Clinical Pearls & Morning Reports
Published March 13, 2019
Approximately 1000 patients with human immunodeficiency virus (HIV) infection die from tuberculosis each day, including many who are receiving antiretroviral therapy. Swindells et al. conducted a randomized, open-label, phase 3 noninferiority trial comparing the efficacy and safety of a 1-month regimen of daily rifapentine plus isoniazid with 9 months of isoniazid alone in HIV-infected patients who were living in areas of high tuberculosis prevalence or who had evidence of latent tuberculosis infection. Read the latest NEJM Original Article here.
Q: How many HIV-infected patients who are eligible to receive preventative therapy for tuberculosis are actually treated?
A: Despite extensive high-quality evidence supporting the efficacy of preventive therapy for tuberculosis and recommendations from the World Health Organization and others, the use of such an intervention worldwide has been low. In 2017, fewer than 1 million HIV-infected patients received preventive treatment, with an estimated 30 million eligible. Implementation of tuberculosis preventive therapy in patients with HIV infection has been hampered by operational concerns, poor adherence to long-duration regimens, concern about drug resistance, drug–drug interactions with antiretroviral agents, and skepticism about the effect of this strategy during a time when antiretroviral therapy was being increasingly prescribed.
Q: Is a 1-month regimen of daily rifapentine plus isoniazid noninferior to 9 months of isoniazid alone among HIV-infected persons at high-risk for tuberculosis?
A: In the trial by Swindells et al., the authors found that 1 month of daily rifapentine plus isoniazid was noninferior to daily isoniazid for 9 months for the prevention of tuberculosis in HIV-infected adults and adolescents. The primary end point was the first diagnosis of active tuberculosis, death from tuberculosis, or death from an unknown cause. The primary end point occurred in 32 of 1488 patients (2%) in the 1-month group and in 33 of 1498 (2%) in the 9-month group, with incidence rates of 0.65 and 0.67 per 100 person-years, respectively, for a between-group difference of −0.02 per 100 person-years (95% confidence interval [CI], −0.35 to 0.30).
A: The patients who discontinued treatment because of toxic effects included 16 (1%) in the 1-month group and 25 (2%) in the 9-month group. During the entire follow-up period, serious adverse events occurred in 83 patients (6%) in the 1-month group and in 108 (7%) in the 9-month group (P=0.07). An analysis of the rates of combined grade 3 and 4 serious adverse events and targeted safety events over the entire follow-up period showed that fewer events occurred in the 1-month group than in the 9-month group (2.9 vs. 4.6 events per 100 person-years) (P=0.01). Elevations in liver-enzyme levels of grade 3 or greater and neurologic toxicity were less common in the 1-month group than in the 9-month group (2% vs. 3% and 1% vs. 2%, respectively), whereas neutropenia of grade 3 or higher was more common in the 1-month group (2% vs. 1%).
A: Overall, in the trial by Swindells et al., patient-reported adherence to treatment was 90% or more in each group; treatment was completed in 97% of the patients in the 1-month group and in 90% of those in the 9-month group (P<0.001).