Severe adverse events during second-line tuberculosis treatment in the context of high HIV Co-infection in South Africa: a retrospective cohort study Public Deposited

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  • Sinanovic, Edina
    • Other Affiliation: Health Economics Unit, School of Family and Public Health, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
  • Schnippel, Kathryn
    • Other Affiliation: Right to Care, Johannesburg, South Africa; Clinical HIV Research Unit, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Health Economics Unit, School of Family and Public Health, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
  • Maitisa, Norah
    • Other Affiliation: Wits Reproductive Health and HIV Research Institute, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; GlaxoSmithKline, Bryanston, South Africa
  • Evans, Denise
    • Other Affiliation: Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa
  • Berhanu, Rebecca H
    • Affiliation: School of Medicine
    • Other Affiliation: Right to Care, Johannesburg, South Africa; Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa
  • Firnhaber, Cynthia
    • Other Affiliation: Right to Care, Johannesburg, South Africa; Clinical HIV Research Unit, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
  • Black, Andrew
    • Other Affiliation: Wits Reproductive Health and HIV Research Institute, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
Abstract
  • Abstract Background According to the World Health Organization, South Africa ranks as one of the highest burden of TB, TB/HIV co-infection, and drug-resistant TB (DR-TB) countries. DR-TB treatment is complicated to administer and relies on the use of multiple toxic drugs, with potential for severe adverse drug reactions. We report the occurrence of adverse events (AEs) during a standardised DR-TB treatment regimen at two outpatient, decentralized, public-sector sites in Johannesburg, South Africa. Methods We reviewed medical records of the six-month intensive treatment phase for rifampicin-resistant (RR) TB patients registered May 2012 - December 2014. Patients contributed follow-up time until death, loss from treatment, censoring (6 months) or data extraction. A standardized regimen of kanamycin, moxifloxacin, ethionamide, terizidone, and pyrazinamide was used according to national guidelines. AEs were graded using the AIDS Clinical Trial Group scale. We present subhazard ratios from competing risk analysis for time to severe AE, accounting for mortality and loss from treatment. Results Across the two sites, 578 eligible patient files were reviewed. 36.7 % were categorized as low weight (≤50 kg) at DR-TB initiation. 76.0 % had no history of TB treatment prior to the current episode of RR TB. 26.8 % were diagnosed with RR TB while hospitalized, indicating poor clinical condition. 82.5 % of patients were also HIV positive, of whom 43.8 % were on ART prior to RR TB treatment and 32.1 % initiated ART with or after RR TB treatment. Median CD4 count was 114.5 (IQR: 45-246.5). Overall, 578 reports of AEs were captured for 204 patients (35.3 %) and 110 patients (19.0 %) had at least one severe AE reported. Patients with at least one AE experienced a median of 3 (IQR: 2-4) AEs per patient. HIV-positive patients with CD4 counts ≤100 cells/mm3 and those newly initiating ART were more likely to experience a severe AE (sHR: 2.76, 95 % CI: 1.30–5.84 and sHR: 3.07, 95 % CI: 1.46–6.46, respectively). Conclusion Severe AE are common during the first 6 months of RR TB treatment and HIV-positive patients newly initiating ART have the highest subdistribution hazard ratio for severe AE, accounting for the competing risks of death and loss from treatment.
Date of publication
Identifier
  • doi:10.1186/s12879-016-1933-0
Resource type
  • Article
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  • In Copyright
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  • The Author(s).
Language
  • English
Bibliographic citation
  • BMC Infectious Diseases. 2016 Oct 21;16(1):593
Publisher
  • BioMed Central
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