Baby Cure Study
The ‘Mississippi baby’ received ART at 30hrs of age, and appeared to be cured following ART discontinuation. However, viral load subsequently rebounded. Anecdotal cases such as this child, and the ‘Visconti child’, presented very recently at IAS 2015 in Vancouver, have generated considerable interest in the possibility that children might be different from adults in terms of cure potential. Following viral rebound in the case of the Mississippi child, and other reports describing rebound in similar cases, the idea that early ART alone might suffice has been discarded.
However, several studies demonstrate that early ART initiation reduces the size of the latent viral reservoir, in both children and adults. We propose that there is substantially greater potential to cure HIV in children for the following reasons:
- The feasibility to initiate ART within hours of birth following in utero infection;
- (The impact of immune ontogeny: a) on the ability of HIV to establish a long-lived viral reservoir (CD4 T cells in the blood are phenotypically naïve and express no CCR5 at birth); b) on the nature of the virus; and c) on the immune response;
- Greater thymic activity in childhood, which substantially affects the contribution the immune response could play in eliminating HIV latency.
Additional factors unique to in utero paediatric infection may play a role in achieving long term remission off antiretroviral therapy or a true cure for HIV infection through an enhanced HIV-specific immune response, including
- Pre-adaptation of the transmitted virus to the inherited maternal HLA alleles;
- Enrichment in infected children of HLA molecules associated with high viral loads in adult infection;
- Adaptation of virus successfully transmitted across the placenta.
We recently have initiated a study in KwaZulu-Natal, South Africa, designed initially to identify in utero HIV-infected infants at birth, and initiate ART within 24-48hrs of birth. The longer-term goals of these studies is to identify children entered onto this study who, after a period on ART have undetectable viral reservoirs and undetectable HIV-specific immunity. These subjects would then be eligible for enrolment into Phase I trials designed to test new approaches to eradicate the viral reservoirs altogether prior to ART discontinuation.
Highly effective prevention of mother-to-child transmission (MTCT) programmes have now reduced MTCT to ~1.5% in South Africa. However there are 0.3m children born to HIV+ve women each year in South Africa. These initial studies therefore are highly challenging, but the two study sites in KwaZulu-Natal we have identified, at Stanger and Edendale Hospitals, have >1600 births/year, of which >6000 are to HIV-infected women (maternal seroprevalence 39%). We estimate identifying and initiating ART within 24-48hrs of birth 25-50 in utero infected children per year. In the first 45 days of the study at Stanger we have identified 4 in utero infected babies and initiated ART at between 4hrs and 24hrs of age in each of these. The study is projected to start at Edendale Hospital on 1st October 2015.
Philip Goulder (Oxford), Thumbi Ndung’u (KwaZulu-Natal), Sharon Lewin (Melbourne)
Project Manager: Ken Sprenger
Paediatricians: Yeney Graza (Stanger), Jeroen van Lobenstein (Stanger), Kevin Spicer (Edendale), Malini Krishna (Edendale), Roopesh Bhoola (Edendale)
Clinical Coordinator: Pat Mbatha
Sister/Counsellors: Gugulethu Mthiyane (Stanger), Sizakele Zondi (Stanger), Nozipho Phetha (Edendale/Imbalenhle), Daphne Xulu (Edendale/Imbalenhle)
Nurse: Royal Masuku (Ithembalabanthu)
Counsellor: Nicky Linda (Ithembalabathu)
Supervisors: Al Leslie (KRITH), Thumbi Ndung’u (DDMRI/KRITH), Sharon Lewin (Melbourne)
Post-docs: Max Muenchhoff (KRITH), Julia Roider (KRITH), Emily Adland (Oxford)
Research Assistants: Angeline Moonswamy (DDMRI), Callum McGregor (DDMRI), Anna Csala (Oxford), Ajantha Solomon (Melbourne)