Effect of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV: randomised controlled trial

doi:10.1136/bmj.39000.486400.55

BMJ 2007;334:136 (20 January), doi:10.1136/bmj.39000.486400.55 (published 3 November 2006)

Research

Effect of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV: randomised controlled trial

Heather J Zar, associate professor¹, Mark F Cotton, associate professor², Stanzi Strauss, research medical officer¹, Janine Karpakis, research medical officer², Gregory Hussey, professor¹, H Simon Schaaf, associate professor², Helena Rabie, clinical researcher², Carl J Lombard, senior statistician³

¹ School of Child and Adolescent Health, Red Cross Children's Hospital, University of Cape Town, South Africa, ² Department of Paediatrics and Child Health, Tygerberg Children's Hospital, Stellenbosch University, South Africa, ³ Biostatistics Unit, Medical Research Council, South Africa

Correspondence to: H Zar hzar{at}ich.uct.ac.za

Objectives To investigate theimpact of isoniazid prophylaxis on mortality and incidence oftuberculosis in children with HIV.

Design Two centre prospectivedouble blind placebo controlled trial.

Participants Children aged $≥$ 8weeks with HIV.

Interventions Isoniazid or placebogiven with co-trimoxazole either daily or three times a week.

Setting Two tertiary healthcarecentres in South Africa.

Main outcome measures Mortality,incidence of tuberculosis, and adverse events.

Results Data on 263 children(median age 24.7 months) were available when the data safetymonitoring board recommended discontinuing the placebo arm;132 (50%) were taking isoniazid. Median follow-up was 5.7 (interquartilerange 2.0-9.7) months. Mortality was lower in the isoniazidgroup than in the placebo group (11 (8%) v 21 (16%), hazardratio 0.46, 95% confidence interval 0.22 to 0.95, P=0.015) byintention to treat analysis. The benefit applied across Centersfor Disease Control clinical categories and in all ages. Thereduction in mortality was similar in children on three timesa week or daily isoniazid. The incidence of tuberculosis waslower in the isoniazid group (5 cases, 3.8%) than in the placebogroup (13 cases, 9.9%) (hazard ratio 0.28, 0.10 to 0.78, P=0.005).All cases of tuberculosis confirmed by culture were in childrenin the placebo group.

Conclusions Prophylaxis withisoniazid has an early survival benefit and reduces incidenceof tuberculosis in children with HIV. Prophylaxis may offeran effective public health intervention to reduce mortalityin such children in settings with a high prevalence of tuberculosis.

Trial registration. ClinicalTrials NCT00330304

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to StumbleUpon StumbleUpon Add to Technorati Technorati What's this?

Relevant Articles

Tuberculosis in resource poor countries: Robert Colebunders, Ludwig Apers, Greet Dieltiens, and William Worodria
BMJ 2007 334: 105-106. [Extract] [Full Text] [PDF]

Effect of preventive treatment for tuberculosis in adults infected with HIV: systematic review of randomised placebo controlled trials: David Wilkinson, S B Squire, and Paul Garner
BMJ 1998 317: 625-629. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

Boulle, A., Eley, B. (2009). Commentary: Reducing HIV-associated tuberculosis in children. Int J Epidemiol 0: dyp301v1-dyp301 [Full text]
Gray, D., Nuttall, J., Lombard, C., Davies, M.-a., Workman, L., Apolles, P., Eley, B., Cotton, M., Zar, H. (2009). Low Rates of Hepatotoxicity in HIV-infected Children on Anti-retroviral Therapy with and Without Isoniazid Prophylaxis. J Trop Pediatr 0: fmp079v1-fmp079 [Abstract] [Full text]
Edmonds, A., Lusiama, J., Napravnik, S., Kitetele, F., Van Rie, A., Behets, F. (2009). Anti-retroviral therapy reduces incident tuberculosis in HIV-infected children. Int J Epidemiol 0: dyp208v1-dyp208 [Abstract] [Full text]
(2007). Preventing TB in HIV-Infected Children. JWatch Infect. Diseases 2007: 3-3 [Full text]
Colebunders, R., Apers, L., Dieltiens, G., Worodria, W. (2007). Tuberculosis in resource poor countries. BMJ 334: 105-106 [Full text]

Rapid Responses:

Read all Rapid Responses

Pharmacokinetics of isoniazid formulation needs to be addressed: Joseph F Standing
bmj.com, 21 Jan 2007 [Full text]
Re: Pharmacokinetics of isoniazid formulation needs to be addressed: Heather J Zar, et al.
bmj.com, 26 Jan 2007 [Full text]
HIV testing in TB patients, are we there yet: Ismael Musa Balluz, et al.
bmj.com, 20 Sep 2007 [Full text]