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Second Swiftly Treated Baby Seems to Have Cleared HIV
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CROI 2014, March 3-6, 2014, Boston
Mark Mascolini
Another US baby treated with combined antiretrovirals soon after birth appeared to clear HIV from resting T cells and to be free of HIV 9 months after birth [1]. Unlike the so-called Mississippi baby, reported in 2013 [2], this baby girl in Long Beach, California, continues her antiretroviral regimen. But sensitive assays can detect no HIV DNA in peripheral blood mononuclear cells (PBMCs) or resting CD4 cells.
In both cases, clinicians began antiretroviral therapy in the first days of life, shortly after confirming HIV infection in the baby. The Mississippi baby, now 41 months old with no detectable HIV, stopped receiving treatment when her mother dropped out of care for several months. When the baby returned--untreated for months--no HIV could be found in blood [2]. This infant has not received antiretrovirals for 23 months. "Trace" amounts of HIV DNA remain detectable in PBMCs, but replication-competent virus and HIV-specific immune responses cannot be detected.
Long Beach clinicians confirmed that a newborn girl had HIV RNA in blood and cerebrospinal fluid and HIV DNA in cells 4 hours after birth. Knowing about the Mississippi baby, the Long Beach group began treatment immediately with zidovudine, lamivudine, and nevirapine. At 2 weeks they switched nevirapine to lopinavir/ritonavir, and therapy has continued for 9 months. The mother took no antiretrovirals during pregnancy and had a viral load of 138,811 copies near delivery.
HIV RNA has remained undetectable in blood with a 20-copy assay for 9 months. A clinical assay for proviral DNA came back negative 6 days after treatment began and remained negative at 1.6 months and 2.2 months. Infectious virus could not be recovered from the baby at 1, 3, or 9 months. Six days after treatment began, proviral DNA lay below 5.3 copies per million PBMCs, the assay limit. Western blot determined the infant's serostatus as indeterminate at 3 months and negative at 9 months. The child has a normal CD4 percent. (Routine clinical assays were done at Long Beach; latency studies and all specialized tests were done in the Johns Hopkins laboratory of Deborah Persaud.)
Persaud, the principal investigator in both cases, did not use the word "cure" to describe either child, preferring the terms "seroreversion" and "viral remission." She concluded that the findings support "restriction of HIV spread with very early cART."
Persaud and colleagues proposed that their findings "emphasize the need for standardized approaches and development of sensitive laboratory markers to guide optimal management of very early treated HIV-1 infected infants toward viral remission."
A trial of antiretroviral therapy for infants with confirmed HIV infection in the first 48 hours of life will begin soon. Confirmation of the Mississippi and Long Beach cases could create a strong impetus to test HIV-exposed infants immediately after birth and start antiretrovirals in those who test positive.
References
1. Persaud D, Deveikis A, Gay H, et al. Very early combination antiretroviral therapy in perinatal HIV infection: two case studies. CROI 2014. Conference on Retroviruses and Opportunistic Infections. March 3-6, 2014. Boston. Abstract 75LB.
2. Persaud D, Gay H, Ziemniak C, et al. Absence of detectable HIV-1 viremia after treatment cessation in an infant. N Engl J Med. 2013;369:1828-1835. http://www.nejm.org/doi/full/10.1056/NEJMoa1302976
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