Drivers and trajectories of resistance to new first-line drug regimens for tuberculosis

Open Forum Infectious Diseases
Sourya ShresthaDavid W Dowdy

Abstract

New first-line drug regimens for treatment of tuberculosis (TB) are in clinical trials: emergence of resistance is a key concern. Because population-level data on resistance cannot be collected in advance, epidemiological models are important tools for understanding the drivers and dynamics of resistance before novel drug regimens are launched. We developed a transmission model of TB after launch of a new drug regimen, defining drug-resistant TB (DR-TB) as resistance to the new regimen. The model is characterized by (1) the probability of acquiring resistance during treatment, (2) the transmission fitness of DR-TB relative to drug-susceptible TB (DS-TB), and (3) the probability of treatment success for DR-TB versus DS-TB. We evaluate the effect of each factor on future DR-TB prevalence, defined as the proportion of incident TB that is drug-resistant. Probability of acquired resistance was the strongest predictor of the DR-TB proportion in the first 5 years after the launch of a new drug regimen. Over a longer term, however, the DR-TB proportion was driven by the resistant population's transmission fitness and treatment success rates. Regardless of uncertainty in acquisition probability and transmission fitness, high levels (>10...Continue Reading

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Sep 27, 2015·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Gwenan M KnightTed Cohen
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Apr 25, 2019·BMC Medicine·Anna Maria NiewiadomskaCecile Viboud

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