March 5, 2014
The "Mississippi Child" remains in HIV remission and another child may also be functionally cured of HIV after very early treatment, according to a study presented by Deborah Persaud, M.D., at CROI 2014 in Boston.
To recap, the case of the cured "Mississippi Child" (formerly the "Mississippi Baby") was first presented at last year's CROI, detailing an HIV-positive newborn who was started on treatment within 31 hours of age, and showed no signs of HIV after her mother discontinued her treatment at 18 months.
According to Persaud, the Mississippi Child is now 41 months old and still functionally cured after being off treatment for 23 months. Persaud also presented findings on a second child, a 9-month-old, who was born with HIV, but treated within four hours of birth.
The tests that the researchers used to diagnose and monitor the children included HIV DNA and RNA tests, CD4 and CD8 T-cell percentages by flow cytometry, as well as HIV antibody tests with ELISA followed by Western blot confirmation. Using these tests, the two children were both confirmed positive at birth and subsequently started on treatment.
To monitor any HIV persistence in the children, the researchers used ultrasensitive tests to assess proviral DNA, residual viremia (testing for 1 or less than 2 copies/mL), replication-competent HIV reservoirs, non-induced proviral genomes, full-length HIV sequencing and maternal microchimerism.
The researchers also tested to see if the children were elite controllers, but found no evidence of mutations that would confer virologic control in the absence of treatment.
For the Mississippi Child, viral load tests with a limit of 20 copies/mL continued to show sustained HIV remission up to 23 months after treatment interruption. Testing for residual viremia using HIV RNA assays sensitive to less than 1 copy/mL, the researchers continued to find no HIV up to 22 months after treatment interruption. Furthermore, they were unable to detect any replication-competent resting CD4 cell latent reservoir virus up to 18 months after treatment interruption.
However, when testing for proviral DNA, the researchers continued to detect HIV DNA near the lower limits of detection, which further investigation at 40 months of age showed was not a result of maternal microchimerism. Although the researchers are unsure of the clinical relevance of the persistent detection of proviral DNA, it does not signify impending viral rebound, Persaud said.
Overall, the Mississippi Child is still considered to be in remission, with no detectable viral load or HIV reservoir using the most sensitive tests available, supporting the researchers' hypothesis that very early treatment forms a barrier to the formation of HIV reservoirs in perinatal infection.
The second child was confirmed positive using an HIV DNA test at 4 hours of age, with HIV RNA tests showing a viral load of 217 copies/mL at 36 hours of age and 32 copies/mL at 6 days of age. The infant was started on zidovudine/lamivudine (Combivir) and nevirapine (Viramune) at 4 hours of age, with the addition of lopinavir/ritonavir (Kaletra) from 2 weeks to 3.4 months of age.
By 11 days of age, the infant's viral load had become undetectable using a viral load test capable of detecting values as low as 20 copies/mL. At 9.5 months of age, the infant was still on treatment and continued to have an undetectable viral load. The infant tested negative using an HIV DNA test at 2.2 months of age, and tested negative using a Western blot test at 9 months of age. However, like the Mississippi Child, there is persistent detection of proviral DNA at very low levels.
While the two cases show the benefits of very early treatment, they also highlight the challenges of monitoring and managing early-treated infants toward HIV remission, Persaud said. When asked about the clinical implications of the study, Persaud expressed hope that the findings could lead to a better strategy in treating and potentially curing HIV-positive newborns.
Warren Tong is the research editor for TheBody.com and TheBodyPRO.com.
Follow Warren on Twitter: @WarrenAtTheBody.