Functional HIV Cure in an Infant
The first case of HIV cure in an infant from an infected mother not aware of her status was reported by Deborah Persaud (John Hopkins University School of Medicine, Baltimore, USA) at the 2013 CROI held in Atlanta.
Besides the great interest of the case report, this presentation underlines the difficulties of defining what cure is, as well as the limits of current biological assays to assess the persistence of HIV in an individual.
This child was born at 35 weeks of gestation via normal spontaneous vaginal delivery. A rapid HIV test was done to the mother which was positive.
No antiretroviral was administered to the mother during delivery. Blood tests subsequently showed that the mother was infected by a sub-type B strain, had 644 CD4+ T cells/mm3 and a viral load of 2423 copies/ml.
Two blood samples were taken from the infant, respectively at 30 and 31 hours of life. These samples were positive for HIV DNA and RNA (19812 copies/ml).
Antiretroviral therapy was started orally in the infant at 31 hours of age with AZT/3TC/NVP (nevirapine BID at therapeutic doses). At 1 week, NVP was switched to Kaletra* and this combination was continued until 18 months of life, when the infant was lost to follow-up.
The infant was seen again at 23 months of age. Antiretroviral therapy had, in fact, been stopped at 18 months. despite this, no viremia was detected, no HIV DNA and the HIV ELISA test was negative.
Using ultrasensitive assays:
-no reactive band on Western blot was found at the ages of 2 and 2.2 years;
-no HIV specific CD8 or CD4 T cell responses were detected;
-low level HIV DNA was detected using the droplet PCR approach,
-viremia was found one time at the limit of detection of 1 copy of HIV RNA/ml
-no infectious virus could be recovered from the culture of 22 x 106 cells.
Furthermore, no deletion was found on the CCR5 gene.
The child is now 2.5 years old.
These data suggest that very early ART in infants may prevent the establishment of the latent HIV reservoir, may be in part because at the time of birth there are no memory T cells yet.
Key words: HIV cure, HIV eradication, HIV reservoirs, curative HIV therapeutic strategies