Early application of antiretroviral therapy may prevent establishment of a latent reservoir and achieve cure in HIV-positive children, according to results of a case report presented at the 2013 Annual CROI Meeting in Atlanta.
Researchers from Johns Hopkins Children’s Center, the University of Mississippi Medical Center and the University of Massachusetts Medical School presented a novel case of a “functional HIV cure” in a 26-month-old infected child who commenced ART at 30 hours of age.
“Prompt antiviral therapy in newborns that begins within days of exposure may help infants clear the virus and achieve long-term remission without lifelong treatment by preventing such viral hideouts from forming in the first place,” Deborah Persaud, MD, a Johns Hopkins Children’s Center virologist, said in a press release.
The researchers confirmed infant exposure to HIV through review of maternal HIV antibody and plasma viral load tests, together with HIV drug resistance testing. Infant infection was identified using standard HIV DNA polymerase chain reaction and plasma viral load.
The researchers established ART administration with medical and pharmacy records and maternal report of medication adherence. In addition, the researchers evaluated persistence of HIV infection after treatment termination using standard clinical assays that included plasma viral load, proviral DNA and HIV antibody testing.
Ultrasensitive HIV DNA, plasma viral load assays and quantitative co-culture assays were performed at 24 and 26 months to further review HIV persistence.
The researchers verified maternal infection with wild-type subtype B HIV, and both mother and infant shared human leukocyte antigen (HLA) haplotypes. Infant infection was confirmed by positive HIV DNA and RNA testing on two separate blood samples obtained on the second day of life.
Three additional plasma viral load tests — obtained on days 7, 12 and 20 — were positive before reaching undetectable levels at age 29 days.
According to researchers, plasma HIV RNA remained undetectable (<20 copies/mL) on 16 different measurements obtained from 1 to 26 months of age, despite ART discontinuation at age 18 months.
The researchers observed replication-competent virus after co-culture of 22 million purified resting CD4+ T cells. At age 26 months, HIV DNA was detected at 4 copies/million peripheral blood mononuclear cells (PBMC) but with no 2-long terminal repeat (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.
“Complete viral eradication on a large scale is our long-term goal but, for now, remains out of reach, and our best chance may come from aggressive, timely and precisely targeted use of antiviral therapies in high-risk newborns as a way to achieve functional cure,” Katherine Luzuriaga, MD, immunologist and professor at the University of Massachusetts Medical School, said in a press release.
For more information:
Persaud D. Abstract #48LB. Presented at: 2013 Annual CROI Meeting; March 3-6, 2013; Atlanta.