The 4-year-old Mississippi child whose HIV infection was put in remission with pre-emptive anti-viral treatment shortly after birth has shown signs of viral recurrence, according to the team that has been following the patient since birth. That team includes Deborah Persaud, M.D., a pediatric HIV specialist at the Johns Hopkins Children’s Center, who performed the initial and all subsequent virological analyses on the case; Hannah Gay, M.D., a pediatrician at the University of Mississippi Medical Center who has been treating and following the child since birth; and immunologist Katherine Luzuriaga, M.D., of the University of Massachusetts Medical School, who conducted immunological monitoring of the child.
In light of the new findings, the child has started anti-retroviral therapy, is doing well and has had excellent response to the treatment. The child remains under the medical care of Gay at the University of Mississippi Medical Center.
Persaud and colleagues described the latest development as decidedly disappointing, but they say the case remains a medical first and a significant milestone in pediatric HIV research.
“This is a definite setback on our quest to eradicate HIV, but we are not discouraged,” Persaud says. “This latest development highlights how much more we still have to learn about HIV and its hideouts. Nonetheless, achieving full remission for more than two years in the absence of treatment represents an important medical advance that has given us critical insights and illuminated important new questions.”
Described as the first documented instance of HIV remission in a child, the Mississippi case invigorated the field of HIV research by suggesting that very early treatment with anti-retroviral drugs may help quash the formation of viral reservoirs — HIV hideouts that remain unreachable for antiviral drugs and preclude HIV clearance in the majority of patients. Typically, HIV infection is reignited full blast within mere weeks of stopping treatment. By contrast, the Mississippi child remained free of active infection, with undetectable viral loads and free of HIV antibodies for more than two years.
A detailed report of the case was published in the Nov. 7, 2013 issue of The New England Journal of Medicine.
The child was born to an HIV-infected mother who did not receive anti-viral treatment during pregnancy and was not diagnosed with HIV until the time of delivery. The baby tested positive for HIV at birth, and pediatricians at the University of Mississippi Medical Center initiated treatment with full-dose anti-retroviral drugs 30 hours after delivery. A series of tests in the subsequent days and weeks showed progressively diminishing viral presence in the infant’s blood, until it reached undetectable levels 29 days after birth. The infant remained on antivirals until 18 months of age, at which point the child was lost to follow-up for a while and, physicians say, stopped treatment. Upon return to care, about five months after treatment stopped, the child underwent repeated standard HIV tests, none of which detected virus in the blood. Ultrasensitive tests designed to sniff out trace amounts of HIV repeatedly showed lack of replicating virus.
Persaud and colleagues remained cautiously optimistic and continued to vigilantly monitor the infant every one to two months. In total, the child remained free of active virus and was considered in remission for 27 months until early July when a blood sample obtained during a routine clinical visit detected HIV levels in the blood. Repeat viral load blood testing performed 72 hours later confirmed the initial findings. The child also had a drop in the levels of CD4+ cells — HIV’s favorite target — as well as presence of HIV antibodies, which previously had remained undetectable. Based on these test results, the physicians initiated prompt treatment with anti-viral drugs. The viral loads have decreased and CD4 cells rebounded as a result, the team says.
Researchers say their next step is to determine whether the remission can be prolonged even further and to pinpoint the exact mechanism that enabled the child to remain off treatment for more than two years without detectable virus and without measurable immunologic response.
“The case remains important because it shows that while anti-retroviral treatment may not prevent reservoir formation altogether, it does appear to significantly slow and limit the emergence of these treatment-defying viral hideouts to a point where a patient may be able to forego antivirals for years,” Persaud says.
The Johns Hopkins University