Steps Towards HIV Cure
"Baby Steps on the Road of HIV Eradication" is the nice title given to an editorial by Scott M. Hammer published in the New England Journal of Medicine on October 23, 2013. This editorial comes with a brief report from Deborah Persaud intitled "Absence of Detectable HIV-1 Viremia after Treatment Cessation in an Infant", the story of the famous "Mississippi child" with all the details...
The story of the "Mississippi child" was first presented last March at CROI.
The infant was born by spontaneous vaginal delivery at 35 weeks of gestation to a HIV-positive woman who had received no prenatal care. Delivery occured before antiretroviral prophylaxis was administered.
The detection of HIV DNA in PBMC from infant blood obtained at 31 hours of age and the presence of HIV-1 viremia (19,812 copies of HIV RNA/ml) in a separate sample collected at 31 hours of age, met the standard diagnosis criteria for HIV infection in the infant.
The mother viral load at 24 hours post delivery was 2423 copies/ml.
ART was initiated in the infant (AZT, 3TC, NVP) at 30 hours of age and NVP was switched to LPV/r at 1 week of age to avoid resistance selection.
With these regimens, plasma viral load decrease in the infant following a 2 phase decay and reached undetectable levels at 29 days of age.
The infant was not breast-fed.
Between 18 and 23 months of age, the child missed several clinic visits.
In blood samples obtained at 23 and 24 months of age, plasma viremia was undetectable, as was an HIV antibody test.
When the child was brought to care at 23 months of age, the mother admitted that she had stopped ART when the child was 18 months of age.
At the time of the N Engl J Med report, the child has not received any antiretroviral drugs through 30 months of age.
Neither the mother nor the infant had HLA class I alleles that are associated with spontaneous control of HIV infection; both were nonmutated for CCR5.
Viral RNA was detected at a single-copy level in plasma obtained at 24 months of age but not at 26 months of age.
HIV-1 proviral DNA was detected near the limits of detection at both time points.
However, a culture of 22 million resting CD4+ T cells obtained at 24 months of age did not yield replication-competent HIV.
No HIV specific immune responses could be detected.
Despite traces of HIV-1 nucleic acid (that might represent defective virus or false positive signals), the authors conclude that very early ART in this case interfered with the establishment of persistent replication-competent HIV-1 reservoirs.
At least 18 months after ART cessation, this child has not experienced any rebound in plasma HIV viremia.
1-Hammer SC. Baby Steps on the Road to HIV Eradication. N Engl J Med 2013 Published ahead of print
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 Published ahead of print. DOI: 10.1056/NEjMoa1302976
Key words: HIV cure, HIV eradication, HIV persistence, HIV reservoirs, Mississippi child