April C Pettit1,2, Bryan E Shepherd2,3, Timothy R Sterling1,2. 1. Division of Infectious Diseases. 2. Vanderbilt Tuberculosis Center. 3. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Abstract
PURPOSE OF REVIEW: The present review describes recent advances in the treatment of drug-susceptible tuberculosis (DS-TB) among people living with human immunodeficiency virus (PLWH). RECENT FINDINGS: Higher than standard rifampicin doses (>10 mg/kg/day) are well tolerated and have improved sterilizing activity. Standard pyrazinamide doses may result in low drug exposures; modeling reveals that higher doses (>25 mg/kg/day) may be required to reach target levels, although safety is unknown. Four-month fluoroquinolone-containing regimens are not recommended in the 2017 World Health Organization DS-TB treatment guidelines. These guidelines also recommend fixed-dose combination (FDC) therapy over single drug formulations based on patient preference, though FDC is not associated with improved outcomes. Treatment for 6 months is recommended, with an emphasis on expanded antiretroviral therapy (ART) coverage and monitoring for relapse among those not started on ART within 8 weeks of tuberculosis treatment. Directly observed therapy (DOT) is recommended over self-administered therapy, as is daily therapy over intermittent therapy - both are associated with better tuberculosis outcomes. SUMMARY: Current WHO tuberculosis treatment guidelines recommend 6 months of daily tuberculosis treatment for PLWH who have DS-TB, and timely ART initiation. Higher rifampin and pyrazinamide doses may enhance treatment effectiveness, but safety data are needed. DOT and FDC therapy are recommended.
PURPOSE OF REVIEW: The present review describes recent advances in the treatment of drug-susceptible tuberculosis (DS-TB) among people living with human immunodeficiency virus (PLWH). RECENT FINDINGS: Higher than standard rifampicin doses (>10 mg/kg/day) are well tolerated and have improved sterilizing activity. Standard pyrazinamide doses may result in low drug exposures; modeling reveals that higher doses (>25 mg/kg/day) may be required to reach target levels, although safety is unknown. Four-month fluoroquinolone-containing regimens are not recommended in the 2017 World Health Organization DS-TB treatment guidelines. These guidelines also recommend fixed-dose combination (FDC) therapy over single drug formulations based on patient preference, though FDC is not associated with improved outcomes. Treatment for 6 months is recommended, with an emphasis on expanded antiretroviral therapy (ART) coverage and monitoring for relapse among those not started on ART within 8 weeks of tuberculosis treatment. Directly observed therapy (DOT) is recommended over self-administered therapy, as is daily therapy over intermittent therapy - both are associated with better tuberculosis outcomes. SUMMARY: Current WHO tuberculosis treatment guidelines recommend 6 months of daily tuberculosis treatment for PLWH who have DS-TB, and timely ART initiation. Higher rifampin and pyrazinamide doses may enhance treatment effectiveness, but safety data are needed. DOT and FDC therapy are recommended.
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