Back HIV Treatment Search for a Cure Second Potentially Cured Baby Has HIV Relapse Soon After Stopping Treatment

Second Potentially Cured Baby Has HIV Relapse Soon After Stopping Treatment

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An Italian child who started antiretroviral treatment soon after birth and had undetectable plasma viral load, no apparent HIV DNA, and tested HIV antibody negative nevertheless experienced viral rebound shortly after a treatment interruption, once again disappointing hopes for a cure, researchers reported in the October 4 edition of The Lancet.

In recent years a number of cases of HIV "functional cures" have been reported in which individuals have been able to control HIV for prolonged periods while off antiretroviral therapy (ART).

As first reported at the 2013 Retrovirus Conference, one especially promising case involved a baby in Mississippi born to an HIV positive mother who did not receive antiretrovirals to prevent mother-to-child transmission. Considered at high risk for infection, the baby was started on combination ART within about 30 hours after birth.

After remaining on ART with full viral suppression for a year and a half, the child was lost to follow-up and stopped treatment. When the girl was brought back for care at about 2 years old, however, her viral load was undetectable despite being off ART for several months. Extensive testing over the next year failed to detect replication-competent virus. But asreported this summer, during a routine clinical visit the girl (now nearly 4 years old) was found to have detectable HIV in her blood and a falling CD4 T-cell count, and again started ART.

Vania Giacomet, Mario Clerici, and colleagues from the University of Milan have now described another baby who was treated early, stopped ART -- this time intentionally -- and soon experienced viral rebound.

In this case, a woman came to Luigi Sacco Hospital while in labor in December 2009. She was unaware of her HIV status, had not received antiretrovirals to prevent mother-to-child transmission, and was found to have a high viral load. She gave birth to a baby boy who tested positive for HIV antibodies, p24 antigen, and plasma HIV RNA.

This infant was started on intensive combination ART within 12 hours after birth -- even sooner than the Mississippi baby. Extensive testing was performed over the next 3 years, showing that the child had undetectable plasma viral load, no detectable HIV genetic material in peripheral blood cells, and he no longer tested HIV antibody positive.

Given the promising findings regarding the Mississippi baby -- who had not yet relapsed -- the Italian child's doctors and mother decided to attempt an experimental treatment interruption to see if he might be cured. Unfortunately, however, the child was found to have detectable viral load 2 weeks after stopping ART, reaching nearly 37,000 copies/mL. Treatment was resumed and the boy again achieved undetectable plasma viral load, but other tests had turned positive.

The return of HIV in the Italian child, the Mississippi baby, and a small number of bone marrow transplant recipients in Boston and in Australia indicate that despite maintaining undetectable HIV RNA and DNA for years, viral reservoirs were not completely eliminated, setting the stage for recurring viral replication when ART was withdrawn. This leaves Berlin Patient Timothy Brown, who received bone marrow transplants from a donor with an uncommon mutation (CCR5-delta-32) that protects T-cells from viral entry, as the only person who still appears to be cured of HIV, now 7 years after stopping ART.

One difference in the Italian case, according to a press release issued by The Lancet, is that child’s immune system continued to show signs of responding to HIV even after the virus became undetectable, which was not true for the Mississippi baby or Brown. 

"The availability of many classes of potent antiretroviral drugs has substantially decreased HIV morbidity and mortality, but these drugs cannot eradicate the virus because they do not eliminate viral reservoirs," the Italian study authors concluded. "The search for an HIV cure continues."

10/8/14

Reference

V Giacomet, D Trabattoni, N Zanchetta, et al. No cure of HIV infection in a child despite early treatment and apparent viral clearance. The Lancet 384(9950):1320. October 4, 2014.

Other Source

The Lancet. Second Case of Apparent HIV "Cure" in a Baby Followed by Reappearance of Virus. Press release. October 2, 2014.