Independent Predictors of Tuberculosis Mortality in a High HIV Prevalence Setting

Background

Identifying those at increased risk of death during TB treatment is a priority in resource-constrained settings. We performed this study to determine predictors of mortality during TB treatment.

Methods

We performed a retrospective analysis of a TB surveillance population in a high HIV prevalence area that was recorded in ETR.net (Electronic Tuberculosis Register). Adult TB cases initiated TB treatment from 2007 through 2009 in Khayelitsha, South Africa. Cox proportional hazards models were used to identify risk factors for death (after multiple imputations for missing data). Model selection was performed using Akaike’s Information Criterion to obtain the most relevant predictors of death.

Results

Of 16,209 adult TB cases, 851 (5.3 %) died during TB treatment. In all TB cases, advancing age, co-infection with HIV, a prior history of TB and the presence of both pulmonary and extra-pulmonary TB were independently associated with an increasing hazard of death. In HIV-infected TB cases, advancing age and female gender were independently associated with an increasing hazard of death. Increasing CD4 counts and antiretroviral treatment during TB treatment were protective against death. In HIV-uninfected TB cases, advancing age was independently associated with death, whereas smear-positive disease was protective.

Conclusion

We identified several independent predictors of death during TB treatment in resource-constrained settings. Our findings inform resource-constrained settings about certain subgroups of TB patients that should be targeted to improve mortality during TB treatment.

Below: Kaplan Meier plot showing cumulative mortality during TB treatment: (1) overall mortality, and (2) mortality by HIV status

Full article at:  http://goo.gl/sfSKwA

By:  Dominique J. Pepper,  Michael Schomaker, Robert J. Wilkinson, Virginia de Azevedo and Gary Maartens

Department of Medicine, University of Cape Town

Critical Care Medicine Department, National Institutes of Health

More at:  https://twitter.com/hiv_insight

And: http://twitter.com/Prison_Health

Time to ART Initiation among Patients Treated for Rifampicin-Resistant Tuberculosis in Khayelitsha, South Africa: Impact on Mortality and Treatment Success

Khayelitsha, South Africa, with high burdens of rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection.

To describe time to antiretroviral treatment (ART) initiation among HIV-infected RR-TB patients initiating RR-TB treatment and to assess the association between time to ART initiation and treatment outcomes.

A retrospective cohort study of patients with RR-TB and HIV co-infection not on ART at RR-TB treatment initiation.

Of the 696 RR-TB and HIV-infected patients initiated on RR-TB treatment between 2009 and 2013, 303 (44%) were not on ART when RR-TB treatment was initiated. The median CD4 cell count was 126 cells/mm³. Overall 257 (85%) patients started ART during RR-TB treatment, 33 (11%) within 2 weeks, 152 (50%) between 2–8 weeks and 72 (24%) after 8 weeks. Of the 46 (15%) who never started ART, 10 (21%) died or stopped RR-TB treatment within 4 weeks and 16 (37%) had at least 4 months of RR-TB treatment. Treatment success and mortality during treatment did not vary by time to ART initiation: treatment success was 41%, 43%, and 50% among patients who started ART within 2 weeks, between 2–8 weeks, and after 8 weeks (p = 0.62), while mortality was 21%, 13% and 15% respectively (p = 0.57). Mortality was associated with never receiving ART (adjusted hazard ratio (aHR) 6.0, CI 2.1–18.1), CD4 count ≤100 (aHR 2.1, CI 1.0–4.5), and multidrug-resistant tuberculosis (MDR-TB) with second-line resistance (aHR 2.5, CI 1.1–5.4).

Despite wide variation in time to ART initiation among RR-TB patients, no differences in mortality or treatment success were observed. However, a significant proportion of patients did not initiate ART despite receiving >4 months of RR-TB treatment. Programmatic priorities should focus on ensuring all patients with RR-TB/HIV co-infection initiate ART regardless of CD4 count, with special attention for patients with CD4 counts ≤ 100 to initiate ART as soon as possible after RR-TB treatment initiation.

Below:  Kaplan-Meier plot of time to antiretroviral treatment initiation for HIV infected rifampicin resistant tuberculosis patients

Below:  Kaplan-Meier plot of survival during treatment of rifampicin resistant tuberculosis by ART initiation, from multivariate Cox regression analysis for HIV co-infected patients

Full article at:  http://goo.gl/NjegI5

By: 

Johnny Flippie Daniels, Erika Mohr, Vivian Cox, Sizulu Moyo, Jennifer Hughes, Gilles van Cutsem

Médecins sans Frontières, Khayelitsha, Cape Town, South Africa

Mohammed Khogali

Médecins sans Frontières, Luxembourg, Luxembourg

Sizulu Moyo

Human Sciences Research Council, HIV/AIDS, STIs and TB programme, Cape Town, South Africa

Mary Edginton

International Union against TB and Lung Disease, Paris, France

Mary Edginton

School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Sven Gudmund Hinderaker

University of Bergen, Bergen, Norway

Graeme Meintjes

Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa

Virginia De Azevedo

City of Cape Town Department of Health, Cape Town, South Africa

Gilles van Cutsem

Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa

Helen Suzanne Cox

Division of Medical Microbiology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa

 

More at:  https://twitter.com/hiv_insight

And: http://twitter.com/Prison_Health

Independent Predictors of Tuberculosis Mortality in a High HIV Prevalence Setting: A Retrospective Cohort Study

Identifying those at increased risk of death during TB treatment is a priority in resource-constrained settings. We performed this study to determine predictors of mortality during TB treatment.

We performed a retrospective analysis of a TB surveillance population in a high HIV prevalence area that was recorded in ETR.net (Electronic Tuberculosis Register). Adult TB cases initiated TB treatment from 2007 through 2009 in Khayelitsha, South Africa. Cox proportional hazards models were used to identify risk factors for death (after multiple imputations for missing data). Model selection was performed using Akaike’s Information Criterion to obtain the most relevant predictors of death.

Of 16,209 adult TB cases, 851 (5.3 %) died during TB treatment. In all TB cases, advancing age, co-infection with HIV, a prior history of TB and the presence of both pulmonary and extra-pulmonary TB were independently associated with an increasing hazard of death. In HIV-infected TB cases, advancing age and female gender were independently associated with an increasing hazard of death. Increasing CD4 counts and antiretroviral treatment during TB treatment were protective against death. In HIV-uninfected TB cases, advancing age was independently associated with death, whereas smear-positive disease was protective.

We identified several independent predictors of death during TB treatment in resource-constrained settings. Our findings inform resource-constrained settings about certain subgroups of TB patients that should be targeted to improve mortality during TB treatment.

Below:  Kaplan Meier plot showing cumulative mortality during TB treatment: (1) overall mortality, and (2) mortality by HIV status

Full article at: http://goo.gl/tt4txn

By: Dominique J. Pepper¹², Michael Schomaker³, Robert J. Wilkinson¹⁴⁵, Virginia de Azevedo⁶ and Gary Maartens^17*

¹Department of Medicine, University of Cape Town, Anzio Road, Cape Town 7925, South Africa

²Critical Care Medicine Department, National Institutes of Health, 10 Center Drive, Bethesda, USA

³Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Anzio Road, Cape Town 7925, South Africa

⁴Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa

⁵Department of Medicine, Imperial College, London W2 1PG, UK

⁶City Health, Cape Town, South Africa

⁷Division of Pharmacology, Groote Schuur Hospital, Anzio Road, Cape Town 7925, South Africa

  

More at:  https://twitter.com/hiv_insight