The Mississippi baby? questions on a 'functional' cure

Author: Gillian Hunt, Nono Mkhize, Mark Cotton - 2013-04-10

A recent late breaker at CROI 2013 by D Persaud and colleagues documented a case where early ART may have prevented the establishment of a latent reservoir in an HIV-infected child and achieved a functional cure. A functional cure is different from a complete cure in that while the virus is not eliminated, it is kept under control in the absence of therapy and does not impact on patient well-being.

In this case, the mother was diagnosed with HIV in labour. At the time, her viral load was very low (2423 copies/ml) and CD4 count was high (644 cells/ml), suggesting a low viral inoculum to the baby. The child was initiated on an AZT/3TC/NVP (NVP at full dose, without the 2 week 'lead-in') regimen on second day of life following 2 separate positive HIV DNA and RNA tests (VL 19,812copies/ml). Three additional viral loads at day 7, 12 and 20 were positive. LPV/r was substituted for NVP from day 7 until discontinuation of therapy by the caregiver at 18 months. When the infant returned to care 8 months later, the HIV RNA was undetectable and remained so (<20 copies/ml) on 16 different measurements between 1 - 26 months despite discontinuation of treatment, and CD4% levels remained normal throughout. Using standard clinical assays, plasma viral load, PBMC DNA, and HIV-specific antibodies remained undetected following return to care. Using ultrasensitive methods, a single copy of HIV RNA was detected in plasma and 37 copies HIV DNA/million peripheral blood mononuclear cells (PBMC) were detected at age 24 months. At age 26 months HIV DNA was detected at 4 copies/million PBMC but with no 2-LTR circles. Follow-up of the child will continue to see if virus is once again detected in the child's blood.

Similar reports of functional cures have been reported following cessation of therapy in adults identified shortly after infection. Whilst these cases provide exciting insights into mechanisms of viral control, they remain isolated incidents and should not be regarded as the norm. At this stage, early initiation of ART should not be a reason to discontinue ART without expert consultation and outside of a structured trial. It is essential that pregnant women receive appropriate ART for pMTCT.

Further investigations and studies are critical to establish if aggressive and early treatment with ART may hold the key to functional cure (Saez-Cirion et al, PLoS Pathog 9(3): e1003211) and whether this can be translated into a treatment strategy. The case of the Mississippi baby, however, makes a compelling case for undertaking a diagnostic PCR in babies on day one of life or as soon as possible where pMTCT has been sub-optimal or non-existent, as in utero transmission (which is linked to rapid disease progression and death in young infants) is possible (Lillian et al, J Clin Microbiol 2012; 50: 2373-7). Here, early ART may be crucial.

Further information:

Later Breaker at CROI 2013 by D Persaud:

Further reading:

Similar reports in adults:

Authors: Dr Gillian Hunt and Dr Nono Mkhize, Centre for HIV and STI, NICD and Prof Mark Cotton, Department of Paediatrics and Child Health, Stellenbosch University.


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