Shorter TB Prevention Regimen Well Tolerated in Children

SAN DIEGO, CA—Three months of the once-weekly rifapentine + isoniazid (INH) 12-dose regimen administered under directly observed therapy (DOT) offers “substantial advantages” over the standard 9-month regimen, 270 daily doses of INH treatment (9H) for latent tuberculosis (TB) in children, including being generally well tolerated, investigators reported during IDWeek 2012.

In adults, the PREVENT TB Study (TBTC Study 26/ACTG 5259) found 3 months of once-weekly rifapentine 900mg + INH 900mg DOT was at least as effective as 9 months of daily INH in a population of mostly HIV-seronegative adults, reported Elsa Villarino MD, from the Centers for Disease Control and Prevention, Atlanta, GA,

This study reported on the regimen’s tolerability in children ages 2–17 years who were close contacts of those with infectious TB and were enrolled between June 2001 and December 2010. To enrich the study population, “enrollment of children <12 years into PREVENT TB was extended 22 months past the last enrollment of HIV negative adults and adolescents,” Dr. Villarino noted.

Of the 1,058 children (n=539, ages 2–11; n=519, ages 12–17) from the United States, Canada, Brazil, Hong Kong, and Spain in the study, 1,032 received at least one dose of therapy and were included in the tolerability analysis, 539 in the weekly 3-month regimen and 493 in the daily 9-month regimen. Children were treated with protocol-specified, age- and weight-adjusted treatment regimens; those unable to swallow whole tablets were administered a slurry of crushed tablets in food.

Among all participants, median age was 11 years (range, 4–15); 51% were male; 71% were white; and 0.5% were infected with HIV. In the U.S. and Canadian populations, 73% were Hispanic. A total of 88.2% of children completed the weekly 3-month regimen vs. 80.3% of the daily 9-month regimen (P=0.001). As was observed in adults, the shorter regimen resulted in higher treatment complications in children, with more cases of possible drug hypersensitivity than the 9-month regimen (P=0.02). Drug hypersensitivity was noted as mild-to-moderate and is currently under investigation.

No differences were observed in Grade 3–5 toxicity between the two regimens and there were no cases of hepatotoxicity. Treatment discontinuation due to adverse events was similar between the two arms. A high completion rate of 96% was seen for in the intent-to-treat population. All children were required to have a 990-day (33 months) follow-up for effectiveness of the regimen. The remaining 4% of participants have not reached the 990-day mark and will continue till October 2013.  After 1 year of follow-up, TB disease was seen in 3 cases in the 9H treatment arm and 0 cases in the 3HP arm (rate difference -0.81%).

Dr. Villarino concluded, “Effectiveness for prevention of TB was estimated to be as good as the 9H treatment.  This new combination can be a new tool for a very high impact public health intervention in preventing pediatric TB.”