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- Howe, Anita Y. M., et al.
(författare)
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Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals
- 2022
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Ingår i: JHEP Reports. - : Elsevier. - 2589-5559. ; 4:5
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure.Methods: SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated. Results: The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in >-1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing >-2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4.Conclusions: Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized.Lay summary: Although direct-acting antiviral medications effectively cure hepatitis C in most patients, sometimes treatment selects for resistant viruses, causing antiviral drugs to be either ineffective or only partially effective. Multidrug resistance is common in patients for whom DAA treatment fails. Older patients and patients with advanced liver diseases are more likely to select drug-resistant viruses. Collective efforts from international communities and governments are needed to develop an optimal approach to managing drug resistance and preventing the transmission of resistant viruses.
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- Zhou, Huimin, et al.
(författare)
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Relative importance of climatic variables, soil properties and plant traits to spatial variability in net CO2 exchange across global forests and grasslands
- 2021
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Ingår i: Agricultural and Forest Meteorology. - : Elsevier BV. - 0168-1923. ; 307
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Tidskriftsartikel (refereegranskat)abstract
- Compared to the well-known drivers of spatial variability in gross primary productivity (GPP), the relative importance of climatic variables, soil properties and plant traits to the spatial variability in net ecosystem exchange of CO2 between terrestrial ecosystem and atmosphere (NEE) is poorly understood. We used principal component regression to analyze data from 147 eddy flux sites to disentangle effects of climatic variables, soil properties and plant traits on the spatial variation in annual NEE and its components (GPP and ecosystem respiration (RE)) across global forests and grasslands. Our results showed that the largest unique contribution (proportion of variance only explained by one class of variables) to NEE variance came from climatic variables for forests (24%-30%) and soil properties for grasslands (41%-54%). Specifically, mean annual precipitation and potential evapotranspiration were the most important climatic variables driving forest NEE, whereas available soil water capacity, clay content and cation exchange capacity mainly influenced grassland NEE. Plant traits showed a small unique contribution to NEE in both forests and grasslands. However, leaf phosphorus content strongly interacted with soil total nitrogen density and clay content, and these combined factors represented a major contribution for grassland NEE. For GPP and RE, the majority of spatial variance was attributed to the common contribution of climate, soil and plant traits (50% - 62%, proportion of variance explained by more than one class of variables), rather than their unique contributions. Interestingly, those factors with only minor influences on GPP and RE variability (e.g., soil properties) have significant contributions to the spatial variability in NEE. Such emerging factors and the interactions between climatic variables, soil properties and plant traits are not well represented in current terrestrial biosphere models, which should be considered in future model improvement to accurately predict the spatial pattern of carbon cycling across forests and grasslands globally.
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