Use of antiretrovirals in HIV-infected children in a tuberculosis prevention trial: IMPAACT P1041

B. Zeldow, Soyeon Kim, George McSherry, M. F. Cotton, P. Jean-Philippe, A. Violari, R. Bobat, S. Nachman, L. M. Mofenson, S. A. Madhi, C. Mitchell

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Abstract

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.

Original languageEnglish (US)
JournalInternational Journal of Tuberculosis and Lung Disease
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2017

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Acquired Immunodeficiency Syndrome
Tuberculosis
Mothers
Clinical Trials
HIV
Pediatrics
Post-Exposure Prophylaxis
Mortality
Incidence
Isoniazid
Therapeutics
South Africa

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Infectious Diseases

Cite this

Zeldow, B. ; Kim, Soyeon ; McSherry, George ; Cotton, M. F. ; Jean-Philippe, P. ; Violari, A. ; Bobat, R. ; Nachman, S. ; Mofenson, L. M. ; Madhi, S. A. ; Mitchell, C. / Use of antiretrovirals in HIV-infected children in a tuberculosis prevention trial : IMPAACT P1041. In: International Journal of Tuberculosis and Lung Disease. 2017 ; Vol. 21, No. 1.
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abstract = "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.",
author = "B. Zeldow and Soyeon Kim and George McSherry and Cotton, {M. F.} and P. Jean-Philippe and A. Violari and R. Bobat and S. Nachman and Mofenson, {L. M.} and Madhi, {S. A.} and C. Mitchell",
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Zeldow, B, Kim, S, McSherry, G, Cotton, MF, Jean-Philippe, P, Violari, A, Bobat, R, Nachman, S, Mofenson, LM, Madhi, SA & Mitchell, C 2017, 'Use of antiretrovirals in HIV-infected children in a tuberculosis prevention trial: IMPAACT P1041', International Journal of Tuberculosis and Lung Disease, vol. 21, no. 1. https://doi.org/10.5588/ijtld.16.0149

Use of antiretrovirals in HIV-infected children in a tuberculosis prevention trial : IMPAACT P1041. / Zeldow, B.; Kim, Soyeon; McSherry, George; Cotton, M. F.; Jean-Philippe, P.; Violari, A.; Bobat, R.; Nachman, S.; Mofenson, L. M.; Madhi, S. A.; Mitchell, C.

In: International Journal of Tuberculosis and Lung Disease, Vol. 21, No. 1, 01.01.2017.

Research output: Contribution to journalArticle

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, George

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.

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.

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