TY - JOUR
T1 - Use of antiretrovirals in HIV-infected children in a tuberculosis prevention trial
T2 - IMPAACT P1041
AU - Zeldow, B.
AU - Kim, Soyeon
AU - McSherry, G.
AU - Cotton, M. F.
AU - Jean-Philippe, P.
AU - Violari, A.
AU - Bobat, R.
AU - Nachman, S.
AU - Mofenson, L. M.
AU - Madhi, S. A.
AU - Mitchell, C.
N1 - Funding Information:
Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group was provided by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (U01 AI068632), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health, Bethesda, MD, USA (AI068632). This work was supported by the Statistical and Data Analysis Center at the Harvard School of Public Health, Boston, MA, USA, under NIAID cooperative agreements with the Pediatric AIDS Clinical Trials Group (5 U01 AI41110) and the IMPAACT Group (1 U01 AI068616). Support for the sites was provided by NIAID and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network (NICHD contract number N01-DK-9-001/HHSN267200800001C). Support for PJP comes from NIAID Contract No. HHSN272200800014C. The study was also funded by a grant from the Secure the Future Fund, a philanthropy program sponsored by Bristol-Myers Squibb, New York, NY, USA. Conflicts of interest: AV and MFC report receiving lecture fees from Abbott Laboratories, Chicago, IL, USA; SAM reports receiving fees from Pfizer (New York, NY, USA), GSK (Brentford, UK), Sanofi Pasteur (Swiftwater, PA, USA) and Novartis (Basel, Switzerland) for participation in expert boards and/or for supporting PhD students; and CM reports receiving lecture fees from MedImmune (Gaithersburg, MD, USA), GSK, and Novartis Vaccines. No other potential conflict of interest relevant to this article was reported.
Publisher Copyright:
© 2017 The Union.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - SETTING: International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1041, a tuberculosis (TB) prevention trial conducted among children enrolled from 2004 to 2008 during South Africa's roll-out of combination antiretroviral therapy (ART). OBJECTIVE: To estimate TB incidence and mortality and the effect of ART. DESIGN: Children were pre-screened to exclude TB disease and exposure, actively screened 3-monthly for TB exposure and symptoms, and provided post-exposure isoniazid prophylaxis therapy (IPT). TB diagnoses were definite, probable, or possible, and mortality all-cause. Testing was at the 5% significance level. RESULTS: In 539 children (aged 3-4 months) followed up for a median of 74 weeks (interquartile range [IQR] 48-116), incidence/100 person-years (py) was 10.67 (95%CI 8.47-13.26) for any TB and 2.89 (95%CI 1.85-4.31) for definite/probable TB. Any TB incidence was respectively 9.39, 13.59, and 9.83/100 py before, <180 days after, and ≥180 days after ART initiation. Adjusted analysis showed a non-significant increase in any TB (HR 1.32, 95%CI 0.71-2.52, P = 0.38) and a significant reduction in mortality (HR 0.39, 95%CI 0.17-0.82, P = 0.017) following ART initiation. CONCLUSIONS: ART reduced mortality but not TB incidence in human immunodeficiency virus (HIV) infected children in IMPAACT P1041, possibly attributable to active screening for TB exposure and symptoms with post-exposure IPT. Research into this as a strategy for TB prevention in high HIV-TB burden settings may be warranted.
AB - SETTING: International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1041, a tuberculosis (TB) prevention trial conducted among children enrolled from 2004 to 2008 during South Africa's roll-out of combination antiretroviral therapy (ART). OBJECTIVE: To estimate TB incidence and mortality and the effect of ART. DESIGN: Children were pre-screened to exclude TB disease and exposure, actively screened 3-monthly for TB exposure and symptoms, and provided post-exposure isoniazid prophylaxis therapy (IPT). TB diagnoses were definite, probable, or possible, and mortality all-cause. Testing was at the 5% significance level. RESULTS: In 539 children (aged 3-4 months) followed up for a median of 74 weeks (interquartile range [IQR] 48-116), incidence/100 person-years (py) was 10.67 (95%CI 8.47-13.26) for any TB and 2.89 (95%CI 1.85-4.31) for definite/probable TB. Any TB incidence was respectively 9.39, 13.59, and 9.83/100 py before, <180 days after, and ≥180 days after ART initiation. Adjusted analysis showed a non-significant increase in any TB (HR 1.32, 95%CI 0.71-2.52, P = 0.38) and a significant reduction in mortality (HR 0.39, 95%CI 0.17-0.82, P = 0.017) following ART initiation. CONCLUSIONS: ART reduced mortality but not TB incidence in human immunodeficiency virus (HIV) infected children in IMPAACT P1041, possibly attributable to active screening for TB exposure and symptoms with post-exposure IPT. Research into this as a strategy for TB prevention in high HIV-TB burden settings may be warranted.
KW - Antiretroviral therapy
KW - Mortality
KW - Perinatal HIV infection
KW - TB
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U2 - 10.5588/ijtld.16.0149
DO - 10.5588/ijtld.16.0149
M3 - Article
C2 - 28157463
AN - SCOPUS:85007566111
VL - 21
SP - 38-45 and i-iii
JO - International Journal of Tuberculosis and Lung Disease
JF - International Journal of Tuberculosis and Lung Disease
SN - 1027-3719
IS - 1
ER -