Development and Implementation of a Cost-Effective Diagnostic Algorithm to Reduce AIDS-Related Deaths among Hospitalized People with Advanced HIV Disease - PROJECT SUMMARY / ABSTRACT Advanced HIV disease (AHD, defined as CD4 cell count <200 cells/µL) remains a major public health concern despite expanded access to antiretroviral therapy. People with AHD remain at high risk for avoidable opportunistic infections (OIs), hospitalization, and death, with inpatient mortality ranging from 20% to 44%. In resource-limited settings, cost constraints and supply shortages force healthcare workers to make critical treatment decisions based on limited diagnostic information. This approach results in frequent presumptive tuberculosis (TB) diagnoses, risking underdiagnosis of other clinically significant OIs, such as Pneumocystis pneumonia, histoplasmosis, and chronic pulmonary aspergillosis. Point-of-care diagnostic assays for these OIs and inflammatory biomarkers like C-reactive protein (CRP) remain underutilized in this population and may offer opportunities to improve triage and facilitate diagnosis among hospitalized people with AHD. The objective of this F30 application is to develop and implement a diagnostic algorithm to facilitate the cost- effective identification of pulmonary OIs among hospitalized adults with AHD in Uganda, and to evaluate the dynamics of serum CRP in this population. The central hypothesis is that a diagnostic algorithm that prioritizes inexpensive point-of-care diagnostics for prevalent OIs will increase diagnostic accuracy, shorten hospital duration, and reduce in-hospital mortality. In Aim 1, a decision analytic model will be developed to identify a cost-effective diagnostic algorithm for hospitalized adults with AHD and symptoms of a pulmonary infection. This algorithm will incorporate the local epidemiology of pulmonary OIs in Uganda and the performance and cost of novel point-of-care tests. In Aim 2, the diagnostic algorithm will be implemented among hospitalized adults with AHD and symptoms of pulmonary infection in Uganda to evaluate the performance of the algorithm in a real-world setting. The primary outcome will be the proportion of participants with a microbiologically confirmed diagnosis. Secondary outcomes will include OI prevalence, time to confirmed diagnosis, hospital length of stay, vital status at hospital discharge, algorithm adherence, and barriers to adherence. In Aim 3, serum CRP dynamics will be evaluated among hospitalized adults with AHD. Findings from these aims will address a critical gap in AHD care, as identified by the World Health Organization, and have the potential to reduce preventable deaths, optimize healthcare resource allocation, and contribute to the evidence base informing future international guidelines for the care of hospitalized people with AHD in resource-limited settings. Through this work, the applicant will gain skills in decision analysis, cost- effectiveness analysis, and the implementation and evaluation of diagnostic strategies in resource-limited settings, all essential for their development as an independent physician-scientist with expertise in clinical and global epidemiology.
