Competing risks multi-state model for time-to-event data analysis of HIV/AIDS: a retrospective cohort national datasets, Ethiopia

Abstract

Introduction: Tuberculosis (TB) remains the most common opportunistic infection and leading cause of death among individuals living with HIV/AIDS in Ethiopia. Its significant impact on morbidity and mortality underscores the crucial link between these two diseases. While the advent of antiretroviral therapy (ART) has led to a dramatic decline in mortality rates among HIV/AIDS patients, TB continues to pose a substantial threat. This study aims to estimate the probability of death due to TB among HIV/AIDS patients on ART, considering the presence of various competing risks, including diarrhea, other infections, and unknown/unspecified causes. Also we have assessed the effects of prognostic factors on HIV/AIDS cause specific deaths, compared with the death from other competing risks, and exploring leading cause of death among HIV/AIDS patients on Antiretroviral Therapy.

Methods: Data from a retrospective research examining the effectiveness of antiretroviral therapy (ART) in Ethiopia were used in this investigation. The data came from medical records of patients who were part of the national ART program. A total of 39,590 records were gathered between October 2019 and March 2020 from all regions of Ethiopia as well as the administration cities of Addis Ababa and Dire Dawa. The study facilities were grouped using a multi-stage sample technique and simple random selection was used to select health facility and a person record from medical records. In the presence of the competing causes of death, Cause specific hazard, subdistribution hazard model and flexible parametric proportional hazard model have been used to assess the effect of covariates on the risk of death, with the cmprisk package in R4.3.2 software.

Results: Out of the total 1212 deaths, 542(44.7%) died competing with other opportunistic infection (TE-Esophageal Candidiasis, TO-oral, CT-CNS Toxoplasmosis, CM-Crypotococcal Meningitis…), 421 (34.7%) died due to tuberculosis and the remaining death were unknown/Not specified infection 222(18.3%) and diarrhea 27(2.2%). Rates of mortality caused by tuberculosis, competing with other opportunistic infection, diarrhea and unknown/Not specified were 3.5, 4.5, 0.2 and 1.8 per 1000 person-months, respectively. Having a higher CD4 count at diagnosis, responding to combination antiretroviral treatment (cART) six months after start, and having prophylactic treatment for pneumocystis pneumonia (PCP) decreased the risk of tuberculosis, other opportunistic infections, and unidentified and diarrheal causes of death. However, older age, late HIV.AIDS diagnosis, and the last HIV/AIDS WHO clinical stages increased the hazard of tuberculosis and other opportunistic disease mortality. Additionally, male gender, older age and last HIV clinical stages increased the mortality HIV/AIDS patients.

Conclusion: The findings of this study demonstrated that TB, an opportunistic infection, was the primary cause of death in HIV/AIDS patients, despite the presence of several competing risks, such as diarrhea, other infections, and an undetermined or unclear cause. It's important to use effective techniques to quickly detect those who have HIV or AIDS and provide them with care and treatment to increase their chances of surviving.

Keywords: AIDS; Competing risk; Cumulative Incidence Function; ·Cause-specific hazard; ·Sub-distribution hazard.

Fig. 1

Title competing risks model with and death as causes of failure (a). legend Illness-death model with an initial state of illness state and a death state (b)

Fig. 2

Competing Risks Model for HIV/AIDS Patients Receiving ART

Fig. 3

Non-parametric and parametric estimate of cumulative incidence functions. A Non-parametric estimates of cumulative incidence functions for deaths from TB (status==1) Diarrhea (status=2), other Opportunistic Infection (status=3) and unknown causes (status=4).Each outcome is compared between male and female patients. B Estimate cumulative incidence in the presence of TB death, Diarrhea, Other OI & Unknown. C & D Parametric estimates of cumulative incidence functions for three patients with given covariate

Fig. 4

Estimated Cumulative Incidence Function for Tuberculoss, Other OI, and Unknown/Unspecified and Diarrhea Causes of Deaths of HIV/AIDs Patients by cd4 cell count using Cause Specific Hazard Models (A;TB, B:Other Infection, B: Unknown/Unspecified, and D:Diarrhea Causes)