Mortality in TB/HIV Patients
Mortality in TB/HIV Patients
Background: Tuberculosis-HIV (TB-HIV) coinfection remains an important cause of mortality in antiretroviral therapy (ART) programs. In a cohort of TB-HIV-coinfected patients starting ART, we examined the incidence and predictors of early mortality.
Methods: Consecutive TB-HIV-coinfected patients eligible for ART were enrolled in a cohort study at the Mulago National Tuberculosis and Leprosy Program clinic in Kampala, Uganda. Predictors of mortality were assessed using Cox proportional hazards analysis.
Results: Three hundred and two patients [median CD4 count 53 cells/μL (interquartile range, 20–134)] were enrolled. Fifty-three patients died, 36 (68%) of these died within the first 6 months of TB diagnosis. Male sex [hazard (HR): 2.19; 95% confidence interval (CI): 1.19 to 4.03; P = 0.011], anergy to tuberculin skin test [HR: 2.59 (1.10 to 6.12); P = 0.030], a positive serum cryptococcal antigen result at enrollment (HR: 4.27; 95% CI: 1.50 to 12.13; P = 0.006) and no ART use (HR: 4.63; 95% CI: 2. 37 to 9.03; P < 0.001) were independent predictors of mortality by multivariate analysis. Six (10%) patients with TB immune reconstitution inflammatory syndrome died, and in most, an alternative contributing cause of death was identified.
Conclusions: Mortality among these TB-HIV-coinfected patients was high particularly when presenting with advanced HIV disease and not starting ART, reinforcing the need for timely and joint treatment for both infections. Screening for a concomitant cryptococcal infection and antifungal treatment for patients with cryptococcal antigenemia may further improve clinical outcome.
Tuberculosis (TB) remains a leading cause of morbidity and mortality in HIV-infected patients in sub-Saharan Africa and Asia. The TB epidemic in sub Saharan Africa is fuelled by the HIV epidemic and limited resources for adequate control. Increasing access to antiretroviral therapy (ART) has been associated with improved clinical outcomes in patients with TB-HIV coinfection. This is in contrast to the pre-ART era when dual TB-HIV infection was associated with rapidly progressive disease with poor outcomes. Early mortality however persists in TB-HIV-coinfected patients with advanced HIV disease and comorbid opportunistic infections despite wide availability of ART. The Starting Antiretroviral Therapy at 3 Points in Tuberculosis trial found a 56% reduction in mortality among patients who started ART during TB treatment versus after completion of TB treatment. This further reinforces the notion that ART should not be postponed in patients with HIV-TB coinfection. Recently the CAMbodia Early versus Late Initiation of ART trial demonstrated an improved survival benefit of ART initiation within 2 weeks of TB treatment compared with 8 weeks. Despite WHO guidelines recommending ART start at CD4 counts <350 cells per microliter in pulmonary tuberculosis (PTB) patients and increasing evidence to start ART early, in resource-limited settings, ART initiation in TB-HIV-coinfected patients is often delayed due to limited access to ART. Concerns of drug-drug interaction, drug toxicity, the tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) and adherence to multiple therapeutic regimens remain a hindrance to early commencement of ART. Reported risk factors for mortality in TB-HIV-coinfected patients include the following: low hemoglobin and low CD4 count; low body mass index (BMI) and increased age; gastrointestinal TB and multidrug-resistant TB. In our cohort of TB-HIV-coinfected patients commencing ART, we determined the incidence and predictors of mortality up to 2 years after start of TB treatment and the causes of mortality in patients with TB-IRIS.
Abstract and Introduction
Abstract
Background: Tuberculosis-HIV (TB-HIV) coinfection remains an important cause of mortality in antiretroviral therapy (ART) programs. In a cohort of TB-HIV-coinfected patients starting ART, we examined the incidence and predictors of early mortality.
Methods: Consecutive TB-HIV-coinfected patients eligible for ART were enrolled in a cohort study at the Mulago National Tuberculosis and Leprosy Program clinic in Kampala, Uganda. Predictors of mortality were assessed using Cox proportional hazards analysis.
Results: Three hundred and two patients [median CD4 count 53 cells/μL (interquartile range, 20–134)] were enrolled. Fifty-three patients died, 36 (68%) of these died within the first 6 months of TB diagnosis. Male sex [hazard (HR): 2.19; 95% confidence interval (CI): 1.19 to 4.03; P = 0.011], anergy to tuberculin skin test [HR: 2.59 (1.10 to 6.12); P = 0.030], a positive serum cryptococcal antigen result at enrollment (HR: 4.27; 95% CI: 1.50 to 12.13; P = 0.006) and no ART use (HR: 4.63; 95% CI: 2. 37 to 9.03; P < 0.001) were independent predictors of mortality by multivariate analysis. Six (10%) patients with TB immune reconstitution inflammatory syndrome died, and in most, an alternative contributing cause of death was identified.
Conclusions: Mortality among these TB-HIV-coinfected patients was high particularly when presenting with advanced HIV disease and not starting ART, reinforcing the need for timely and joint treatment for both infections. Screening for a concomitant cryptococcal infection and antifungal treatment for patients with cryptococcal antigenemia may further improve clinical outcome.
Introduction
Tuberculosis (TB) remains a leading cause of morbidity and mortality in HIV-infected patients in sub-Saharan Africa and Asia. The TB epidemic in sub Saharan Africa is fuelled by the HIV epidemic and limited resources for adequate control. Increasing access to antiretroviral therapy (ART) has been associated with improved clinical outcomes in patients with TB-HIV coinfection. This is in contrast to the pre-ART era when dual TB-HIV infection was associated with rapidly progressive disease with poor outcomes. Early mortality however persists in TB-HIV-coinfected patients with advanced HIV disease and comorbid opportunistic infections despite wide availability of ART. The Starting Antiretroviral Therapy at 3 Points in Tuberculosis trial found a 56% reduction in mortality among patients who started ART during TB treatment versus after completion of TB treatment. This further reinforces the notion that ART should not be postponed in patients with HIV-TB coinfection. Recently the CAMbodia Early versus Late Initiation of ART trial demonstrated an improved survival benefit of ART initiation within 2 weeks of TB treatment compared with 8 weeks. Despite WHO guidelines recommending ART start at CD4 counts <350 cells per microliter in pulmonary tuberculosis (PTB) patients and increasing evidence to start ART early, in resource-limited settings, ART initiation in TB-HIV-coinfected patients is often delayed due to limited access to ART. Concerns of drug-drug interaction, drug toxicity, the tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) and adherence to multiple therapeutic regimens remain a hindrance to early commencement of ART. Reported risk factors for mortality in TB-HIV-coinfected patients include the following: low hemoglobin and low CD4 count; low body mass index (BMI) and increased age; gastrointestinal TB and multidrug-resistant TB. In our cohort of TB-HIV-coinfected patients commencing ART, we determined the incidence and predictors of mortality up to 2 years after start of TB treatment and the causes of mortality in patients with TB-IRIS.