Breakthrough tuberculosis disease among people with HIV – Should we be worried? A retrospective longitudinal study

INTRODUCTION: Isoniazid preventive therapy (IPT) is a proven means to prevent tuberculosis (TB) disease among people living with HIV (PLHIV). However, there is a concern that patients often develop tuberculosis disease while receiving IPT, defined here as breakthrough tuberculosis, which may affect treatment outcome. In this study, we assessed the magnitude and determinants of breakthrough tuberculosis. METHODS: A multisite retrospective longitudinal study from the year 2005 to 2014 involving 11 randomly selected hospitals from the Addis Ababa, SNNPR (Southern Nations Nationalities and Peoples Region), and Gambela regions of Ethiopia was carried out to assess the occurrence of breakthrough tuberculosis. Cox regression analysis was used to study factors associated with breakthrough TB. RESULTS: 4,484 patients in chronic HIV care received IPT. Eighty percent of the same number received antiretroviral therapy (ART). Tuberculosis developed in 88 of 4,484 (2%) patients of which 24 (0.5%) were diagnosed while receiving IPT. Breakthrough TB incidence was 1106 per 100,000 person-years (PY) (95% CI: 742–1651) while TB incidence after completing IPT was 624 per 100,000 PY (95% CI: 488–797). Seven of the 24 (29%) breakthrough TB cases were diagnosed within the first month of IPT initiation. Of 15 patients who developed breakthrough TB while on ART, nine (60%) were diagnosed within the first six months of ART initiation. Having high CD4 cell count and being on ART were associated with having lower risk of developing TB and breakthrough TB. CONCLUSION: Breakthrough TB was uncommon in the study setting. Even then, taking ART reduced the risk of its occurrence. Slightly more than a quarter of the cases of breakthrough TB occurred in the first month of treatment and may be existing undiagnosed TB cases which were missed during diagnostic work-up.