Hypomorphic CARD9 deficiency caused by p.Y91H results in adult-onset disease with variable penetrance and expressivity. Our findings establish the CARD9/RASGRF1/ERK/GM-CSF axis as critical to the pathophysiology of sCNSc.
Objectives: Fifteen years after the roll-out of antiretroviral treatment (ART) in China, there is limited information available on transmitted HIV drug resistance (TDR). This study aimed to characterize the epidemiology of TDR in China. Design: We conducted a prospective cross-sectional observational study. Methods: We analyzed the demographic, clinical, and virological data of individuals with newly diagnosed HIV infection using data from the Beijing HIV laboratory network collected between 2001 and 2017. We did population-based sequencing of the pol gene on plasma specimens and identified TDR mutations using the WHO list for surveillance of TDR mutations. Results: Data on TDR were available for 91% of the 10 115 individuals with newly diagnosed HIV infection tested, of whom 19.2% were from rural areas. The overall prevalence of TDR was 4.1% [95% confidence interval (CI): 3.7–4.5%], with a declining trend over the period 2001–2017. In the multivariable analysis, the risk of TDR differed significantly according to sex [odds ratio (OR) for women vs. men: 0.41, 95% CI: 0.22–0.69, P = 0.002]; infection type (OR for CRF07_BC vs. CRF01_AE: 0.24, 95% CI: 0.16–0.36, P < 0.001); and sampling period (OR for 2009–2012 vs. 2001–2008: 0.57, 95% CI: 0.41–0.79; P = 0.01), and was significantly higher among individuals from Hebei province than in those from Beijing (OR: 1.43, 95% CI: 1.05–1.96; P = 0.02). Conclusion: In China, the prevalence of TDR among individuals with newly diagnosed HIV infection is relatively low. Trends in TDR should be assessed in other countries with a high TDR burden.
Background Beijing is a national and international hub potentially containing a broad diversity of HIV variants. Previous studies on molecular epidemiology of HIV in Beijing pooled together samples from residents and non-residents. Pooling residents and non-residents has potentially introduced bias and undermined a good assessment and the intervention among the autochthonous population. Here, we aimed to define HIV subtype diversity and investigate the TDR in Beijing residents exclusively. Methods We analyzed the demographic, clinical, and virological data collected between 2001 and 2016 from residents in Beijing. A population-based sequencing of the HIV pol gene was carried out using plasma specimens. Phylogenetic analysis was performed in order to classify sequences into their corresponding subtypes using an automated subtyping tool, the Context-Based Modeling for Expeditious Typing (COMET). Furthermore, the drug resistance mutations were determined using the World Health Organization list for surveillance of TDR mutations. Results Data on TDR were available for 92% of 2,315 individuals with HIV infection, of whom 7.1% were women. The bioinformatic analysis of HIV strains from this study revealed that a combined 17 subtypes were circulating in Beijing, China between 2001 and 2016. The most common ones were CRF01_AE, CRF07_BC, and subtype B in Beijing during this period. The overall prevalence of TDR was 4.5% (95% confidence intervals[CI]: 3.6%-5.4%), with a declining trend over the period of spanning 2001 through 2016. In-depth
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