Mortality in HIV-Infected Children Predicted by Urine TB Lipoarabinomannan

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Six-month mortality was 3.7-fold higher among lipoarabinomannan-positive compared to lipoarabinomannan-negative children.
Six-month mortality was 3.7-fold higher among lipoarabinomannan-positive compared to lipoarabinomannan-negative children.

Among HIV-infected children initiating antiretroviral therapy, positive urine lipoarabinomannan (LAM) results were associated with a 4.9-fold higher mortality risk compared with negative urine LAM results, according to data from a recent study published in Clinical Infectious Diseases.

In this prospective study (ClinicalTrials.gov identifier: NCT02063880) of patients enrolled in a trial comparing antiretroviral initiation times, researchers evaluated 137 hospitalized children in Kenya who had HIV and had never received antiretroviral therapy. The children were 12 years of age or younger (median age 26 months; 54.0% male; 70.1% severely immunosuppressed). The goal was to determine the association of LAM results and mortality. Tuberculosis testing was performed with liquid cultures of 2 sputa or gastric aspirates. LAM testing was performed on fresh urine, and a color change corresponding to ≥1 grade was considered positive.

Confirmed tuberculosis and unconfirmed tuberculosis were reported in 6.6% and 43.1% of participants, respectively. The remainder of participants (50.4%) were considered unlikely to have tuberculosis. Tuberculosis treatment was initiated in 37.5% of patients.

A total of 11.0% of children were LAM positive, of whom 33.3% had confirmed tuberculosis and 20.0% had unconfirmed tuberculosis. Tuberculosis treatment was initiated in 46.7% of children who were LAM positive.

During the 6-month follow-up, 15.3% of children died, with a cumulative mortality incidence of 40/100 person-years. After adjustment for baseline CD4 levels, age, and parent-trial arm, the risk for 6-month mortality was significantly higher among LAM-positive children compared with LAM-negative children (hazard ratio [HR] 4.92; P =.002). Mortality risk remained high in the subgroup of children with confirmed or unconfirmed tuberculosis (HR 9.13; P =.002) but not in children with unlikely tuberculosis (HR 1.68; P =.50).

According to the study authors, HIV-infected hospitalized children initiating antiretroviral therapy are part of “a group in which tuberculosis diagnosis is often missed, and in whom early tuberculosis treatment is lifesaving.” They concluded that the results “provide evidence to support [the World Health Organization's] recommendation that urine LAM is helpful for tuberculosis diagnosis in severely ill HIV-infected children, including those at greatest mortality risk. Benefits of urine LAM include its rapid point-of-care platform, low cost, and readily accessible sample type.”

Reference

LaCourse SM, Cranmer LM, Njuguna IN, et al. Urine TB lipoarabinomannan (LAM) predicts mortality in hospitalized HIV-infected children [published online January 6, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy011

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