Abstract:
Background: Co-infections with Human Immunodeficiency Virus and Tuberculosis are
extremely taxing on health care systems and present unique diagnostic and treatment difficulties.
TB is the most frequent cause of mortality from HIV patient. Thus, Mycobacterium tuberculosis
and HIV work together to accelerate the reduction of immune system. The objective of this study
was joint modeling of bivariate longitudinal outcomes and time to death of HIV/TB co-infected
patients at University of Gondar Comprehensive Specialized Hospital, North West Ethiopia.
Methods: A retrospective cohort study was conducted with data from 192 HIV/TB co-infected
patients, covering the period from September 1, 2014, to September 1, 2024. The analysis
utilized Cox proportional hazards models for survival outcomes and linear mixed-effects models
for longitudinal data, focusing on CD4 cell count and weight changes. A joint model was
constructed to assess the correlation between these longitudinal markers and survival outcomes.
Result: The cox proportional hazards model indicated that functional status significantly
impacted mortality among HIV/TB co-infected patients, with ambulatory and bedridden
individuals having hazard ratios of 1.721 (p = 0.005) and 1.694 (p = 0.008), increased risk of
death compared to worker patients, respectively. Patients in WHO stage IV had a 1.239-fold
increased risk of death compared to those in stage I (p = 0.003). In the linear mixed effects
models, changes in CD4 cell count were significantly influenced by age (-0.002, p = 0.036) and
treatment adherence (0.122, p = 0.029). The joint modeling analysis revealed a significant
negative association between the natural log of CD4 cell count and mortality risk (association
parameter = -0.613, p < 0.0001), indicating that higher CD4 counts are linked to lower
mortality risk.
Conclusion: In the joint model analysis patients with functional status, WHO stage, religion, and
marital status had significant factors for time to death of HIV/TB co-infected patients. And age,
WHO stage, functional status, opportunity infected, adherence, smoking status, occupation and
visiting time were significant factors of CD4 cell count of patients. As a recommendation, to
reduce the risk of death, the government health agencies and healthcare centers should provide
nutritional and psychological support for functional status of ambulatory and bedridden
individuals.
Keywords. Joint model, HIV/ TB co-infected, CD4 cell count, Weight, LMM, Survival
