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Biology subjects

Moore, R. D.

Publications and source records attributed to Moore, R. D..

4 recordsLinked to original sources

Quantifying Exposure of Pacific Salmon and Steelhead to Climate Change in the Fraser River basin

Climate change can affect salmon and steelhead (Oncorhynchus spp.) throughout their anadromous life cycles, yet there have been no assessments of which Canadian populations face the greatest exposure. We developed a framework to quantify relative climate change exposure of salmon and steelhead populations based on the spatial and temporal distribution of different life stages. Exposure was calculated from climate model projections for freshwater and marine climate variables considering unique impact thresholds for each population and life stage. We applied this framework to 60 Conservation Units of Pacific salmon and steelhead in the Fraser River basin, British Columbia. Lake-type sockeye had the highest exposure, driven by elevated stream temperatures during adult freshwater migration and spawning stages and relatively low thermal tolerance of marine stages. Chinook salmon were the next most exposed, while coho, pink, and chum salmon had relatively low exposure. Uniquely, steelhead exposure was driven by high stream temperatures during incubation. Our framework is broadly applicable, and our findings provide critical input for climate change vulnerability assessments and forward-looking resilience planning for Pacific salmon.

ecology↗

Superinfection with intact HIV-1 results in conditional replication of defective proviruses and nonsuppressible viremia in people living with HIV-1

During replication of some RNA viruses, defective particles can spontaneously arise and interfere with wild-type (WT) virus replication. Recently, engineered versions of these defective interfering particles (DIPs) have been proposed as an HIV-1 therapeutic. However, DIPs have yet to be reported in people with HIV-1 (PWH). Here, we find DIPs in PWH who have a rare, polyclonal form of non-suppressible viremia (NSV). While antiretroviral therapy (ART) rapidly reduces viremia to undetectable levels, some individuals experience sustained viremia due to virus production from cell clones harboring intact or defective proviruses. We characterized the source of NSV in two PWH who never reached undetectable viral load despite ART adherence. Remarkably, in each participant, we found a diverse set of defective viral genomes all sharing the same fatal deletions. We found that this paradoxical accumulation of mutations by viruses with fatal defects was driven by superinfection with intact viruses, resulting in mobilization of defective genomes and accumulation of additional mutations during untreated infection. We show that these defective proviruses interfere with WT virus replication, conditionally replicate, and, in one case, have an R0 > 1, enabling in vivo spread. Despite this, clinical outcomes show no evidence of a beneficial effect of these DIPs.

microbiology↗

Class of antiretroviral drugs and anemia risk in the current treatment era

OBJECTIVESAnemia is common among people living with HIV (PLWH) and has been associated with certain, often older, antiretroviral medications. Information on current antiretroviral therapy (ART) and anemia is limited. The objectives were to compare associations between anemia incidence or hemoglobin change with core ART classes in the current ART era.\n\nDESIGNRetrospective cohort study.\n\nSETTINGU.S.-based prospective clinical cohort of PLWH aged 18 and above receiving care at 8 sites between 1/2010-3/2018.\n\nPARTICIPANTS16,505 PLWH were included in this study.\n\nMAIN OUTCOME MEASURESAnemia risk and hemoglobin change were measured for person-time on a protease inhibitor (PI) or an integrase strand transfer inhibitor (INSTI), relative to a non-nucleoside reverse transcriptase inhibitor (NNRTI) reference. We also examined PLWH on multiple core classes. Cox proportional hazards regression analyses were conducted to measure associations between time-updated ART classes and incident anemia or severe anemia. Linear mixed effects models were used to examine relationships between ART classes and hemoglobin change.\n\nRESULTSDuring a median of 4.9 years of follow-up, 1,040 developed anemia and 488 developed severe anemia during. Compared to NNRTI use, INSTI-based regimens were associated with an increased risk of anemia (adjusted hazard ratio [aHR] 1.17, 95% confidence interval [CI] 0.94-1.47) and severe anemia (aHR1.55 95%CI 1.11-2.17), and a decrease in hemoglobin level. Time on multiple core classes was also associated with increased anemia risk (aHR 1.30, 95%CI 1.06-1.60) and severe anemia risk (aHR 1.35, 95%CI 0.99-1.85), while no associations were found for PI use.\n\nCONCLUSIONThese findings suggest INSTI use may increase the risk of anemia. If confirmed, screening for anemia development in users of INSTIs may be beneficial. Further research into underlying mechanisms is warranted.\n\nStrengths and limitations of this studyO_LIThis study utilized a large and geographically diverse population of PLWH in care across the U.S.\nC_LIO_LIThis study leveraged comprehensive clinical data, including information on diagnoses, medication use, laboratory test results, demographic information, and medical history.\nC_LIO_LIThis study investigated associations between specific types of ART core regimens and anemia risk.\nC_LIO_LIThis observational study is subject to residual confounding.\nC_LIO_LIThis study focused on anemia assessed from hemoglobin lab values taken at regular medical care visits without excluding participants with conditions strongly associated with hemoglobin level through non-traditional HIV mechanisms.\nC_LI

epidemiology↗

Association between chronic hepatitis C virus infection and myocardial infarction in people living with HIV in the United States

Hepatitis C virus (HCV) is common among people living with HIV (PLWH). The potential for extrahepatic manifestations of HCV, including myocardial infarction (MI), is a topic of active research. MI is classified into types, predominantly atheroembolic Type 1 MI (T1MI) and supply-demand mismatch Type 2 MI (T2MI). We examined the association between HCV and MI in the CFAR Network of Integrated Clinical Systems (CNICS), a multi-center clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Universal MI definition. We estimated the association between chronic HCV (RNA+) and time to MI adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics and substance use. Among 24,755 PLWH aged [≥]18, there were 336 T1MI and 330 T2MI during a median of 4.2 years of follow-up. HCV was associated with a 68% greater risk of T2MI (adjusted hazard ratio (aHR) 1.68, 95% CI: 1.22, 2.30) but not T1MI (aHR 0.96, 95% CI: 0.63, 1.45). In a cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR 2.26, 95% CI: 1.34, 3.81). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research.

epidemiology↗