Functional HIV Cure after Very Early ART of an Infected Infant
Deborah Persaud*1, H Gay2, C Ziemniak1, YH Chen1, M Piatak3, T-W Chun4, M Strain5, D Richman5, and K Luzuriaga6
1Johns Hopkins Univ Sch of Med, Baltimore, MD, US; 2Univ of Mississippi Med Ctr, Jackson, US; 3Frederick Natl Lab for Cancer Res, MD,US; 4NIAID, NIH, Bethesda, MD, US; 5Univ of California San Diego, La Jolla and VA San Diego Hlthcare System, US; and 6Univ of Massachusetts Med Sch, Worcester, US
Background: A single case of HIV cure occurred in an infected adult with a bone marrow transplant. We report a case of functional HIV cure in a 26-month-old infected child who initiated ART at 30 hours of age.
Methods: Infant exposure to HIV was confirmed through review of maternal HIV antibody and plasma viral load tests, including HIV drug resistance testing. Infant infection was documented using standard HIV DNA polymerase chain reaction (PCR) and plasma viral load. ART administration was confirmed with medical and pharmacy records and maternal report of medication adherence. Persistence of HIV infection following treatment discontinuation was assessed using standard clinical assays that included plasma viral load, proviral DNA, and HIV antibody testing. Ultrasensitive HIV DNA (droplet digital PCR), plasma viral load (single copy) assays, and quantitative co-culture assays were done at age 24 and 26 months to further assess HIV persistence. HLA typing was done to confirm matching of the mother–infant pair.
Results: Maternal infection with wild type subtype B HIV was verified. The mother and infant shared HLA haplotypes. Infant infection was confirmed by positive HIV DNA and RNA testing on 2 separate blood samples obtained on the 2nd day of life. 3 additional plasma viral load tests (days of life 7, 12, and 20) were positive before reaching undetectable levels at age 29 days. Plasma HIV RNA remained undetectable (<20 copies/mL) on 16 different measurements obtained between 1 through 26 months of age despite ART discontinuation at age 18 months. Using ultrasensitive methods, a single copy of HIV RNA was detected in plasma at age 24 months and 37 copies HIV DNA/million peripheral blood mononuclear cells (PBMC) enriched for monocytes were detected. Replication-competent virus was not detected following co-culture of 22 million purified resting CD4+ T cells. At age 26 months HIV DNA was detected at 4 copies/million PBMC but with no 2-LTR circles. Plasma viral load, PBMC DNA, and HIV-specific antibodies remained undetectable with standard clinical assays, confirming a state of functional HIV cure.
Conclusions: This is the first well-documented case of functional cure in an HIV+ child and suggests that very early ART may prevent establishment of a latent reservoir and achieve cure in children.