TITLE:
Competing Risk Model for Time to Development of Tuberculosis among Adults on Combination Antiretroviral Treatment
AUTHORS:
Lame Sharon Simon, Lesego Gabaitiri, Sikhulile Moyo, Kgalemelo Rodnie Mafa
KEYWORDS:
Adults, Antiretroviral, Development, Risk, Tuberculosis
JOURNAL NAME:
Journal of Tuberculosis Research,
Vol.10 No.3,
September
23,
2022
ABSTRACT: The purpose of this study was to identify factors affecting the time to
development of tuberculosis in the presence of competing risks. In this case
death before developing tuberculosis was deemed a competing risk because it altered
the occurrence of the outcome of interest being time to development of tuberculosis from baseline. We used data from a
randomized longitudinal clinical trial study called the “Tshepo” study. The “Tshepo” study was a 3-year randomized clinical study following 650
ART-naïve adults (69.4% female) from Botswana who initiated first-line NNRTI-based
ART. Participants were assigned in equal proportions (in an open-label,
unblinded fashion) to one of 6 initial
treatment arms and one of two adherence arms using permuted block randomization. Randomization was
stratified by CD4+ cell count
(less than 200 cells/mm3, 201 - 350
cells/mm3) and by whether the participants had an adherence
assistant. Classical methods such as the Kaplan-Meier method and standard Cox
proportional hazards regression were used to analyze survival data ignoring the
competing event(s) which may have been inappropriate in the presence of
competing risks. The idea was to use competing
risk models to investigate how different treatment regimens affect the time to the development of TB and compare the results to those obtained using
the classical survival analysis model which does not account for competing
risks. Amongst 38 patients who died 15.8% of them developed tuberculosis whilst
84.2% of those who died did not develop the outcome of interest. The hazard
ratio of treatment C was 1.069 implying that the risk of developing TB in
patients taking treatment C is about 6.9% higher compared to those taking
treatment A having adjusted for baseline age, baseline BMI, baseline CD4,
Hemoglobin and gender. Similarly, after accounting for competing risks the hazard ratio for treatment C was about
1.89 implying that the risk of developing
TB amongst those taking treatment C was about 89% higher as compared to those taking treatment A. From the
obtained results it was thus concluded that the standard Cox model of time to
event data in the presence of competing risks underestimated the hazard ratios
hence when dealing with data with multiple failure events it is important to
account for competing events.