Cochrane review: Impact of tuberculosis preventive therapy on tuberculosis and mortality in HIV‐infected children

Abstract

AbstractBackgroundChildren with HIV are at an increased risk of acquiring TB. Tuberculosis is a common cause of acute and chronic respiratory disease and death in HIV‐infected children living in areas of high TB prevalence. Even with treatment, HIV‐infected children with TB have a worse outcome than HIV uninfected children. Hence preventing TB infection and disease in HIV‐infected children is desirable and a potentially an important public health intervention. Isoniazid, an anti‐tuberculosis medication, has been used to effectively prevent TB in HIV uninfected children. There are currently no guidelines on the use of TB preventive therapy in HIV‐infected children.ObjectivesTo determine the impact of TB preventive therapy on TB incidence and death in HIV‐infected childrenSearch strategyWe searched the Cochrane Controlled Trials Register (CENTRAL/CCTR), Cochrane HIV/AIDS Group Specialized Register, MEDLINE/PubMed, EMBASE and AIDSearch. In addition we scanned reference lists, manually searched conference abstracts and contacted content experts.Selection criteriaWe included studies of HIV infected children randomised to receive TB preventive therapy or placebo, or alternative TB preventive regimen. Participants could be tuberculin skin test positive or negative.Data collection and analysisTwo authors independently used the study selection criteria, assessed methodological quality and extracted data. Effects were assessed using hazard ratios.Main resultsOne completed and two ongoing trials met the selection criteria for the review. The completed trial participants were HIV‐infected children, most of whom were not on antiretroviral therapy. Subjects‐ were randomised to isoniazid and cotrimoxazole or placebo and cotrimoxazole, given daily or three times a week. The mean length of follow‐up was 5.7 months. The trial showed a marked reduction in TB incidence and death in the isoniazid group. However there is as yet no long‐term follow up data on the durability of the protective effect or possible long term adverse events. This trial was also unable to assess the impact of isoniazid prophylaxis on children receiving antiretroviral therapy.Authors' conclusionsIsoniazid 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.Plain Language SummaryThe impact of tuberculosis preventive therapy on tuberculosis and death in HIV‐infected childrenTuberculosis (TB) is a common cause of severe lung disease and death in children infected with HIV, particularly those living in areas of high tuberculosis prevalence. Hence preventing TB infection and disease in HIV‐infected children is desirable and potentially an important major public health intervention. Isoniazid, a medication used in the treatment of TB, has been effectively used to prevent TB in HIV‐uninfected children exposed to TB. However, it is unclear what impact TB preventive therapy such as isoniazid has on the rate of TB or death if given to HIV‐infected children with and without exposure to TB. This review aimed to assess the impact of any TB preventive therapy on the rate of TB or death when given to HIV‐infected children. We found only one published randomised controlled trial investigating TB preventive therapy in HIV‐infected children. The trial showed a marked reduction in TB incidence and death in the group of children who received isoniazid as primary preventive therapy. Few adverse events occurred during the study and none were related to the isoniazid therapy. However there are currently no long‐term follow up data on the durability of the protective effect or possible long term adverse events. This trial was also unable to assess the impact of isoniazid prophylaxis on children receiving antiretroviral therapy. 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 adverse effects.