A global look at HIV-Exposed Uninfected children

Andy Prendergast came along to our annual conference to talk about those children who have been exposed to HIV but are uninfected, the health implications for this group and how this is being addressed around the world.   

HIV-Exposed Uninfected Children (HEU) face an increased risk of morbidity and mortality, despite not being infected with HIV themselves. There are around 15 million HEU children worldwide, with the majority in South Africa, Uganda, Mozambique, Tanzania, and Nigeria. 

The story began about 30 years ago, Andy told us from the main stage, when reports started to emerge from Sub-Saharan Africa of an increased risk of morbidity in babies born to women with HIV but who were themselves HIV-uninfected. The biggest study came from Zimbabwe, where at two years of age, there was a threefold increase in mortality for exposed uninfected babies compared to those born to women without HIV. The causes of death were similar to those of infected babies, and predictors were highly related to maternal disease status. 

Even despite the scale-up of antiretroviral therapy (ART) in 2002, this is still an ongoing problem, with a 60-70% increased risk of mortality seen in HEU children at every age stratum. Several factors account for 66% of this mortality: the mother never initiating breastfeeding, the mother not receiving three-drug ART for life, the mother having passed away, and the child having a low birth weight. 

Three more studies in high income countries have shown there was an increased risk of infections in this cohort, including for Group B streptococcal infections. Also, in Zimbabwe, an increased risk of stunting and general undernutrition have been seen in this HEU group, due to less growth in-utero. There is also evidence of lower developmental scores for these children e.g. in expressive language and motor skills. 

Why are HEU children more at risk?

There are several reasons for the increased risk of morbidity and mortality in HEU children. The first is the effect of HIV or other co-infections, the second is the drugs the mother may be taking, and the third is socioeconomic or other universal risk factors. There is definitely a footprint on the foetus because of the maternal infection, due to inflammatory cells, mediators, and other antigens.

Lower transplacental antibodies and pathogens, including those against vaccine-preventable infections, have also been observed. This means the baby isn’t getting topped up with passive protection from a mother who’s been vaccinated, which may be particularly important in the first six months of life. 

What can be done to prevent these outcomes?

Early treatment and better overall maternal health seem to be critical in improving the outcomes for HEU children. Breastfeeding may also be an essential factor; if infants can be breastfed early and exclusively, and women are in good health by starting early ART, this seems to minimise the risk.

Intervention strategies for this issue include: early HIV diagnosis, lifelong suppressive ART, and support with taking medication. It’s also important to think about interventions at both the antenatal and postnatal stages. A comprehensive package of interventions has also been shown to help, including infant feeding with supplements, and improving water, sanitation, and hygiene (WASH). When we trialed this package, it helped reduce stunting from 50-40% and helped children achieve better developmental scores at 18 months of age.

Overall, HEU infants face more morbidity, mortality, and severe infections, and primarily in Sub-Saharan Africa. Breastfeeding and maternal disease severity are definite risk factors. A comprehensive package of interventions, including nurturing care that considers all elements to ensure healthy growth and development, is necessary to address the package of risk factors effectively. Early treatment and better maternal health are also critical to improving outcomes.