04 March 2013
An infant apparently infected with HIV in utero or at birth appears to be the first case of “functional cure” in a baby, according US researchers presenting their findings at the 20th Conference on Retroviruses and Opportunistic Infections (CROI). The case is already spurring discussion of whether the baby had established infection, as did the “Berlin patient” cured of HIV infection after bone marrow transplantation from a donor with HIV-resistant cells.
Deborah Persaud, a highly regarded scientist at Johns Hopkins University in Baltimore, and colleagues from other sites tested blood and cell samples collected over the baby’s first 2 years of life. The mother delivered the child without knowing she had HIV infection. When HIV antibody and plasma HIV RNA tests established that the mother had HIV, testing began for the neonate.
Two separate samples collected on the infant's second day of life were positive in standard HIV DNA and HIV RNA assays. The virus genetically matched that of the mother, and plasma viral load stood at a relatively low 20,000 HIV RNA copies/mL. Triple antiretroviral therapy began 30 hours after birth. Viral load testing on days 7, 12, and 20 confirmed a detectable but steadily dropping plasma load, which became undetectable on day 29. Plasma viral load measured with a 20-copy assay remained undetectable through 26 months.
Antiretroviral therapy stopped at age 18 months, when the child's mother stopped returning for care, and the child has taken no antiretrovirals though age 2.5 years. Ultrasensitive assays deployed by Persaud and colleagues detected a solitary copy of HIV RNA at age 24 months and 37 copies of HIV DNA per million peripheral blood mononuclear cells (PBMCs) enriched for monocytes. No evidence of replication-competent HIV could be detected after coculture of 22 million purified resting CD4 cells.
Samples collected when the child was 26 months old showed 4 HIV DNA copies per million PBMCs but no 2-LTR circles. HIV 2-LTR circles indicate that HIV genetic material is making its way into the nucleus of an infected cell.
Persaud and colleagues believe “this is the first well-documented case of functional cure in an HIV-positive child.” The case, they propose, “suggests that very early ART may prevent establishment of a latent reservoir and achieve cure in children.”
How to consider the merits of this functional cure claim revolve around the latent HIV reservoir. Adults with HIV (such as the cured Berlin patient) have such a reservoir, which prevents discontinuous antiretroviral therapy from halting viral replication. Persaud and coworkers believe prompt triple-antiretroviral therapy blocked establishment of a latent viral reservoir in this infant.
D. Persaud, H. Gay, C. Ziemniak, et al. Functional HIV cure after very early ART of an infected infant. 20th Conference on Retroviruses and Opportunistic Infections. 3-6 March 2013. Atlanta. Abstract 48LB.
A. Pollack, D.G. McNeil Jr. In medical first, a baby with H.I.V. is deemed cured. New York Times. 4 March 2013.
For the CROI site
For the New York Times article