High mortality among patients hospitalized for drug-resistant tuberculosis with acquired second-line drug resistance and high HIV prevalence
© 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association..
OBJECTIVES: We compared mortality between HIV-positive and HIV-negative South African adults with drug-resistant tuberculosis (DR-TB) and high incidence of acquired second-line drug resistance.
METHODS: We performed a retrospective review of DR-TB patients with serial second-line TB drug susceptibility tests (2008-2015) who were hospitalized at a specialized TB hospital. We used Kaplan-Meier analysis and Cox models to examine associations with mortality.
RESULTS: Of 245 patients, the median age was 33 years, 54% were male and 40% were HIV-positive, 96% of whom had ever received antiretroviral therapy (ART). At initial drug resistance detection, 99% of patients had resistance to at least rifampicin and isoniazid, and 18% had second-line drug resistance (fluoroquinolones and/or injectable drugs). At later testing, 88% of patients had acquired additional second-line drug resistance. Patient-initiated treatment interruptions (> 2 months) occurred in 47%. Mortality was 79%. Those with HIV had a shorter time to death (p = 0.02; log-rank): median survival time from DR-TB treatment initiation was 2.44 years [95% confidence interval (CI): 2.09-3.15] versus 3.99 years (95% CI: 3.12-4.75) for HIV-negative patients. HIV-positive patients who received ART within 6 months before DR-TB treatment had a higher mortality hazard than HIV-negative patients [adjusted hazard ratio (aHR) ratio = 1.82, 95% CI: 1.21-2.74]. By contrast, HIV-positive patients who did not receive ART within 6 months before DR-TB treatment did not have a significantly higher mortality hazard than HIV-negative patients (aHR = 1.09; 95% CI: 0.72-1.65), although those on ART had lower median CD4 counts than those not on ART (157 vs. 281 cells/μL, respectively; p = 0.02).
CONCLUSIONS: A very high incidence of acquired second-line drug resistance and high overall mortality were observed, reinforcing the need to reduce the risk of acquired resistance and for more effective treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
HIV medicine - 23(2022), 10 vom: 08. Nov., Seite 1085-1097 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Anderson, Kim [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.10.2022 Date Revised 06.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/hiv.13318 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM341304905 |
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| 245 | 1 | 0 | |a High mortality among patients hospitalized for drug-resistant tuberculosis with acquired second-line drug resistance and high HIV prevalence |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 14.10.2022 | ||
| 500 | |a Date Revised 06.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association. | ||
| 520 | |a OBJECTIVES: We compared mortality between HIV-positive and HIV-negative South African adults with drug-resistant tuberculosis (DR-TB) and high incidence of acquired second-line drug resistance | ||
| 520 | |a METHODS: We performed a retrospective review of DR-TB patients with serial second-line TB drug susceptibility tests (2008-2015) who were hospitalized at a specialized TB hospital. We used Kaplan-Meier analysis and Cox models to examine associations with mortality | ||
| 520 | |a RESULTS: Of 245 patients, the median age was 33 years, 54% were male and 40% were HIV-positive, 96% of whom had ever received antiretroviral therapy (ART). At initial drug resistance detection, 99% of patients had resistance to at least rifampicin and isoniazid, and 18% had second-line drug resistance (fluoroquinolones and/or injectable drugs). At later testing, 88% of patients had acquired additional second-line drug resistance. Patient-initiated treatment interruptions (> 2 months) occurred in 47%. Mortality was 79%. Those with HIV had a shorter time to death (p = 0.02; log-rank): median survival time from DR-TB treatment initiation was 2.44 years [95% confidence interval (CI): 2.09-3.15] versus 3.99 years (95% CI: 3.12-4.75) for HIV-negative patients. HIV-positive patients who received ART within 6 months before DR-TB treatment had a higher mortality hazard than HIV-negative patients [adjusted hazard ratio (aHR) ratio = 1.82, 95% CI: 1.21-2.74]. By contrast, HIV-positive patients who did not receive ART within 6 months before DR-TB treatment did not have a significantly higher mortality hazard than HIV-negative patients (aHR = 1.09; 95% CI: 0.72-1.65), although those on ART had lower median CD4 counts than those not on ART (157 vs. 281 cells/μL, respectively; p = 0.02) | ||
| 520 | |a CONCLUSIONS: A very high incidence of acquired second-line drug resistance and high overall mortality were observed, reinforcing the need to reduce the risk of acquired resistance and for more effective treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
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| 650 | 4 | |a drug-resistant tuberculosis | |
| 650 | 4 | |a mortality | |
| 650 | 7 | |a Antitubercular Agents |2 NLM | |
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| 700 | 1 | |a Pietersen, Elize |e verfasserin |4 aut | |
| 700 | 1 | |a Shepherd, Bryan E |e verfasserin |4 aut | |
| 700 | 1 | |a Bian, Aihua |e verfasserin |4 aut | |
| 700 | 1 | |a Dheda, Keertan |e verfasserin |4 aut | |
| 700 | 1 | |a Warren, Robin |e verfasserin |4 aut | |
| 700 | 1 | |a Sterling, Timothy R |e verfasserin |4 aut | |
| 700 | 1 | |a van der Heijden, Yuri F |e verfasserin |4 aut | |
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