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New study will investigate how latent co-infections affect clinical outcomes in HIV-infected Kenyan children

African children with delayed HIV diagnosis have a high risk of death, and there is an urgent need for novel strategies to improve their care.  As HIV treatment expands across Africa, Global WACh researchers seek to understand the complex interplay of infectious diseases and HIV infections, which is pivotal to the development of more effective treatments. Dr. Jennifer Slyker (Associate Professor, Global Health; Adjunct Associate Professor, Epidemiology) is leading a new study funded by the National Institute of Health (NIH) to investigate how common, asymptomatic co-infections affect clinical outcomes in critically ill HIV-infected Kenyan children during hospitalization.

The study will examine whether silent infection with Epstein-Barr virus (EBV) and malaria may affect children’s ability to respond to HIV treatment and recover from their illnesses. EBV, the virus causing infectious mononucleosis, infects >90% of the global population but infrequently causes disease in healthy individuals. EBV infection persists through life and there is no vaccine or cure.  Malaria is also endemic in Western Kenya, where most children first encounter infection in early childhood. Once malaria is treated, most children recover and develop some immunity to subsequent infections; however malaria parasites can persist for many years in the blood.

Previous research in this cohort found that reactivation of cytomegalovirus (CMV), another asymptomatic, persistent infection, was associated with worse outcomes in children diagnosed with HIV in hospital. CMV causes dramatic increases in host immune activation, particularly activation of T cells, which may explain poorer outcomes in these children. Like CMV, EBV and malaria also activate the host immune system, but a different type of immune cell is activated in these infections, the B cell. If EBV and malaria similarly affect host immunity and recovery, there may be benefit in addressing one or more of these co-infections when severely-ill children are starting antiretroviral HIV therapy in hospital.

The study continues a >10 year collaboration by UW and University of Nairobi/Kenyatta National Hospital investigators, who have been working together to understand the role of herpesvirus (CMV, EBV, HHV-8, HSV) and tuberculosis (TB) infections in women and children living with HIV infection. The study will use archived blood samples collected from Global WACh’s Pediatric Urgent Start of Highly Active Antiretroviral Treatment (PUSH) Study. Dr. Meei-Li Huang’s lab (UW Virology), will measure EBV viral DNA levels, and Dr. Sean Murphy’s lab (UW Laboratory Medicine,) will use ultrasensitive assays to quantify very low levels of malaria parasites from stored blood samples.

Study investigators include Drs. Grace John-Stewart (UW Global Health; Co-Director, Global WACh), Dalton Wamalwa (Associate Professor, University of Nairobi Paediatrics and Child Health), Irene Njuguna (UW, Kenyatta National Hospital), Barbra Richardson (UW Biostatistics, Global Health), and Sean Murphy (UW Laboratory Medicine).