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HIV found in Mississippi Baby, disappointing hopes for cure

, by Liz Highleyman

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Deborah Persaud from 2013 Retrovirus Conference (photo: Liz Highleyman)

A Mississippi child who maintained undetectable HIV for more than two years off antiretroviral therapy (ART) has been found to still be infected, tempering optimism about a functional cure in the lead-up to the 20th International AIDS Conference next week in Melbourne.

The Mississippi Baby grabbed headlines at the 2013 Retrovirus Conference, where researcher Deborah Persaud of Johns Hopkins Children’s Center first described the case. Further details were published in the November 7, 2013, New England Journal of Medicine.

The girl was born in 2010 to an HIV-positive mother who did not receive prenatal care and was not diagnosed until the time of delivery. The baby was delivered prematurely, before the woman could be given drugs to prevent mother-to-child transmission, and the infant was started on a full combination antiretroviral (ART) regimen 30 hours after birth. (Usually babies only get a single drug as extra protection if the mother gets antiretrovirals during delivery.)

The baby continued on combination treatment for a year with good viral suppression. She then began missing clinic visits and was taken off treatment by her caretakers. When the girl was brought back for care at age 2, however, her viral load was still undetectable despite being off ART for several months.

At this year’s Retrovirus Conference, Persaud reported that repeated, extensive testing — including tests for HIV DNA or genetic material in peripheral blood cells — still did not find replication-competent virus after two years without treatment.

But as researchers reported in a National Institute of Allergy and Infectious Diseases press releaseand media briefing on July 10, during a routine clinical visit earlier this month the girl was found to have detectable HIV, with a viral load of 16,750 copies. She also had a decreasing CD4 T-cell count, indicating that the virus was killing off immune cells. She was put back on ART and was said to be tolerating treatment well and showing reduced viral load as the drugs start to work.

The latest findings represent a setback for HIV cure research, but even negative findings provide more clues about where HIV hides in the body and how it might be attacked.

“The fact that this child was able to remain off antiretroviral treatment for two years and maintain quiescent virus for that length of time is unprecedented,” said Persaud. “Typically, when treatment is stopped, HIV levels rebound within weeks, not years.”

HIV establishes reservoirs of latent viral genetic material in resting T-cells soon after infection, where it is not susceptible to natural immune responses or antiretroviral drugs. When these resting cells are later activated, this viral blueprint can “wake up” and start producing new virus. Researchers have been exploring several approaches, including very early ART to prevent establishment of reservoirs.

The NIH-funded IMPAACT (International Maternal, Pediatric, Adolescent AIDS Clinical Trials Network) has been planning a trial of at-risk infants started on intensive combination therapy immediately after birth. If HIV remained undetectable after two or more years, they would undergo experimental treatment interruption.

After the latest findings, however, this approach appears more ethically questionable. Researchers first want to learn more about what enabled the Mississippi child to stay off treatment so long without viral rebound or any apparent negative health effects.

“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,” said NIAID director Anthony Fauci. “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.”

Liz Highleyman (liz (at) hivandhepatitis.com) is a freelance medical writer and editor-in-chief of HIVandHepatitis.com.

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