Causes of mortality among tuberculosis and HIV co-infected patients in Chiang Rai, Northern Thailand

Pacharee Kantipong,¹ Kuniko Murakami,² Saiyud Moolphate,³ Myo Nyein Aung,^4,5 Norio Yamada<sup>2

1</sup>Chiang Rai Prachanukroh Hospital, Thailand; ²Japan Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan; ³TB/HIV Research Project, Chiang Rai, Thailand; ⁴Department of Public Health, Graduate School of Medicine, Juntendo University, Tokyo, Japan; ⁵Department of Epidemiology, University of Public Health, Yangon, Myanmar

Background: The case fatality rate in patients with tuberculosis (TB) associated with human immunodeficiency virus (HIV) has been particularly high in Chiang Rai, Northern Thailand. It was almost 50% before the introduction of antiretroviral therapy in the last decade, and was still at 28% in 2008, despite expanding access to antiretroviral therapy. Reviewing the causes of death may lead to further understanding of the timeline and natural history of TB-HIV coinfection, and in so doing help to devise an effective prevention strategy in Chiang Rai. In this study, we aimed to investigate the distribution of confirmed causes of death in patients coinfected with TB and HIV in Chiang Rai, describe the causes of such deaths along the timeline of TB treatment, and identify predictors of each cause of death.
Methods: In this retrospective study, we reviewed the causes of death for 331 patients who died of TB-HIV coinfection at Chiang Rai Prachanukroh Hospital from 2005 to 2008. Causes of death were confirmed by reviewing medical records, vital registration, and the TB register in the province, as well as obtaining reconfirmation by two experienced HIV physicians.
Results: The confirmed causes of death were TB (39%), acquired immune deficiency syndrome (AIDS)-related opportunistic infections other than TB (AOI) (29%), and other systemic diseases which were neither TB nor AIDS-related opportunistic infections (nonTB-nonAOI) (16%). The definitive cause could not be confirmed in the remaining 16% of deaths. After starting the TB treatment, deaths caused by TB occurred earlier compared with deaths caused by AOI, which occurred steadily throughout the course of TB treatment, whilst deaths caused by non-TB-nonAOI increased gradually in later months. Further analysis by multivariate multinomial regression analysis showed that deaths in the first month (adjusted odds ratio [aOR] 4.64, 95% confidence interval [CI] 2.49–8.63), CD4 count ≥ 200 cells/mm³ (aOR 5.33, CI 1.05–26.10), non-category 1 TB treatment regimens (aOR 5.23, CI 1.04–9.77), and TB meningitis (aOR 3.27, CI 1.37–7.82) were significant predictors of confirmed TB deaths. Moreover, age over 45 years (aOR 3, CI 1.32–6.84) and admission as an inpatient were predictors of death caused by neither TB nor AIDS-related opportunistic infections (aOR 3.08, CI 1.39–6.80). Additional analysis showed that non-Thai patients (aOR 0.35, CI 0.12–0.99), those with an unknown CD4 count at TB diagnosis (aOR 0.16, CI 0.08–0.33), and those without an HIV diagnosis before TB treatment (aOR 0.32, CI 0.18–0.59) were less able to access antiretroviral therapy.
Conclusion: The timeline and predictors of causes of death may assist in devising an intervention strategy for further reduction of the TB-HIV case fatality rate.

Keywords: human immunodeficiency virus, tuberculosis, coinfection, cause of death, CD4, antiretroviral therapy