Still No Detectable HIV RNA or DNA in "Mississippi Baby" at 30 Months

HIV RNA in blood and proviral DNA in peripheral blood mononuclear cells (PBMCs) remain undetectable through 30 months of age in the Mississippi baby treated for HIV with triple therapy 30 hours after birth, but not treated between 18 and 23 months of age because of missed clinic visits and failure to refill prescriptions. Evidence to date, reported in the New England Journal of Medicine, suggests that immediate antiretroviral therapy protected the child from established HIV infection.

This noted case, first reported in March 2013, involves an infant in whom zidovudine, lamivudine, and nevirapine were begun early in the second day of life because of likely exposure to HIV from a seropositive mother. HIV DNA could be detected in PBMCs 30 hours after birth, and HIV RNA could be detected in plasma 31 hours after birth. HIV RNA remained detectable (but falling) at age 6 days, 11 days, and 19 days before becoming undetectable.

Treatment continued until the child was 18 months of age—or perhaps 15 months, according to pharmacy records—then stopped when the mother and child stopped keeping clinic visits.

The mother and child returned to care when the child was 23 months old, and at that point no HIV RNA could be detected in blood. Another HIV RNA test at 24 months and an HIV DNA assay at 24 months were negative. An HIV antibody test in the child was also negative.

Routine clinical assays could not detect HIV in the child through 30 months of age, the time of this report. The child was HIV antibody-negative at 24, 26, and 28 months. A culture of 22 million resting CD4 cells at 24 months of age did not yield replication-competent HIV.

The researchers do not use the word "cure" to describe this case. They write that "the absence of rebound viremia, the undetectable replication-competent virus, the almost-complete disappearance of cell-associated HIV-1 DNA, and the absence of HIV-1-specific immune responses while the child was not receiving antiretroviral therapy suggest that replication-competent HIV-1 reservoirs may not have been established or were markedly abated, if not extinguished."

In an accompanying editorial, Columbia University's Scott Hammer warns that this case "may be unique, and thus we have to exercise caution before inferring general principles from this case report." But he adds that "individual case reports can provide proofs of principle, stimulate hypotheses, and lead to carefully designed experimental therapeutic studies involving both adults and children that, we hope, will lead us down the road to the reduction or eradication of the HIV-1 reservoir."

Sources:

Deborah Persaud, Hannah Gay, Carrie Ziemniak, Ya Hui Chen, Michael Piatak, Tae-Wook Chun, Matthew Strain, Douglas Richman, Katherine Luzuriaga. Absence of detectable HIV-1 viremia after treatment cessation in an infant. New England Journal of Medicine. Published online 23 October 2013. DOI: 10.1056/NEJMoa1302976.

Hammer SM. Baby steps on the road to HIV eradication. New England Journal of Medicine. Published online 23 October 2013.

Written by Mark Mascolini on behalf of the International AIDS Society