PMID- 31412895
OWN - NLM
STAT- MEDLINE
DCOM- 20200211
LR  - 20210312
IS  - 1471-2466 (Electronic)
IS  - 1471-2466 (Linking)
VI  - 19
IP  - 1
DP  - 2019 Aug 14
TI  - Toxicity related to standard TB therapy for pulmonary tuberculosis and treatment 
      outcomes in the REMoxTB study according to HIV status.
PG  - 152
LID - 10.1186/s12890-019-0907-6 [doi]
LID - 152
AB  - 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.
FAU - Tweed, Conor D
AU  - Tweed CD
AUID- ORCID: 0000-0001-6021-8237
AD  - MRC Clinical Trials Unit at University College London, London, UK. 
      c.tweed@ucl.ac.uk.
FAU - Crook, Angela M
AU  - Crook AM
AD  - MRC Clinical Trials Unit at University College London, London, UK.
FAU - Dawson, Rodney
AU  - Dawson R
AD  - University of Cape Town Lung Institute, Cape Town, South Africa.
FAU - Diacon, Andreas H
AU  - Diacon AH
AD  - TASK Applied Science, Cape Town, South Africa.
FAU - McHugh, Timothy D
AU  - McHugh TD
AD  - Division of Infection and Immunity, University College London, London, UK.
FAU - Mendel, Carl M
AU  - Mendel CM
AD  - TB Alliance, New York, USA.
FAU - Meredith, Sarah K
AU  - Meredith SK
AD  - MRC Clinical Trials Unit at University College London, London, UK.
FAU - Mohapi, Lerato
AU  - Mohapi L
AD  - Perinatal HIV Research Unit, Johannesburg, South Africa.
FAU - Murphy, Michael E
AU  - Murphy ME
AD  - Division of Infection and Immunity, University College London, London, UK.
FAU - Nunn, Andrew J
AU  - Nunn AJ
AD  - MRC Clinical Trials Unit at University College London, London, UK.
FAU - Phillips, Patrick P J
AU  - Phillips PPJ
AD  - Division of Pulmonology, University of San Francisco, San Francisco, USA.
FAU - Singh, Kasha P
AU  - Singh KP
AD  - The Doherty Institute for Infection and Immunity, University of Melbourne and 
      Royal Melbourne Hospital, Parkville, Australia.
FAU - Spigelman, Melvin
AU  - Spigelman M
AD  - TB Alliance, New York, USA.
FAU - Gillespie, Stephen H
AU  - Gillespie SH
AD  - University of St Andrews Medical School, St Andrews, UK.
LA  - eng
GR  - MC_U122888469/MRC_/Medical Research Council/United Kingdom
GR  - MC_UU_12023/27/MRC_/Medical Research Council/United Kingdom
GR  - R21 MH083308/MH/NIMH NIH HHS/United States
GR  - UM1 AI069453/AI/NIAID NIH HHS/United States
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20190814
PL  - England
TA  - BMC Pulm Med
JT  - BMC pulmonary medicine
JID - 100968563
RN  - 0 (Antitubercular Agents)
RN  - 2KNI5N06TI (Pyrazinamide)
RN  - 8G167061QZ (Ethambutol)
RN  - V83O1VOZ8L (Isoniazid)
RN  - VJT6J7R4TR (Rifampin)
SB  - IM
MH  - Adult
MH  - Antitubercular Agents/*adverse effects/therapeutic use
MH  - Ethambutol/adverse effects/therapeutic use
MH  - Female
MH  - *HIV Seropositivity
MH  - Humans
MH  - Incidence
MH  - Isoniazid/adverse effects/therapeutic use
MH  - Linear Models
MH  - Male
MH  - Multivariate Analysis
MH  - Prospective Studies
MH  - Pyrazinamide/adverse effects/therapeutic use
MH  - Rifampin/adverse effects/therapeutic use
MH  - Risk Factors
MH  - Treatment Outcome
MH  - Tuberculosis, Pulmonary/*drug therapy
MH  - United Kingdom
PMC - PMC6694514
OTO - NOTNLM
OT  - Adverse events
OT  - Clinical trials
OT  - HIV
OT  - Tuberculosis
COIS- None declared.
EDAT- 2019/08/16 06:00
MHDA- 2020/02/12 06:00
PMCR- 2019/08/14
CRDT- 2019/08/16 06:00
PHST- 2018/11/16 00:00 [received]
PHST- 2019/07/26 00:00 [accepted]
PHST- 2019/08/16 06:00 [entrez]
PHST- 2019/08/16 06:00 [pubmed]
PHST- 2020/02/12 06:00 [medline]
PHST- 2019/08/14 00:00 [pmc-release]
AID - 10.1186/s12890-019-0907-6 [pii]
AID - 907 [pii]
AID - 10.1186/s12890-019-0907-6 [doi]
PST - epublish
SO  - BMC Pulm Med. 2019 Aug 14;19(1):152. doi: 10.1186/s12890-019-0907-6.