Toxicity related to standard TB therapy for pulmonary tuberculosis and treatment outcomes in the REMoxTB study according to HIV status

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dc.contributor.authorTweed, Conor D
dc.contributor.authorCrook, Angela M
dc.contributor.authorDawson, Rodney
dc.contributor.authorDiacon, Andreas H
dc.contributor.authorMcHugh, Timothy D
dc.contributor.authorMendel, Carl M
dc.contributor.authorMeredith, Sarah K
dc.contributor.authorMohapi, Lerato
dc.contributor.authorMurphy, Michael E
dc.contributor.authorNunn, Andrew J
dc.contributor.authorPhillips, Patrick P J
dc.contributor.authorSingh, Kasha P
dc.contributor.authorSpigelman, Melvin
dc.contributor.authorGillespie, Stephen H
dc.date.accessioned2019-12-10T09:12:53Z
dc.date.available2019-12-10T09:12:53Z
dc.date.issued2019-08-14
dc.date.updated2019-08-18T03:25:39Z
dc.description.abstractAbstract Background The phase III REMoxTB study prospectively enrolled HIV-positive (with CD4+ count > 250 cells, not on anti-retroviral therapy) and HIV-negative patients. We investigated the incidence of adverse events and cure rates according to HIV status for patients receiving standard TB therapy in the trial. Methods Forty-two HIV-positive cases were matched to 220 HIV-negative controls by age, gender, ethnicity, and trial site using coarsened exact matching. Grade 3 and 4 adverse events (AEs) were summarised by MedDRA System Organ Class. Kaplan-Meier curves for time to first grade 3 or 4 AE were constructed according to HIV status with hazard ratios calculated. Patients were considered cured if they were culture negative 18 months after commencing therapy with ≥2 consecutive negative culture results. Results Twenty of 42 (47.6%) HIV-positive and 34 of 220 (15.5%) HIV-negative patients experienced ≥1 grade 3 or 4 AE, respectively. The majority of these were hepatobiliary disorders that accounted for 12 of 40 (30.0%) events occurring in 6 of 42 (14.3%) HIV-positive patients and for 15 of 60 (25.0%) events occurring in 9 of 220 (4.1%) HIV-negative patients. The median time to first grade 3 or 4 AE was 54 days (IQR 15.5–59.0) for HIV-positive and 29.5 days (IQR 9.0–119.0) for HIV-negative patients, respectively. The hazard ratio for experiencing a grade 3 or 4 AE among HIV-positive patients was 3.25 (95% CI 1.87–5.66, p < 0.01). Cure rates were similar, with 38 of 42 (90.5%) HIV-positive and 195 of 220 (88.6%) HIV-negative patients (p = 0.73) cured at 18 months. Conclusions HIV-positive patients receiving standard TB therapy in the REMoxTB study were at greater risk of adverse events during treatment but cure rates were similar when compared to a matched sample of HIV-negative patients.
dc.identifier.apacitationTweed, C. D., Crook, A. M., Dawson, R., Diacon, A. H., McHugh, T. D., Mendel, C. M., ... Gillespie, S. H. (2019). Toxicity related to standard TB therapy for pulmonary tuberculosis and treatment outcomes in the REMoxTB study according to HIV status. http://hdl.handle.net/11427/30692en_ZA
dc.identifier.chicagocitationTweed, Conor D, Angela M Crook, Rodney Dawson, Andreas H Diacon, Timothy D McHugh, Carl M Mendel, Sarah K Meredith, et al "Toxicity related to standard TB therapy for pulmonary tuberculosis and treatment outcomes in the REMoxTB study according to HIV status." (2019) http://hdl.handle.net/11427/30692en_ZA
dc.identifier.citationBMC Pulmonary Medicine. 2019 Aug 14;19(1):152
dc.identifier.ris TY - Journal Article AU - Tweed, Conor D AU - Crook, Angela M AU - Dawson, Rodney AU - Diacon, Andreas H AU - McHugh, Timothy D AU - Mendel, Carl M AU - Meredith, Sarah K AU - Mohapi, Lerato AU - Murphy, Michael E AU - Nunn, Andrew J AU - Phillips, Patrick P J AU - Singh, Kasha P AU - Spigelman, Melvin AU - Gillespie, Stephen H AB - Abstract Background The phase III REMoxTB study prospectively enrolled HIV-positive (with CD4+ count > 250 cells, not on anti-retroviral therapy) and HIV-negative patients. We investigated the incidence of adverse events and cure rates according to HIV status for patients receiving standard TB therapy in the trial. Methods Forty-two HIV-positive cases were matched to 220 HIV-negative controls by age, gender, ethnicity, and trial site using coarsened exact matching. Grade 3 and 4 adverse events (AEs) were summarised by MedDRA System Organ Class. Kaplan-Meier curves for time to first grade 3 or 4 AE were constructed according to HIV status with hazard ratios calculated. Patients were considered cured if they were culture negative 18 months after commencing therapy with ≥2 consecutive negative culture results. Results Twenty of 42 (47.6%) HIV-positive and 34 of 220 (15.5%) HIV-negative patients experienced ≥1 grade 3 or 4 AE, respectively. The majority of these were hepatobiliary disorders that accounted for 12 of 40 (30.0%) events occurring in 6 of 42 (14.3%) HIV-positive patients and for 15 of 60 (25.0%) events occurring in 9 of 220 (4.1%) HIV-negative patients. The median time to first grade 3 or 4 AE was 54 days (IQR 15.5–59.0) for HIV-positive and 29.5 days (IQR 9.0–119.0) for HIV-negative patients, respectively. The hazard ratio for experiencing a grade 3 or 4 AE among HIV-positive patients was 3.25 (95% CI 1.87–5.66, p < 0.01). Cure rates were similar, with 38 of 42 (90.5%) HIV-positive and 195 of 220 (88.6%) HIV-negative patients (p = 0.73) cured at 18 months. Conclusions HIV-positive patients receiving standard TB therapy in the REMoxTB study were at greater risk of adverse events during treatment but cure rates were similar when compared to a matched sample of HIV-negative patients. DA - 2019-08-14 DB - OpenUCT DP - University of Cape Town KW - Tuberculosis KW - Clinical trials KW - HIV KW - Adverse events LK - https://open.uct.ac.za PY - 2019 T1 - Toxicity related to standard TB therapy for pulmonary tuberculosis and treatment outcomes in the REMoxTB study according to HIV status TI - Toxicity related to standard TB therapy for pulmonary tuberculosis and treatment outcomes in the REMoxTB study according to HIV status UR - http://hdl.handle.net/11427/30692 ER - en_ZA
dc.identifier.urihttps://doi.org/10.1186/s12890-019-0907-6
dc.identifier.urihttp://hdl.handle.net/11427/30692
dc.identifier.vancouvercitationTweed CD, Crook AM, Dawson R, Diacon AH, McHugh TD, Mendel CM, et al. Toxicity related to standard TB therapy for pulmonary tuberculosis and treatment outcomes in the REMoxTB study according to HIV status. 2019; http://hdl.handle.net/11427/30692.en_ZA
dc.language.rfc3066en
dc.rights.holderThe Author(s).
dc.subjectTuberculosis
dc.subjectClinical trials
dc.subjectHIV
dc.subjectAdverse events
dc.titleToxicity related to standard TB therapy for pulmonary tuberculosis and treatment outcomes in the REMoxTB study according to HIV status
dc.typeJournal Article
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