Earlier ART treatment for children with HIV in Africa leads to stronger immune systems in adulthood

In a study funded by the Medical Research Council (MRC), the Engineering and Physical Sciences Research Council (EPSRC), the Department for International Development (DFID) and Great Ormond Street Hospital (GOSH) Biomedical Research Centre, researchers have shown that starting children with HIV in Africa on antiretroviral treatments before the age of six increases their likelihood of not just surviving into adulthood, but surviving with a stronger immune system. 

These results provide important information to help in the development of international guidelines on HIV treatment for children.

The team, led by Joanna Lewis from UCL in collaboration with UK, Ugandan and Zimbabwean investigators, analysed immunological data from a clinical trial called ARROW which looked at 1,206 children in Africa with HIV given anti-retroviral treatment (ART). They found that children started on ART under the age of six develop a stronger immune system than children who start treatment at an older age, probably in part because young children have a very active thymus, a key organ for the immune system.

They also found that, as a result of immune system damage and declining thymic activity, for each year that goes by after the age of six, the capacity for the immune system to recover declines. If therapy is delayed until after 10 years of age, children are unlikely to make as strong an immune recovery as when they are younger. This is particularly important for doctors looking to mitigate effectively the damage to a child’s immune system and optimise recovery.

The ARROW trial, which was coordinated by the MRC Clinical Trials Unit at UCL, looked at questions around how best to treat children with HIV in Africa. It followed 1,206 children in Uganda and Zimbabwe for five years. The team used data from the trial to develop a mathematical model where children’s CD4 white blood cell count (a critical measure in the immune system) in combination with their age can predict their corresponding CD4 count as an adult.

Dr Joanna Lewis at UCL, who led the study, said: “It is becoming increasingly clear that how we manage all aspects of the care of children with HIV will determine the quality of their lives as adults. This study provides an important steer as to when anti-retroviral therapy needs to be started to optimise immune recovery required for long-term health and quality of life.”

Professor Robin Callard, one of the senior authors, said: “Developing this model has provided important insights into the way children respond to ART and will identify other factors that could be important in determining the quality of immune recovery as children grow up.”

Professor Nigel Klein, a senior author on the paper and paediatrician looking after children with HIV at Great Ormond Street Hospital, said: “The success of anti-retroviral therapy means that we now expect most children who start on therapy to survive into adulthood. This work marks a change in our thinking from treatment guidelines based upon reducing the short-term risk of dying to optimising the quality of the immune system when children become adults. This work has already altered the management of children in our hospital.”