PedMAb: a project with paradigm-shift potential
June 2021, an international team of researchers had a kick-off meeting for a new EDCTP research project undertaking a study that represents a paradigm shift in mother-to-child-transmission of HIV. CIH Professor Thorkild Tylleskär is a member of the team.
Preventing children from getting HIV from their mothers
Vertical transmission / mother-to-child-transmission (MTCT) of HIV is one of the great tragedies of the AIDS epidemic. MTCT may occur at several points: during pregnancy (intrauterine), during birth (intrapartum) and during breastfeeding.
Early effective preconception and antenatal antiretroviral therapy (ART) reduces MTCT. For this reason, public health policies have been implemented whereby mothers are strongly encouraged to attend pre-natal clinics where, among other things, they are tested for HIV. ART and pre-exposure prophylaxis (Pre) therapies are distributed free of charge and have significantly reduced MTCT during pregnancy and birth.
Despite these measures, the rate of MTCT of HIV from breastfeeding is increasing relative to the other causes of MTCT. While the absolute number of cases of MTCT acquired through breastfeeding is decreasing, the rate of decrease is less than the decreases being achieved during pregnancy and birth.
Why are women and infants still acquiring HIV despite universal testing and treatment (UTT)-based PMTCT being available?
- HIV testing is only routine early in pregnancy. There is no routine testing for late maternal HIV acquisition (during the third trimester of pregnancy or post-partum).
- For various reasons, mothers may not avail themselves of the free HIV-testing opportunities early in their pregnancy and so have a chronic untreated maternal HIV infection.
- For various reasons, mother may have suboptimal postnatal adherence to the free-of-charge maternal ART.
Thus, urgent action is needed to evaluate and implement additional preventive strategies to reduce MTCT in high HIV prevalence and incidence settings. These include biomedical strategies such as active (vaccine) or passive immunoprophylaxis with long-acting broadly neutralising antibodies (bNAbs).
The use of biomedical strategies represents a paradigm shift in the paediatric HIV/AIDS epidemic. The formulations are potent, long acting, and injectable, and thus have indisputable potential for protection from MTCT HIV. However, they are also new and represent a knowledge gap. This research project intends to address this issue in the hope of collecting data that can be used to conduct larger trials, ultimately influencing public health policy, and reducing MTCT.
PedMAb’s goal is to define the optimal dose(s), timing, and the ideal combination(s) of bNAbs to prevent HIV breast-milk transmission in high-incidence regions.
PedMAb’s FIRST OBJECTIVE is a multi-step approach phase I (dose finding) study followed by a phase II study to test the bNAbs’ safety, tolerability and pharmacokinetic (PK) profile.
The bNAbs will be administered subcutaneously (SC) alone or in combinations to breastfeeding, HIV-exposed, uninfected (HEU) neonates (within 72h of birth) alongside the standard-of-care ART. The bNAB administration will be repeated in the infants at 4 or 6 months.
The clinical trials and associated research questions will form an excellent basis for knowledge, technology transfer, quality assurance programs and training between consortium partners and contribute to capacity building. This capacity building and strengthening is the SECOND OBJECTIVE of the study.
The trials will be implemented at the South African Medical Research Council’s Chatsworth accredited Clinical Research site, located at RK.Khan regional hospital, Durban. There are 2000-2300 deliveries by HIV-infected women/year at this hospital. The HIV-prevalence among pregnant women in this district is approximately 46%, and the exclusive breastfeeding prevalence is around 64% among HEU aged 0-14 weeks.