Authored by Kebede Embaye Gezae*
Abstract
Background: Ethiopia is a country with high burden of tuberculosis and human immunodeficiency virus (TB-HIV) dual infections in the world. However, little was known so far on predictors of time to death among TB/HIV co-infected adults in the study setting in particular. Therefore, this study was aimed at filling this gap in the region particularly.
Methods: A hospital based retrospective cohort study design was employed on 305 Tuberculosis and Human Immunodeficiency Virus (TB/ HIV) co-infected adults who have started Anti-Retroviral Therapy (ART) from January 2009 to December 2016 at two governmental hospitals in Mekelle, Ethiopia. Multivariable cox regression analysis was applied to identify statistically significant predictors of time to death (P ≤ 0.05). Finally, Adjusted Hazard Ratio (AHR) and 95% Confidence Interval (CI) were interpreted and reported in the final cox model.
Results: Overall, 70 of 305 (23.0%) TB/HIV co-infected adults were died during the entire follow-up period. The study subjects (257 Active TB, 48 Latent TB) were followed for an overall median follow up time of 37 months (Interquartile Range: 10-63 months). Baseline Body Mass Index (< 18.5 kg/m2) (AHR=2.427; 95% CI: 1.214 - 4.853) and Being Extra-pulmonary TB (Mixed TB) patient (AHR=2.400; 95% CI: 0.220-0.697) were predictors of time to death. On the other hand, increasing CD4 cell count (AHR=0.995; 95% CI: 0.991-0.999), developing drug side effects (AHR=0.369; 95% CI: 0.194–0.701), being co-infected with Latent TB infection (AHR=0.102; 95% CI: 1.023-0.449), completing TB treatment (AHR=0.114; 95% CI: 0.060–0.16), and being on Cotri-moxazole Prophylactic Therapy (AHR=0.391; 95% CI: 1.348, 4.273) had prolonged the time to death.
Conclusions: Almost one-fourth of TB/HIV co-infected patients were died with a relatively high mortality rate among those co-infected with active TB since ART initiation. Moreover, being co-infected with active TB/HIV, having low baseline BMI (≤ 18.5 g/dl), Low CD4 cell count, not developing drug side effects, being on TB treatment, and being off CPT were shortening the time to death. Therefore, efforts have to be made to reduce malnutrition and active-TB/HIV co-infection associated accelerated mortality.
Keywords: lts; Time to death; TB/HIVforecasting
Abbreviations: AHR: Adjusted Hazard Ratio; ART: Anti-Retroviral Therapy; BMI: Body Mass Index; CPT: Co-trimoxazole Preventive Therapy; CHR: Crude Hazard Ratio; CI: Confidence Interval; EPTB: Extra-Pulmonary Tuberculosis; HIV: Human Immunodeficiency; Virus HR: Hazard Ratio; IPT: Isoniazid Preventive Therapy; IQR: Interquartile Range; LTBI: Latent TB Infection; OI/s: Opportunistic Infection; PLWHIV: People Living with HIV; PMs: Person Months; PTB: Pulmonary Tuberculosis; SSA: Sub-Saharan Africa; TB: Tuberculosis; WHO: World Health Organization
Introduction
Tuberculosis (TB) is the most common opportunistic infection among People Living with Human Immunodeficiency Virus (PLWHIV), and persons co-infected with HIV and TB are highly vulnerable to death as a result of the bidirectional relationship and synergism of the two infections [1]. The risk of death in co-infected individuals is also approximately twice that of HIV infected individuals alone even considering CD4 cell count and Anti- Retroviral therapy (ART) into account [2]. HIV is the first and TB is the second leading cause of death from infectious disease statistics world widely. Globally, above one-third of the world population were estimated to be latently infected with TB [3]. In the year 2014, above 9 million people developed TB, of which 12% were co-infected with HIV [4]. In 2015, 33 % of HIV deaths were due to TB evidencing that it is still a leading cause of mortality among PLWHIV [5].
Similarly, retrospective cohort studies employed in different parts of Ethiopia have been reported. The positive relationship between HIV and TB. For instance, a retrospective cohort study in Ethiopia has reported that 9.0% of HIV patients on ART were estimated to develop TB [6]. Another study from Amhara region, Ethiopia has also revealed that above one-fourth of HIV patients on ART were co-infected with TB [7]. Another study took place in Bahir Dar reported almost one –third of TB patients were also experienced to have HIV and above one-fifth of the TB-HIV cases were fatal [8]. Furthermore, accelerated TB/HIV deaths were significantly associated with low baseline CD4 cell count, ambulatory or bedridden functional status, low baseline weight, advance baseline clinical stage, absence co-trimoxazole prophylaxis (CPT), and co-existence of other OIs in most of the studies [6-12].
According to the national annual performance report of Ethiopia, the ART coverage of TB/HIV co-infected patients was as low as 70% [13]. However, the predictors of accelerated mortality of TB/HIV co-infected patients were not yet fully investigated. Thus, this study was aimed at investigating predictors of accelerated mortality of TB/HIV co-infected patents in the study setting, in particular.
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