Effect of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV: randomised controlled trial.
OBJECTIVE
To investigate the impact of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV.


METHODS
Two centre prospective double blind placebo controlled trial.


METHODS
Children aged > or =8 weeks with HIV.


METHODS
Isoniazid or placebo given with co-trimoxazole either daily or three times a week.


METHODS
Two tertiary healthcare centres in South Africa.


METHODS
Mortality, incidence of tuberculosis, and adverse events.


RESULTS
Data on 263 children (median age 24.7 months) were available when the data safety monitoring board recommended discontinuing the placebo arm; 132 (50%) were taking isoniazid. Median follow-up was 5.7 (interquartile range 2.0-9.7) months. Mortality was lower in the isoniazid group than in the placebo group (11 (8%) v 21 (16%), hazard ratio 0.46, 95% confidence interval 0.22 to 0.95, P=0.015) by intention to treat analysis. The benefit applied across Centers for Disease Control clinical categories and in all ages. The reduction in mortality was similar in children on three times a week or daily isoniazid. The incidence of tuberculosis was lower in the isoniazid group (5 cases, 3.8%) than in the placebo group (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 children in the placebo group.


CONCLUSIONS
Prophylaxis with isoniazid has an early survival benefit and reduces incidence of tuberculosis in children with HIV. Prophylaxis may offer an effective public health intervention to reduce mortality in such children in settings with a high prevalence of tuberculosis.


BACKGROUND
Clinical Trials NCT00330304.
Zar
Heather J
HJ
School of Child and Adolescent Health, Red Cross Children's Hospital, University of Cape Town, South Africa. hzar@ich.uct.ac.za
Cotton
Mark F
MF
Strauss
Stanzi
S
Karpakis
Janine
J
Hussey
Gregory
G
Schaaf
H Simon
HS
Rabie
Helena
H
Lombard
Carl J
CJ
D017954:Africa South of the Sahara / Q000453:epidemiology; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003906:Developing Countries; D004311:Double-Blind Method; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology; D006297:Health Services Accessibility; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007538:Isoniazid / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000401:mortality
D044966:Anti-Retroviral Agents; D000995:Antitubercular Agents; D007538:Isoniazid