Giuseppe
Emeritus
[Source: PLoS ONE, full text: (LINK). Abstract, edited.]
Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) among a Cohort of South African Patients with High HIV Prevalence
by Jason E. Farley, Malathi Ram, William Pan, Stacie Waldman, Gail H. Cassell, Richard E. Chaisson, Karin Weyer, Joey Lancaster, Martie Van der Walt
Background
Multidrug-resistant tuberculosis (MDR-TB) is a major clinical challenge, particularly in patients with human immunodeficiency virus (HIV) co-infection. MDR-TB treatment is increasingly available, but outcomes have not been well characterized. South Africa has provided MDR-TB treatment for a decade, and we evaluated outcomes by HIV status for patients enrolled between 2000 and 2004 prior to anti-retroviral access.
Methods
We assessed treatment outcomes in a prospective cohort of patients with MDR-TB from eight provincial programs providing second line drugs. World Health Organization definitions were used. Results were stratified by HIV status.
Results
Seven hundred fifty seven patients with known HIV status were included in the final analysis, and HIV infection was documented in 287 (38%). Overall, 348 patients (46.0%) were successfully treated, 74 (9.8%) failed therapy, 177 (23.4%) died and 158 (20.9%) defaulted. Patients with HIV were slightly younger and less likely to be male compared to HIV negative patients. Patients with HIV were less likely to have a successful treatment outcome (40.0 vs. 49.6; P<0.05) and more likely to die (35.2 vs. 16.2; P<0.0001). In a competing risk survival analysis, patients with HIV had a higher hazard of death (HR: 2.33, P<0.0001). Low baseline weight (less than 45 kg and less than 60 kg) was also associated with a higher hazard of death (HR: 2.52, P<0.0001; and HR: 1.50, P<0.0001, respectively, compared to weight greater than 60 kg). Weight less than 45 kg had higher risk of failure (HR: 3.58, P<0.01). Any change in treatment regimen was associated with a higher hazard of default (HR: 2.86; 95% CI 1.55?5.29, P<0.001) and a lower hazard of death (HR: 0.63, P<0.05).
Conclusions
In this MDR-TB treatment program patients with HIV infection and low weight had higher hazards of death. Overall treatment outcomes were poor. Efforts to improve treatment for MDR-TB are urgently needed.
Citation: Farley JE, Ram M, Pan W, Waldman S, Cassell GH, et al. (2011) Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) among a Cohort of South African Patients with High HIV Prevalence. PLoS ONE 6(7): e20436. doi:10.1371/journal.pone.0020436
Editor: Delia Goletti, National Institute for Infectious Diseases (L. Spallanzani), Italy
Received: February 25, 2011; Accepted: April 20, 2011; Published: July 22, 2011
Copyright: ? 2011 Farley et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was sponsored by a grant from the Burroughs Wellcome Fund to the Johns Hopkins University School of Nursing. This study was also partially supported by the Fogarty International Center at the National Institutes of Health by grant number 5R25TW007506. No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: Dr. Cassell and Ms. Waldman were previously employed by Eli Lily, Inc. at the time of the funding and data collection. Neither at the time of submission and for the proceeding 6 months were the authors employed with Eli Lily or any other commercial company. Dr. Cassell is an advisory board member of the Johns Hopkins University School of Nursing and Board Member to Burroughs Wellcome. As a mentor to both Dr. Farley and Ms. Waldman during this time she facilitated securing this grant from BW to assist in their participation/conduct of this study. At no time was she compensated by Eli Lily for this study, influenced by the company to alter study aims, nor was she required to report any data on this study to Eli Lily, Inc. Although Ms. Waldman was employed with Eli Lily at the time of data collection, she took personal vacation to conduct study related duties. This experience was part of her MPH capstone project at the Bloomberg School of Public Health. At no time was she compensated, influenced or required to report any data on this study to Eli Lily, Inc. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.
* E-mail: jfarley@son.jhmi.edu
- -------by Jason E. Farley, Malathi Ram, William Pan, Stacie Waldman, Gail H. Cassell, Richard E. Chaisson, Karin Weyer, Joey Lancaster, Martie Van der Walt
Background
Multidrug-resistant tuberculosis (MDR-TB) is a major clinical challenge, particularly in patients with human immunodeficiency virus (HIV) co-infection. MDR-TB treatment is increasingly available, but outcomes have not been well characterized. South Africa has provided MDR-TB treatment for a decade, and we evaluated outcomes by HIV status for patients enrolled between 2000 and 2004 prior to anti-retroviral access.
Methods
We assessed treatment outcomes in a prospective cohort of patients with MDR-TB from eight provincial programs providing second line drugs. World Health Organization definitions were used. Results were stratified by HIV status.
Results
Seven hundred fifty seven patients with known HIV status were included in the final analysis, and HIV infection was documented in 287 (38%). Overall, 348 patients (46.0%) were successfully treated, 74 (9.8%) failed therapy, 177 (23.4%) died and 158 (20.9%) defaulted. Patients with HIV were slightly younger and less likely to be male compared to HIV negative patients. Patients with HIV were less likely to have a successful treatment outcome (40.0 vs. 49.6; P<0.05) and more likely to die (35.2 vs. 16.2; P<0.0001). In a competing risk survival analysis, patients with HIV had a higher hazard of death (HR: 2.33, P<0.0001). Low baseline weight (less than 45 kg and less than 60 kg) was also associated with a higher hazard of death (HR: 2.52, P<0.0001; and HR: 1.50, P<0.0001, respectively, compared to weight greater than 60 kg). Weight less than 45 kg had higher risk of failure (HR: 3.58, P<0.01). Any change in treatment regimen was associated with a higher hazard of default (HR: 2.86; 95% CI 1.55?5.29, P<0.001) and a lower hazard of death (HR: 0.63, P<0.05).
Conclusions
In this MDR-TB treatment program patients with HIV infection and low weight had higher hazards of death. Overall treatment outcomes were poor. Efforts to improve treatment for MDR-TB are urgently needed.
Citation: Farley JE, Ram M, Pan W, Waldman S, Cassell GH, et al. (2011) Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) among a Cohort of South African Patients with High HIV Prevalence. PLoS ONE 6(7): e20436. doi:10.1371/journal.pone.0020436
Editor: Delia Goletti, National Institute for Infectious Diseases (L. Spallanzani), Italy
Received: February 25, 2011; Accepted: April 20, 2011; Published: July 22, 2011
Copyright: ? 2011 Farley et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was sponsored by a grant from the Burroughs Wellcome Fund to the Johns Hopkins University School of Nursing. This study was also partially supported by the Fogarty International Center at the National Institutes of Health by grant number 5R25TW007506. No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: Dr. Cassell and Ms. Waldman were previously employed by Eli Lily, Inc. at the time of the funding and data collection. Neither at the time of submission and for the proceeding 6 months were the authors employed with Eli Lily or any other commercial company. Dr. Cassell is an advisory board member of the Johns Hopkins University School of Nursing and Board Member to Burroughs Wellcome. As a mentor to both Dr. Farley and Ms. Waldman during this time she facilitated securing this grant from BW to assist in their participation/conduct of this study. At no time was she compensated by Eli Lily for this study, influenced by the company to alter study aims, nor was she required to report any data on this study to Eli Lily, Inc. Although Ms. Waldman was employed with Eli Lily at the time of data collection, she took personal vacation to conduct study related duties. This experience was part of her MPH capstone project at the Bloomberg School of Public Health. At no time was she compensated, influenced or required to report any data on this study to Eli Lily, Inc. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.
* E-mail: jfarley@son.jhmi.edu