'Mississippi Baby' Thought 'Cured' of HIV Relapses

Mark Crane

July 10, 2014

The child known as the "Mississippi baby," an infant girl who was believed to be cured of HIV, now has detectable levels of the virus after 27 months of not taking antiretroviral therapy without any evidence of the virus, pediatric HIV specialists and government researchers said today.

The discovery that the virus had rebounded was made during a routine clinical care visit earlier this month. The child, now 46 months old, was again started on antiretroviral therapy of zidovudine, lamivudine, and nevirapine. To date, she is tolerating the medication with no adverse effects, and treatment is decreasing virus levels, physicians said at a telephone conference organized by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Learning that the virus had rebounded after 27 months "felt like a punch to the gut," said Dr. Hanna Gay, MD, a pediatric HIV specialist at the University of Mississippi Medical Center in Jackson, who has been involved in the child's care since birth. "It's extremely disappointing. We had been hopeful that her remission would lead to bigger and better things."

That sentiment was echoed by NIAID Director Anthony S. Fauci, MD. "Certainly, this is a disappointing turn of events for this young child, the medical staff involved in the child's care, and the HIV/AIDS research community. Scientifically, this development 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 fact that this child was able to remain off antiretroviral treatment for 2 years and maintain quiescent virus for that length of time is unprecedented," said Deborah Persaud, MD, professor of infectious diseases at the John Hopkins Children's Center in Baltimore, Maryland, and one of the pediatric HIV experts involved in the ongoing analysis of the case. "Typically, when treatment is stopped, HIV levels rebound within weeks, not years."

The child was born prematurely in a Mississippi clinic in 2010 to an HIV-infected mother who did not receive antiretroviral medication during pregnancy and was not diagnosed with HIV infection until the time of delivery, an NIAID release stated. "Because of the high risk of HIV exposure, the infant was started at 30 hours of age on liquid, triple-drug antiretroviral treatment. Testing confirmed within several days that the baby had been infected with HIV. At 2 weeks of age, the baby was discharged from the hospital and continued on liquid antiretroviral therapy.

Unanswered Questions

"The baby continued on antiretroviral treatment until 18 months of age, when the child was lost to follow up and no longer received treatment," the statement said. "Yet, when the child was again seen by medical staff 5 months later, blood samples revealed undetectable HIV levels (less than 20 copies of HIV per milliliter of blood (copies/mL)) and no HIV-specific antibodies. The child continued to do well in the absence of antiretroviral medicines and was free of detectable HIV for more than 2 years."

At the clinical visit earlier this month, the child was found to have detectable HIV levels in the blood (16,750 copies/mL), said Dr. Gay. Repeat viral load blood testing performed 72 hours later confirmed this finding (10,564 copies/mL of virus). In addition, the child had decreased levels of CD4+ T-cells, a key component of a normal immune system, and the presence of HIV antibodies, which are signals of an actively replicating pool of virus in the body. On the basis of these results, the child was again started on antiretroviral therapy. Genetic sequencing of the virus indicated that the child's HIV infection was the same strain acquired from the mother.

Researchers need to study why there was a persistence of a reservoir of the virus in the absence of our ability to detect it, said Dr. Fauci. "How can someone be off therapy for 27 months and yet the virus remained suppressed? We don't know what triggered it." He said the child will continue to receive antiretroviral therapy indefinitely, possibly for life.

"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 harboring HIV infection," said Katherine Luzuriaga, MD, professor of molecular medicine, pediatrics, and medicine at the University of Massachusetts Medical School in Worcester.

"The case of the Mississippi child indicates that early antiretroviral treatment in this HIV-infected infant did not completely eliminate the reservoir of HIV-infected cells that was established upon infection but may have considerably limited its development and averted the need for antiretroviral medication over a considerable period," said Dr. Fauci. "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 even further."

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