Dr
Damalie Nalwanga
Project Title
Neurocognitive Function among HIV Infected Infants with Severe Pneumonia Receiving Empirical Treatment for Cytomegalovirus and Tuberculosis (Neuro-Empirical)
EDCTP Project
TMA2020CDF-3198
EDCTP Program
EDCTP2
EDCTP Project Call
Career Development Fellowship (CDF)
Project Objectives
Primary Aim To compare neurocognitive function of HIV infected children with severe pneumonia receiving intervention (empirical treatment for either CMV, TB, or both CMV and TB in addition to standard of care) to those receiving standard of care alone at one year post randomization and at two years of age Secondary Aims 1. To compare the neurocognitive function of HIV infected children with severe pneumonia receiving intervention (empirical treatment for either CMV, TB, or both CMV and TB in addition to standard of care) or standard of care alone to a cohort of HIV positive infants without pneumonia 2. To compare neurocognitive function across all the treatment groups to a cohort of HIV negative children with severe pneumonia at baseline, one year post randomization and at two years of age
Study Design
This prospective longitudinal observational study will be nested under the EMPIRICAL study, a randomized open label clinical trial among HIV positive children under 1 year of age with severe pneumonia. We will additionally recruit and enroll a longitudinal cohort of HIV negative children with severe pneumonia, as well as a cross-sectional cohort of HIV positive children without pneumonia.
Project Summary
The EMPIRICAL study is a randomized, factorial open label clinical trial investigating survival of HIV positive children under 1 year of age with pneumonia. It will randomize these children to receive empirical treatment for either CMV pneumonia, or TB, or both in addition to standard of care treatment for pneumonia with the aim of reducing mortality from undiagnosed CMV and TB. The control arm will receive only standard of care treatment of pneumonia. Whereas the children who receive empirical treatment for CMV and TB could have reduced mortality, it is imperative to maximize their neurocognitive function in order to enable them become more productive and realize their full potential as adults. Following the Sustainable Development Goals (SDGs) which call for extending the focus of child health initiatives beyond reducing mortality to reducing morbidity and improving quality of life, we propose a project (Neuro-Empirical study), nested within the EMPIRICAL study, to investigate differences in neurocognitive outcomes among children randomized to intervention versus control. It will investigate the possibility of a neurocognitive advantage of empirical treatment of CMV and TB over standard of care treatment. The primary aim is to compare neurocognitive function of HIV infected children with severe pneumonia receiving intervention (empirical treatment for either CMV, TB, or both CMV and TB in addition to standard of care) to those receiving standard of care alone at one year post randomization and at two years of age. Eligible participants who give informed consent will be consecutively enrolled into the study. A pre-tested questionnaire will be used to collect participants’ baseline data including age, sex, a detailed anthropometric assessment (weight, length, weight for length z score and head circumference), duration on ART for those who will have already started ART, ART exposure in utero, treatment adherence using 3 day recall, history of prematurity, prior hospitalization and laboratory findings including hemoglobin, CMV viral load, HIV viral load and CD4 cell count. Other independent variables will include birth history (birth weight and history of requiring resuscitation), caretaker data (relationship with child, level of education, depression score), and family socio-economic status. At one year post randomization and two years of age, a follow-up questionnaire will be applied evaluating caretaker data, socio-economic status, and anthropometric measurements. Controls will be recruited in parallel (within 15 days), and receive the same questionnaires. Neurodevelopmental assessments will be done at baseline (at discharge from hospital since they will be stable enough to do the neurocognitive tests), at one year post randomization to receive assigned intervention (empirical treatment for CMV, TB, or both i.e. cases) or no intervention (controls) to establish the trend of neurocognitive function, and at two years of age. A window of ±3 weeks will be applied for the baseline and year 1 assessments. A window of -3 months will be applied to the 2 years of age assessment to allow for timely completion of the fellowship . We are interested in evaluating differences between cases and controls at baseline, and two years. The neurodevelopmental deficits that persist until one year and beyond are more likely to reflect clinically significant impairment. Neurodevelopment will be assessed using the Bayley Scale of Infant and Toddler Development III.
Host Organisation
| Department | Institution | Country |
|---|---|---|
| Makerere University | Uganda |