Prevalent and Incident Tuberculosis Are Independent Risk Factors for Mortality among Patients Accessing Antiretroviral Therapy in South Africa (original) (raw)
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International Journal of Infectious Diseases, 2017
Nine out of ten tuberculosis deaths occur in tuberculosis-burdened countries, particularly Sub Saharan Africa. In these setting mortality has not been fully described. We describe the magnitude and pattern of TB mortality in Tanzania. METHODS: A multicenter prospective cohort study was conducted among HIV infected and uninfected pulmonary tuberculosis patients from time of anti-TB treatment initiation to completion. Patients were censored at the time of treatment completion, or at their last visit for those who did not complete TB treatment. Kaplan-Meier curves were used to estimate time to death; cox proportional hazards model was used to examine risk factors for mortality. RESULTS: A total of 58 deaths out of 1696 patients (3.4%) occurred, two thirds (n = 39) during the first two months of treatment. Compared to HIV un-infected TB patients, mortality risk for TB/HIV co-infected patients was least when antiretroviral therapy (ART) was initiated after 14 days of anti-TB (RR = 3.55; 95% CI: 1.44, 8.73 p < 0.0001) and highest when ART was initiated 90 days or less prior to anti-TB and within the first 14 days of anti-TB therapy (RR = 10; 95% CI: 3.28, 30.54; p < 0.0001). CONCLUSION: Meticulously planned and supervised antiretroviral therapy reduces mortality among TB/ HIV patients. Among patients with TB/HIV naïve of ART, withholding ART until the third week of antituberculosis therapy will likely reduce TB mortality in Tanzania. Patients on ART and later develop tuberculosis should be closely monitored.
Objective: To quantify the impact of tuberculosis (TB) co-infection on death and loss to follow-up (LTFU) 12 months after entry into an ART program. Design: Prospective intervention study. Methods: From May 2007 to 2008, patients undergoing pre-ART training in Durban, South Africa, were screened for pulmonary TB using mycobacterial culture. Subjects missing appointments for .3 months were phoned. Patients who could not be reached were considered LTFU. Deaths were ascertained by report from family members. We used the Kaplan–Meier method to estimate time to LTFU or death for 3 groups at enrollment as follows: (1) newly diagnosed with TB by sputum culture; (2) on TB treatment (ie, previously diagnosed); and (3) TB free. We evaluated the role of TB on mortality and LTFU using Cox proportional hazards models. Results: Nine hundred fifty-one HIV-infected subjects were enrolled; 59% were female, and median baseline CD4 count was 90 cells per microliter (IQR: 41–148 cells/mL). One hundred forty-four (15%) were newly diagnosed with TB by sputum culture; an additional 199 (21%) were already on TB treatment. By 12 months, 26% newly diagnosed with TB at enrollment died or were LTFU, compared with 19% already on TB treatment, and 14% who were TB free (P = 0.001). Controlling for age, sex, smoking, CD4, and opportunistic infection history, subjects newly diagnosed with pulmonary TB were 76% more likely to die or be LTFU (hazard ratio: 1.76, 95% confidence interval: 1.20 to 2.60) than those without TB. Conclusions: HIV/TB co-infected individuals are more likely to die or be LTFU within 12 months of ART clinic entry in South Africa. These patients require intensive follow-up during ART initiation.
Background. In 2013, the tuberculosis (TB) mortality rate was highest in southern Zimbabwe at 16%. We therefore sought to determine factors associated with mortality among registered TB patients in this region. Methodology. This was a retrospective record review of registered patients receiving anti-TB treatment in 2013. Results. Of 1,971 registered TB patients, 1,653 (84%) were new cases compared with 314 (16%) retreatment cases. There were 1,538 (78%) TB/human immunodeficiency virus (HIV) coinfected patients, of whom 1,399 (91%) were on antiretroviral therapy (ART) with median pre-ART CD4 count of 133 cells/uL (IQR, 46–282). Overall, 428 (22%) TB patients died. Factors associated with increased mortality included being ≥65 years old [adjusted relative risk (ARR) = 2.48 (95% CI 1.35–4.55)], a retreatment TB case [ARR = 1.34 (95% CI, 1.10–1.63)], and being HIV-positive [ARR = 1.87 (95% CI, 1.44–2.42)] whilst ART initiation was protective [ARR = 0.25 (95% CI, 0.22–0.29)]. Cumulative mortality rates were 10%, 14%, and 21% at one, two, and six months, respectively, after starting TB treatment. Conclusion. There was high mortality especially in the first two months of anti-TB treatment, with risk factors being recurrent TB and being HIV-infected, despite a high uptake of ART.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2014
Objective: To identify determinants of tuberculosis (TB) case fatality including the impact of antiretroviral therapy (ART) at different CD4 thresholds for HIV-positive adult and adolescent TB patients. Methods: Through a retrospective analysis of the electronic TB database, we identified the HIV status of newly registered patients aged $15 years. Multivariable Cox proportional hazard models were used to determine the risk factors for TB case fatality in these patients.
