Effect of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV: randomised controlled trial.
To investigate the impact of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV.
                Two centre prospective double blind placebo controlled trial.
                Children aged > or =8 weeks with HIV.
                Isoniazid or placebo given with co-trimoxazole either daily or three times a week.
                Two tertiary healthcare centres in South Africa.
                Mortality, incidence of tuberculosis, and adverse events.
                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.
                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.
                Clinical Trials NCT00330304.
Isoniazid prophylaxis in HIV-infected children has the potential to play a major public health role by reducing TB incidence and death. However there is as yet not enough data to guide the duration of prophylaxis, given empirically, nor to support its use in children on HAART and in those living in low TB prevalence areas, other than in situations of known TB contact. Further studies are needed to assess whether TB preventive therapy is of benefit in all HIV-infected children irrespective of use of antiretroviral treatment, the optimal duration of preventive therapy or long term benefits and adverse events.