that “the mother’s viral load was extremely low, even for someone who is not treated. The baby’s viral load at the first measurement was also relatively low for an infant with in utero infection. So it’s possible that this child really had intrapartum infection."
Dr. Mofenson explained that antiretroviral therapy within 24 hours is more likely to prevent disease establishment in a baby infected during the birth process than in one infected in utero.
“There are still a lot of questions to be answered about exactly how this happened," she said.
“I would not recommend that any clinician decide to stop antiretrovirals in kids that they’ve started treatment on. There are insufficient data to say that it’s safe and a lot of data to say that it’s not safe," Dr. Mofenson explained.
Dr. Mofenson clarified that this case “has nothing to do with adults…. Children don’t have memory T cells when they are born, so they lack that reservoir of availability; adults have a lot of memory T cells, which is where the residual HIV hides out. These are completely different situations."
Media Blitz

Dr. Howard Grossman
Howard Grossman, MD, an internist at AlphaBetterCare in New York City, told Medscape Medical News that “the mainstream press is treating this story as a cure, which is ridiculous. This is a very exceptional case from a scientific point of view, from a proof-of-concept, from trying to think about eradication. But it does not have any clinical relevance."
Dr. Grossman is concerned that the media are exaggerating the immediate clinical importance of this case, which “is going to create all kinds of drama in the exam room."
Clinicians can avoid this, he advised, by telling their patients that this is 1 individual case over a short period of time with results that are not well understood.
This is the first well-documented case of an HIV-infected child who appears to have been functionally cured.
A sterilizing cure has only been reported once, in an HIV-positive man treated with a bone marrow transplant for leukemia. The bone marrow cells came from a donor with a rare genetic mutation of the white blood cells that renders some people resistant to HIV, a benefit that transferred to the recipient.

In contrast to a sterilizing cure — a complete eradication of all viral traces from the body — a functional cure occurs when viral presence is so minimal that it remains undetectable with standard clinical testing.
This reseach was funded by the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Foundation for AIDS Research. Dr. Persaud, Dr. Gay, Dr. Bryson, Dr. Abdool Karim, Dr. Flynn, Dr. Mofenson, and Dr. Grossman have disclosed no relevant financial relationships.
20th Conference on Retroviruses and Opportunistic Infections (CROI): Late-breaking abstract 48. Presented March 3, 2013

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