Developing and Validating an Inclusive and Cost-Effective Prediction Algorithm for Survival and Death Among People Living With HIV in Sub-Saharan Africa: Protocol for a Meta-Analysis and Case-Control and Cost-Effectiveness Study

Abstract

Background Premature death in people with HIV in sub-Saharan Africa (SSA) is highly preventable. However, the lack of inclusive, cost-effective prognostic tools remains challenging. Most prognostic tools have been developed in high-income economies. The distinct cultural dynamics in HIV-related death epidemiology makes them unsuitable for the region. Additionally, the models lack systematic stratification of death determinants based on clinical relevance, and some included factors are too expensive for people with HIV in SSA. Objective We aimed to create a tailored predictive model that considers the unique context of SSA, including cultural dynamics, cost-effectiveness, and clinical relevance. Methods This is a 2-phase study. In the development phase, we will use a combination of evidence synthesis, namely meta-analysis, application epidemiology, biostatistical, and economic paradigms, to develop a prognostic model for people living with HIV in SSA. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) protocol will be followed in the structuring of the meta-analysis. From their creation to the present, we will search African journals (Sabinet) and the PubMed, Scopus, MEDLINE, Academic Search Complete, Directory of Open Access Repository, Cochrane Library, Web of Science, EMBASE, and Cumulative Index for Nursing and Allied Health Literature databases. Only cohort studies with moderate to high quality will be included. The primary outcome variables include the predictors of HIV-related death and their corresponding effect sizes (adjusted relative risk). A random-effect meta-analysis model will be used to synthesize the unbiased estimate of risk (relative risk) per predictor. Epidemiological metrics such as risk responsiveness, geotemporal trend, risk weight (Rw), clinical minimum important difference (CMID), predictors interaction density (PID), critical risk points, and potential cost implication will be computed. A combination of Rw and CMID will be used for risk stratification. The model’s constituent items will be selected based on the combination of Rw, CMID, PID and cost implication. In the validation phase, we will apply the emergent model to classify participants using a secondary data obtained from a cohort of people living with HIV in East and West Africa, with outcomes including sensitivity, specificity, calibration, and area under the receiver operating characteristic curve (AUC). Results The study is projected to commence in October 2025 and end in September 2026. The expected result will be published in November 2026. The result will be presented using narrative and quantitative synthesis. Indices of causality namely as strength of association, temporality, consistency, biological gradient, and specificity of the predictor-outcome association will be presented in a tabular format. TheAUC will be used to decide the optimal critical risk point for the emergent predictive algorithm. Conclusions Effective prognostication coupled with intense monitoring and evaluation, and prioritizing of therapeutic targets could positively turn around the fate of millions of people living with HIV at risk of premature death in SSA. Trial Registration PROSPERO CRD42023430437; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023430437 International Registered Report Identifier (IRRID) PRR1-10.2196/63783