International Journal of HIV/AIDS Prevention, Education and Behavioural Science, 2019
Introduction: The use of antiretroviral therapy (ART) has dramatically decreased HIV-associated morbidity and mortality in high-and low-income countries with a corresponding reduction in tuberculosis (TB) incidence. Nevertheless, the risk of TB remains substantially higher in people living with HIV (PLHIV) compared to non-HIV infected individuals. In Cameroon, free ART was introduced in 2007 and our understanding of the possible role of ART in reducing HIV-associated TB remains limited. We assessed TB incidence, mortality and risk factors for TB and mortality among PLHIV treated at Buea Regional Hospital between 2008 and 2014. Materials and Methods: In a retrospective study we reviewed the records of 1,477 HIV patients on ART. The data was entered and analysed using SPSS version 21. Bivariate and Multivariate logistic regression analysis were used to determine the risk factors associated with TB and mortality occurrences at 5% significance level. Results: Of the 1477 patients' records that was reviewed, females (70.7%) constituted a greater proportion. Majority of the participants (60.5%) were between the ages 21-40 years (mean: 37.5 ± 11.5. SD). A total of 209 patients developed TB giving an overall TB incidence density rate 4.25/100PYR (95% CI: 2.47-6.46). There was an increasing trend in the incidence of TB over the years from 1.69 (95% CI: 0.72-1.98) in 2008 to 19.63 (95% CI: 7.36-21.20) in 2014. The overall mortality rate was 12.4% (183/1477) of which 38.8% (71/183) of them were on TB treatment or previously treated for TB. In a multivariate analysis, low CD4 cells level at ART initiation (AOR: 1.3, 95% CI: 1.11-.2.10), WHO HIV clinical stage 3 and 4 (AOR: 1.52, 95% CI: 1.01-2.22) were significantly associated with increase odds of TB occurrence. Conclusion: Even in the era of HAART, TB still remains a significant cause of mortality among PLHIV and therefore efforts should be scaled-up for early diagnosis and prompt treatment of TB.
AIDS, 2012
Westreich and colleagues reported on the association between treatment for pulmonary tuberculosis (TB) at baseline in a South African antiretroviral treatment (ART) programme and subsequent mortality risk [1,2]. Although patients receiving TB treatment had higher all-cause mortality risk compared to those not treated, no such association was observed after adjustment for baseline CD4 count, other patient variables and loss to follow-up (hazard ratio,1.06; 95%CI 0.75-1.49) [2]. This finding was robust when additional death registry data were included and follow-up was extended by 18 months [1].
Transactions of the Royal Society of Tropical Medicine and Hygiene, 2012
Preceding studies on morbidities and mortalities associated with TB in a cohort of HIV care indicate high incidence of TB development and premature death among patients on highly active antiretroviral treatment (HAART). This study aims to measure the rate of TB, TB mortality, and associated risk factors following commencement of HAART in a cohort of patients attending HIV care in Ethiopia. Patient information was gathered from the hospital register and analysed. TB incidence peaked within six months of HAART initiation, and dropped from 3.3/100 person-years in the first year to 0.4/100 person-years in the fifth year. At baseline, risk factors associated with TB included WHO clinical stage 3 HIV infection (adjusted hazard ratio (AHR) 2.53; 95% CI 1.70-3.70), WHO clinical stage 4 HIV infection (AHR, 3.86; 95% CI 2.54-5.86), and patients who were bed ridden >50% a day (AHR, 1.52; 95% CI 1.13-2.05). The rate of mortality was 6.9% (incidence 2.8 per 100 person-years) and 57% of deaths occurred in the first six months of HAART initiation. Multivariate Cox model indicated WHO clinical stage 4 HIV infection, CD4+ cell count <50 cells/l, bed ridden >50% a day, and TB after HAART initiation as baseline independent predictors of mortality. Additional evidence shows that regular CD4+monitoring of patients before HAART initiation as well as earlier HAART initiation decreases death, and regular clinical staging decreases TB incidence.
BMC Infectious Diseases, 2019
Background: Empirical treatment of tuberculosis (TB) may be necessary in patients with negative or no Xpert MTB/RIF results. In a context with access to Xpert, we assessed mortality in the 6 months after the initial TB consultation among HIV-positive and HIV-negative patients who received empirical TB treatment or TB treatment based on bacteriological confirmation and we compared it with the mortality among those who did not receive TB treatment. Methods: This prospective cohort study included consecutively adult patients with signs and symptoms of TB attending an outpatient TB clinic in Western Kenya. At the first consultation, patients received a clinical exam and chest X-ray. Sputum was collected for microscopy, Xpert and Mycobacterium tuberculosis complex (MTB) culture. Patients not started on TB treatment were reassessed after 5 days. All patients bacteriologically confirmed (positive Xpert or culture) received TB treatment. Empirical treatment was defined as a decision to start TB treatment without bacteriological confirmation. Patients were reassessed after 6 months. Results: Of 606 patients included, 344/606 (56.8%) were women. Median age was 35 years [Interquartile Range (IQR): 27-47] and 398/594 (67.0%) were HIV-positive. In total, 196/606 (32.3%) patients were Xpert-or culture-positive and 331/606 (54.6%) started TB treatment. Overall, 100/398 (25.1%) HIV-positive and 31/196 (15.8%) HIV-negative patients received empirical treatment. Mortality in the 6 months following the first consultation was 1.6 and 0.8/100 patientmonths among HIV-positive and HIV-negative patients respectively. In the multivariate analyses, TB treatment-whether empirical or based on bacteriological confirmation-was not associated with increased mortality among HIV-positive patients (aHR:2.51, 95%CI:0.79-7.90 and aHR:1.25, 95%CI:0.37-4.21 respectively). However, HIV-negative patients who received empirical treatment had a higher risk of mortality (aHR:4.85, 95%CI:1.08-21.67) compared to those not started on treatment. HIV-negative patients treated for TB based on bacteriological confirmation did not have a different risk of mortality (aHR:0.77, 95%CI:0.08-7.41). Conclusions: Our findings suggest that in a context with access to Xpert, clinicians should continue using empirical TB treatment in HIV-positive patients with signs and symptoms of TB and negative Xpert results. However, differential diagnoses other than TB should be actively sought before initiating empirical TB treatment, particularly in HIV-negative patients.