There are an estimated 1.7 million children living with HIV globally, with approximately 90% in sub-Saharan Africa. Despite antiretroviral treatment, many of these children remain susceptible to vaccine-preventable diseases, including measles. Consequently, the World Health Organization?s Strategic Advisory Group of Experts (SAGE) on immunization recommended in 2015 that children living with HIV and receiving treatment be revaccinated against measles. With earlier diagnosis in infancy in recent years, children living with HIV may now be initiating treatment prior to measles vaccination at 9 months of age. The impact of this change in the relative timing of measles vaccination and treatment on short and long-term immunity to measles is not fully known. SAGE found that there was insufficient evidence to make recommendations for children who start treatment before measles vaccination and identified this as a research priority. This proposal will bring together a team of institutions and investigators to address this gap and evaluate the short and long-term impact of early treatment initiation on antibodies to measles among children living with HIV in Zambia. The proposed research aligns with the priorities of the National Institute of Allergy and Infectious Diseases to better understand immune responses to infectious diseases and to foster international scientific collaborations. The studies will be conducted at an established research site in rural southern Zambia and will be nested within two ongoing studies: 1) a long-standing cohort study of children living with HIV and receiving care at an HIV clinic; and 2) a community-based study of malaria. The proposed studies will test stored samples collected from these studies for measles antibodies to address the research questions.
For Aim 1, samples collected 6-12 months after treatment initiation will be tested from children younger than 5 years of age and enrolled in the pediatric HIV cohort. The level of measles antibodies will be compared across participants initiating treatment at different ages (<9 months of age and prior to measles vaccination, 9 months to 1.9 years of age, and 2.0 to 4.9 years of age).
For Aim 2, samples collected from children enrolled in the community-based malaria study will be tested to serve as an age-matched HIV-uninfected control group for children tested in Aim 1. The level of measles antibodies will be compared between HIV-infected and uninfected children.
For Aim 3, samples collected from participants in Aim 1 will be tested up to 4 years after treatment initiation. Long-term changes and trajectories of antibody levels over time will be compared across participants initiating treatment at different ages. The proposed studies will fill key gaps in our understanding of short and long-term immunity to measles virus among children living with HIV and initiating treatment before and after measles vaccination. The findings from the proposed studies will contribute to the scientific evidence on which to base recommendations for measles revaccination among children living with HIV in the era of early treatment initiation to ensure that children receive optimal care and remain protected from vaccine-preventable diseases.
Children living with HIV are now starting treatment at earlier ages, potentially prior to measles vaccination and disease progression, and the impact of this change in the relative timing of measles vaccination and treatment on measles immunity is not fully understood. The proposed research will build on existing studies in rural Zambia to evaluate the impact of early treatment initiation on short and long-term immunity to measles. These studies will fill key gaps in our understanding of measles immunity in the current era of early treatment initiation, and will be critical for developing appropriate recommendations on measles revaccination for children living with HIV to ensure that they are protected from vaccine-preventable diseases.
