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"Functional Cure" of HIV Claimed for Baby Treated 30 Hours After Birth
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20th Conference on Retroviruses and Opportunistic Infections, March 3-6, 2013, Atlanta
Mark Mascolini
An HIV-infected US infant treated from 31 hour after birth had no detectable viral load, no detectable HIV DNA in blood cells, and no HIV-specific antibodies at 26 months of age on standard tests, even though antiretroviral therapy (ART) stopped at age 18 months [1]. Deborah Persaud (Johns Hopkins University) and colleagues believe their findings confirm "a state of functional HIV cure."
Speedy treatment after birth appeared to work like postexposure prophylaxis (PEP), stopping HIV from getting a foothold in this baby's body and establishing a latent viral reservoir. Evidence that the baby was infected persisted, however, in vanishingly small levels of HIV RNA and HIV DNA detectable in blood and cells. But the researchers do not believe these viral traces can reestablish active infection.
US HIV experts including Daniel Kuritzkes (Harvard) and Steven Deeks (University of California, San Francisco) are reserving judgment on whether the child had established HIV infection, the New York Times reports [2]. "The one uncertainty is really definitive evidence that the child was indeed infected," Kuritzkes told the Times.
Persaud and colleagues believe their findings show the infant did have HIV infection--though perhaps not an established latent reservoir. "For pediatrics, this is our Timothy Brown," Persaud told the Times, referring to the "Berlin patient" cured of HIV after bone marrow transplantation from a donor with cells resistant to HIV.
The researchers confirmed exposure to HIV by checking maternal HIV antibody and plasma HIV RNA tests, including HIV resistance testing. The baby appeared to be infected with wild-type (nonmutant) HIV-1 subtype B. Persaud and coworkers believe they documented HIV infection in the infant through standard HIV DNA polymerase chain reaction and plasma HIV RNA testing. Positive HIV DNA and HIV RNA testing on separate infant blood samples collected on the second day of life showed that the child carried HIV that was genetically matched to the mother's virus. Plasma viral load at that point was around 20,000 copies [2], relatively low for an infant.
Three-drug treatment of the Mississippi infant began within 31 hours of birth and continued to the age of 18 months. Plasma HIV RNA tests remained positive on days 7, 12, and 20, then became undetectable at age 29 days. From 1 through 26 months, plasma HIV RNA remained below the detection limit of a 20-copy assay repeated 16 times.
Antiretroviral therapy stopped at age 18 months when the mother and child dropped out of care. After the child returned to care, ultrasensitive assays detected a single copy of HIV RNA at age 24 months and 37 copies of HIV DNA per million peripheral blood mononuclear cells (PBMCs) enriched for monocytes. Samples yielded no evidence of replication-competent HIV after coculture of 22 million purified resting CD4 cells.
When the infant was 26 months old, an ultrasensitive assay spotted 4 HIV DNA copies per million PBMCs but no 2-LTR circles (which indicate that HIV genetic material is being imported into the nucleus of an infected cell). Standard clinical assays remain negative for HIV RNA, PBMC HIV DNA, and HIV-specific antibodies.
"This is the first well-documented case of functional cure in an HIV-positive child," Persaud and colleagues maintain. The case, they believe, "suggests that very early ART may prevent establishment of a latent reservoir and achieve cure in children."
The child is now 2.5 years old and has not taken antiretrovirals for a year.
References
1. Persaud D, Gay H, Ziemniak C, et al. Functional HIV cure after very early ART of an infected infant. 20th Conference on Retroviruses and Opportunistic Infections. March 3-6, 2013. Atlanta. Abstract 48LB.
2. Pollack A, McNeil DG Jr. In medical first, a baby with H.I.V. is deemed cured. New York Times. March 4, 2013.
http://www.nytimes.com/2013/03/04/health/for-first-time-baby-cured-of-hiv-doctors-say.html.
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