Severe manifestations of extrapulmonary tuberculosis in HIV-infected children initiating antiretroviral therapy before 2 years of age

• Published in: Archives of disease in childhood Vol. 99; no. 11; pp. 998 - 1003
• Main Authors: Walters, Elisabetta, Duvenhage, Joanie, Draper, Heather R, Hesseling, Anneke C, Van Wyk, Susan S, Cotton, Mark F, Rabie, Helena
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group 01-11-2014; BMJ Publishing Group Ltd; BMJ Publishing Group LTD
• Subjects: Age; Antiretroviral agents; Antiretroviral drugs; Antiretroviral Therapy, Highly Active - methods; Bacterial diseases; Biological and medical sciences; Care and treatment; Children & youth; Clinics; Cohort Studies; Communicable Diseases; Complications and side effects; Drug therapy; Female; Follow-Up Studies; General aspects; Guidelines; Highly active antiretroviral therapy; HIV infection in children; HIV Infections - drug therapy; Human bacterial diseases; Humans; Incidence; Infant; Infectious diseases; Laboratories; Male; Medical sciences; Miscellaneous; Mortality; National Standards; Pediatric HIV infections; Prevention and actions; Public health; Public health. Hygiene; Public health. Hygiene-occupational medicine; Retrospective Studies; Risk Factors; Software; South Africa - epidemiology; Statistical Analysis; Tuberculosis; Tuberculosis - diagnosis; Tuberculosis and atypical mycobacterial infections; Young Children; South Africa; United Kingdom; Human; Immunopathology; Pediatrics; Antiretroviral agent; Pharmacotherapy; AIDS; Mycobacterial infection; Immune deficiency; Infection; Chemotherapy; Treatment; Tuberculosis; Extrapulmonary; Viral disease; Bacteriosis; Antiviral; Severe; Child; Age; Public health; Infants; HIV; Antiretroviral Therapy
• ISSN: 0003-9888; 1468-2044
• DOI: 10.1136/archdischild-2013-305509

Background Early initiation of antiretroviral therapy (ART) in HIV-infected infants reduces mortality and opportunistic infections including tuberculosis (TB). However, young HIV-infected children remain at high risk of TB disease following mycobacterial infection. We document the spectrum of TB disease in HIV-infected children <2 years of age on ART. Methods Retrospective cohort study; records of children <2 years of age initiating routine ART at Tygerberg Children's Hospital, Cape Town, January 2003–December 2010 were reviewed. Clinical data at ART initiation (baseline) and TB episodes after ART initiation, to June 2012, were recorded. TB immune reconstitution syndrome (TB-IRIS) and incident TB were defined as TB diagnosed within 3 months, and >3 months after, ART initiation respectively. Baseline characteristics were compared in children with TB-IRIS and those with incident TB. Results In 494 children, median follow-up time on ART was 10.7 months. Fifty-five TB treatment episodes occurred after ART initiation: 23 (42%) TB-IRIS (incidence 21.9/100 person years (py)) and 32 (58%) incident TB (incidence 3.9/100 py). Children with TB-IRIS and those with incident TB had similar baseline characteristics. Eight of 10 cases of extrapulmonary TB were severe: 4 IRIS (2 meningitis, 1 disseminated, 1 pericarditis) and 4 incident cases (1 each miliary, meningitis, pericarditis and spinal). Fifty-one children (10%) died (mortality rate 5.96/100 py). Starting ART at <1 year of age approached significance as a risk factor for TB-IRIS (adjusted OR (AOR) 8.64, p=0.06); weight-for-age Z score <−2 predicted death (AOR 6.37, p<0.001). Conclusions Severe TB manifestations were observed among young HIV-infected children on ART.