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



To estimate TB incidence and mortality and the effect of ART.



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.



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.



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.
Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts, USA.
B
B
Zeldow
Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts, USA; Department of Biostatistics, Rutgers School of Public Health, Newark, New Jersey, USA.
S
S
Kim
Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
G
G
McSherry
Department of Paediatrics and Child Health, Stellenbosch University, Tygerberg, South Africa.
M F
MF
Cotton
Henry Jackson Foundation-National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
P
P
Jean-Philippe
Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
A
A
Violari
Department of Paediatrics and Child Health, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, South Africa.
R
R
Bobat
State University of New York at Stony Brook, Stony Brook, New York, USA.
S
S
Nachman
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, Maryland, USA; Elizabeth Glaser Pediatric AIDS Foundation, Washington DC, USA.
L M
LM
Mofenson
Respiratory and Meningeal Pathogens Research Unit, Medical Research Council, University of the Witwatersrand, Johannesburg, South Africa.
S A
SA
Madhi
University of Miami Miller School of Medicine, Miami, Florida, USA.
C
C
Mitchell
D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007223:Infant; D007538:Isoniazid / Q000627:therapeutic use; D008297:Male; D016016:Proportional Hazards Models; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D014376:Tuberculosis / Q000453:epidemiology / Q000517:prevention & control*
D044966:Anti-Retroviral Agents; D007538:Isoniazid