Default Time from Tuberculosis Treatment in the Southern Republic of Benin Using Mixture Cure Model for Survival Analysis

Abstract

Background: To date, this is the first statistical analysis of default time from tuberculosis (TB) treatment conducted in the republic of Benin. This cohort study assessed the cured fraction, the conditional probability of default (CPD) from treatment course and identified the risk factors predicting its timing. Methods: TB case was a patient with positive culture for the Mycobacterium tuberculosis complex or with two sputum smears positive for acid-fast bacilli. The 2008’s cohort of TB patients was extracted from Benin national TB registry. Active TB Patients who were diagnosed between November 2007 and December 2008 were included and followed up to December, 23 rd 2009 relative to their specific initiation date. Default was defined using the WHO guidelines. Primary endpoint was the time to default from the anti-TB treatment course. Risk factors were assessed with univariate and multivariate Cox regression integrating the mixture cure models. Results: More than 5% (n=64) of defaulters were identified with a cured fraction of 94.1%. About 3% of patients defaulted within the first 2 months (CPD = 0.025 ± 0.004). HIV/AIDS co-infection and TB history were independently associated with default time (log-rank = 35.21; P < 0.0001 and log-rank = 10.11; P = 0.0015 respectively). With Cox proportional hazards (PH) analysis, predictors of default time were HIV/AIDS, TB history and Age (hazard ratio [HR] = 3.82 [2.28; 6.41], P < 0.0001 for HIV-positive, HR = 0.13 [0.03; 0.53], P = 0.0045 for previous-TB infection and Age (HR = 3.49 [1.25; 9.74], P = 0.0170 for 65 years old or more, respectively). With logistic Cox PH mixture cure model HIV/AIDS and Age significantly increased the probability of default (Odds Ratios [OR] = 4.04 [2.64; 7.08], P < 0.0001 for HIV-positive, and OR = 4.23 [1.58; 12.10], P = 0.006 for 65 years old or more, respectively) whereas TB history significantly reduced default probability (OR = 0.04 [0.004; 0.54], P = 0.0148 for previous-TB infection. Conclusion: Whatever the alternative model considered, this study provides the first evidence that HIV/AID, TB history and Age were the major predictive factors of default time from anti-TB treatment in Benin. Therefore, additional efforts to improve the compliance of patients with anti-TB treatment through a better management of the co-infection with HIV/AIDS in accordance with patient’s specific age group may be an important feature of a prospective TB control strategy in the future. This should be emphasized in the early treatment course for these subgroups of TB patients.