One month of rifapentine + isoniazid no worse than 9 months isoniazid for HIV patients at high risk for TB or with latent TB

Reference

Swindells S, Ramchandani R, Gupta A, et al, for the BRIEF TB/A5279 Study Team. One month of rifapentine plus isoniazid to prevent HIV-related tuberculosis. N Engl J Med 2019; 380(11):1001-1011.

Synopsis

HIV and TB coinfection is common, with high morbidity and mortality. Although treatment of latent TB is recommended for patients with HIV infection, it is rarely used in practice because of concerns about adherence, cost, and emerging drug resistance in partially treated patients. This study identified patients 13 years or older with HIV infection who had either latent TB or who lived in an area with a high prevalence of TB infection (> 60 cases/100,000). The median age of patients was 35 years, 54% were female, and approximately half lived in Africa with the rest residing in Asia (8%), South America (24%), or North America (16%). Most patients (87%) had a CD4 count of more than 250 cells/mm3, approximately half were receiving antiretroviral therapy at study entry (most of the remainder initiated therapy within 1 month of study entry), and 21% had a positive TB skin test result (those with active TB were excluded). The researchers randomized 3000 persons to receive either 1 month of rifapentine plus isoniazid or a 9-month regimen of isoniazid alone and followed them for a median of 3.3 years. All patients also received pyridoxine. Rifapentine was dosed by weight in a range from 300 mg to 600 mg, while isoniazid was given in a dose of 300 mg once daily for all patients. Groups were balanced at study entry and analysis was by intention to treat. The primary outcome was a composite of the time to first diagnosis of active TB, death from TB, or death from an unknown cause. The primary outcome occurred in 2% of patients in each group, with active TB responsible for 29/32 events in the 1-month group and 26/33 events in the 9-month group. Those with latent TB were at higher risk of one of these outcome events in both treatment groups. Discontinuation due to adverse events occurred in 1% of the 1-month group and 2% of the 9-month group, and adherence was better in the shorter course group (97% vs 90%; P < .001).