TY - JOUR
T1 - Substantially Higher and Earlier Occurrence of Anti-Tuberculosis Drug-Related Adverse Reactions in HIV Coinfected Tuberculosis Patients
T2 - A Matched-Cohort Study
AU - Matono, Takashi
AU - Nishijima, Takeshi
AU - Teruya, Katsuji
AU - Morino, Eriko
AU - Takasaki, Jin
AU - Gatanaga, Hiroyuki
AU - Kikuchi, Yoshimi
AU - Kaku, Mitsuo
AU - Oka, Shinichi
N1 - Funding Information:
The authors thank the physicians, nurses, and other staff at the AIDS Clinical Center and Department of Respiratory Medicine, NCGM, for their excellent work. We also thank Tetsuya Mizoue and the staff at the Department of Epidemiology and Prevention, Center for Clinical Science, NCGM, for advice regarding our study design. Funding: This study was supported, in part, by research grants from the Japanese Agency for Medical Research and Development, AMED. The funder had no role in this study such as study design, data collection, or decision to publish.
Publisher Copyright:
© Copyright 2017, Mary Ann Liebert, Inc. 2017.
PY - 2017/11
Y1 - 2017/11
N2 - Little information exists on the frequency, severity, and timing of first-line anti-Tuberculosis drug-related adverse events (TB-AEs) in HIV-Tuberculosis coinfected (HIV-TB) patients in the antiretroviral therapy (ART) era. This matched-cohort study included HIV-TB patients as cases and HIV-uninfected tuberculosis (non-HIV-TB) patients as controls. Tuberculosis was culture-confirmed in both groups. Cases were matched to controls in a 1:4 ratio on age, sex, and year of diagnosis. TB-AEs were defined as Grade 2 or higher requiring drug discontinuation/regimen change. From 2003 to 2015, 94 cases and 376 controls were analyzed (95% men, 98% Asians). Standard four-drug combination therapy was initiated in 91% of cases and 89% of controls (p = 0.45). Cases had a higher frequency of TB-AE [51% (48/94) vs. 10% (39/376), p < 0.001]. Their major TB-AEs were fever (19%), rash (11%), and neutropenia (11%). TB-AEs were more severe in cases [Grade 3 or higher: cases (71%, 34/48) vs. controls (49%, 19/39), p < 0.001]. The time from treatment initiation to TB-AE was shorter in cases [median 18 (interquartile range 12-28) vs. 27 (15-57) days, p = 0.027], and 73% of TB-AEs in cases occurred within 4 weeks of starting anti-Tuberculosis treatment. HIV infection was an independent risk factor for TB-AEs in the multivariate Cox analysis [adjusted HR (aHR): 6.96; 95% confidence interval: 3.93-12.3]. TB-AEs occurred more frequently in HIV-TB than in non-HIV-TB patients, and were more severe. The majority of TB-AEs occurred within 4 weeks of initiating anti-Tuberculosis treatment. Because TB-AEs may delay ART initiation, careful monitoring during this period is warranted in coinfected patients.
AB - Little information exists on the frequency, severity, and timing of first-line anti-Tuberculosis drug-related adverse events (TB-AEs) in HIV-Tuberculosis coinfected (HIV-TB) patients in the antiretroviral therapy (ART) era. This matched-cohort study included HIV-TB patients as cases and HIV-uninfected tuberculosis (non-HIV-TB) patients as controls. Tuberculosis was culture-confirmed in both groups. Cases were matched to controls in a 1:4 ratio on age, sex, and year of diagnosis. TB-AEs were defined as Grade 2 or higher requiring drug discontinuation/regimen change. From 2003 to 2015, 94 cases and 376 controls were analyzed (95% men, 98% Asians). Standard four-drug combination therapy was initiated in 91% of cases and 89% of controls (p = 0.45). Cases had a higher frequency of TB-AE [51% (48/94) vs. 10% (39/376), p < 0.001]. Their major TB-AEs were fever (19%), rash (11%), and neutropenia (11%). TB-AEs were more severe in cases [Grade 3 or higher: cases (71%, 34/48) vs. controls (49%, 19/39), p < 0.001]. The time from treatment initiation to TB-AE was shorter in cases [median 18 (interquartile range 12-28) vs. 27 (15-57) days, p = 0.027], and 73% of TB-AEs in cases occurred within 4 weeks of starting anti-Tuberculosis treatment. HIV infection was an independent risk factor for TB-AEs in the multivariate Cox analysis [adjusted HR (aHR): 6.96; 95% confidence interval: 3.93-12.3]. TB-AEs occurred more frequently in HIV-TB than in non-HIV-TB patients, and were more severe. The majority of TB-AEs occurred within 4 weeks of initiating anti-Tuberculosis treatment. Because TB-AEs may delay ART initiation, careful monitoring during this period is warranted in coinfected patients.
KW - HIV
KW - adverse reactions
KW - anti-Tuberculosis drugs
KW - antiretroviral therapy
KW - tuberculosis
UR - http://www.scopus.com/inward/record.url?scp=85032678768&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032678768&partnerID=8YFLogxK
U2 - 10.1089/apc.2017.0116
DO - 10.1089/apc.2017.0116
M3 - Article
C2 - 29087745
AN - SCOPUS:85032678768
VL - 31
SP - 455
EP - 462
JO - AIDS Patient Care and STDs
JF - AIDS Patient Care and STDs
SN - 1087-2914
IS - 11
ER -