Diagnosis and Management of Tuberculosis in HIV-infected Children
Objectives: Management of HIV-infected children with tuberculosis (TB) is challenging. The objective of this study was to assess current treatment and outcomes in a resource-rich setting in the era of highly active antiretroviral therapy (HAART).
Methods: A retrospective case-note review of coinfected children was carried out in a large UK-based HIV family clinic.
Results: Of 328 HIV-infected children, 18 were diagnosed and treated for active TB.
TB presentation led to HIV diagnosis in eight of these 18 children. TB was confirmed microbiologically in 33% of children. Fifteen of the 18 children presented with pulmonary TB, and three with extrapulmonary TB (EPTB). Immunological status at TB diagnosis did not predict EPTB. The mean CD4 T-cell count at TB presentation was 402 cells/µL (mean CD4 percentage 16%), with a range of 0-790 cells/µL (0-34%). In seven children concurrently treated with HAART and anti-tuberculous therapy (ATT), therapeutic drug monitoring (TDM) guided management. No immune reconstitution disease occurred. There was one death, unrelated to TB, 2 years after completion of ATT.
Conclusions: An HIV test should be considered in all children diagnosed with TB, especially if there are epidemiological risk factors. Our experience shows that, even with deferral of HAART in concurrently infected children, good therapeutic responses to ATT can be achieved. Where necessary, TDM guiding concurrent HAART and ATT can facilitate good clinical and virological responses.
Each year, one million children world-wide become newly infected with tuberculosis (TB) and 420 000 with HIV. Coinfection with both organisms, the 'cursed duet', is an increasing global emergency. TB infection itself can lower the CD4 cell count in children, and exacerbates the immunodeficiency caused by HIV. Compared with HIV-uninfected children, HIV-infected children have a six-times greater risk of dying from TB.
The vast majority of coinfected children live in resource-limited countries, with HIV prevalence rates among TB-infected children of 10-60%. Childhood coinfection has also been reported from resource-rich countries with lower TB endemicity. Studies of coinfection in such settings have described the presentation and diagnosis of TB in HIV-infected children.
Diagnosis of TB in HIV-infected children is notoriously challenging. The optimal approach to the diagnosis and management of coinfected children is still not clear, and may differ between areas of high and low TB endemicity. Whether newer diagnostic tests for TB can play a role in HIV-infected children remains to be fully evaluated. Although the World Health Organization (WHO) have recently issued guidelines for the use of highly active antiretroviral therapy (HAART) in TB-infected children, these largely extrapolate from adult data. Pharmacokinetic data to guide concurrent anti-tuberculous therapy (ATT) and HAART are sparse.
To clarify these issues and characterize the difficulties in diagnosing and treating coinfected children in areas of HAART availability, we undertook a review of our own practice over the last 15 years.
Abstract and Introduction
Abstract
Objectives: Management of HIV-infected children with tuberculosis (TB) is challenging. The objective of this study was to assess current treatment and outcomes in a resource-rich setting in the era of highly active antiretroviral therapy (HAART).
Methods: A retrospective case-note review of coinfected children was carried out in a large UK-based HIV family clinic.
Results: Of 328 HIV-infected children, 18 were diagnosed and treated for active TB.
TB presentation led to HIV diagnosis in eight of these 18 children. TB was confirmed microbiologically in 33% of children. Fifteen of the 18 children presented with pulmonary TB, and three with extrapulmonary TB (EPTB). Immunological status at TB diagnosis did not predict EPTB. The mean CD4 T-cell count at TB presentation was 402 cells/µL (mean CD4 percentage 16%), with a range of 0-790 cells/µL (0-34%). In seven children concurrently treated with HAART and anti-tuberculous therapy (ATT), therapeutic drug monitoring (TDM) guided management. No immune reconstitution disease occurred. There was one death, unrelated to TB, 2 years after completion of ATT.
Conclusions: An HIV test should be considered in all children diagnosed with TB, especially if there are epidemiological risk factors. Our experience shows that, even with deferral of HAART in concurrently infected children, good therapeutic responses to ATT can be achieved. Where necessary, TDM guiding concurrent HAART and ATT can facilitate good clinical and virological responses.
Introduction
Each year, one million children world-wide become newly infected with tuberculosis (TB) and 420 000 with HIV. Coinfection with both organisms, the 'cursed duet', is an increasing global emergency. TB infection itself can lower the CD4 cell count in children, and exacerbates the immunodeficiency caused by HIV. Compared with HIV-uninfected children, HIV-infected children have a six-times greater risk of dying from TB.
The vast majority of coinfected children live in resource-limited countries, with HIV prevalence rates among TB-infected children of 10-60%. Childhood coinfection has also been reported from resource-rich countries with lower TB endemicity. Studies of coinfection in such settings have described the presentation and diagnosis of TB in HIV-infected children.
Diagnosis of TB in HIV-infected children is notoriously challenging. The optimal approach to the diagnosis and management of coinfected children is still not clear, and may differ between areas of high and low TB endemicity. Whether newer diagnostic tests for TB can play a role in HIV-infected children remains to be fully evaluated. Although the World Health Organization (WHO) have recently issued guidelines for the use of highly active antiretroviral therapy (HAART) in TB-infected children, these largely extrapolate from adult data. Pharmacokinetic data to guide concurrent anti-tuberculous therapy (ATT) and HAART are sparse.
To clarify these issues and characterize the difficulties in diagnosing and treating coinfected children in areas of HAART availability, we undertook a review of our own practice over the last 15 years.
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