This study aimed to investigate the prevalence of HIV late presentation and advanced HIV disease and to identify the factors associated with HIV late presentation and advanced HIV disease among patients with newly diagnosed HIV/AIDS in the Guangxi Zhuang Autonomous Region, in Southwestern China. Patients with newly diagnosed HIV registered in the HIV surveillance system of Guangxi Centers for Disease Control between January 2012 and December 2016 were included in this study. Of 45,118 newly diagnosed patients, 70.2% had late presentation, and 45.1% had advanced HIV disease. A higher prevalence of late presentation and advanced HIV disease was found in male heterosexuals and female people who use drugs (PWID). Heterosexuals (OR 2.11 [95% CI 1.90–2.34]) and PWID (OR 1.55 [95% CI 1.30–1.84]) had a higher risk of late presentation than men who have sex with men (MSM). Blood testing of the blood receivers (OR 1.75 [95% CI 1.36–2.26]) and diagnosed in hospital (OR 1.74 [95% CI 1.65–1.84]) had an increased risk of late presentation compared to those who diagnosis in voluntary counseling and testing (VCT). Heterosexuals (OR 2.86 [95% CI 2.51–3.27]), PWID (OR 2.23 [95% CI 1.83–2.71]), blood testing of the blood receivers (OR 1.58 [95% CI 1.29–1.94]) and diagnosed in hospital (OR 1.85 [95% CI 1.76–1.94]) were also independent risk factors associated with advanced HIV disease. Older age, lower level of education and being divorced or widowed were also associated with late presentation and advanced HIV disease. Late presentation and advanced HIV disease were very common among patients with newly diagnosed HIV in Guangxi, China during 2012–2016. Targeted programs are urgently required to reduce HIV late diagnosis in Guangxi, especially for male heterosexuals, PWID, and patients with characteristics such as older age, lower level of education, divorced or widowed.

It is a daunting task to eradicate tuberculosis completely in Heng County due to a large transient population, human immunodeficiency virus/tuberculosis coinfection, and latent infection. Thus, a high-precision forecasting model can be used for the prevention and control of tuberculosis. In this study, four models including a basic autoregressive integrated moving average (ARIMA) model, a traditional ARIMA–generalized regression neural network (GRNN) model, a basic GRNN model, and a new ARIMA–GRNN hybrid model were used to fit and predict the incidence of tuberculosis. Parameters including mean absolute error (MAE), mean absolute percentage error (MAPE), and mean square error (MSE) were used to evaluate and compare the performance of these models for fitting historical and prospective data. The new ARIMA–GRNN model had superior fit relative to both the traditional ARIMA–GRNN model and basic ARIMA model when applied to historical data and when used as a predictive model for forecasting incidence during the subsequent 6 months. Our results suggest that the new ARIMA–GRNN model may be more suitable for forecasting the tuberculosis incidence in Heng County than traditional models.

The first-generation integrase inhibitors (INIs) raltegravir (RAL) and elvitegravir (EVG) have shown efficacy against HIV infection, but they have the limitations of once-more daily dosing and extensive cross-resistance. Dolutegravir (DTG, S/GSK1349572), a second-generation drug that overcomes such shortcomings, is under spotlight. The purpose of this study is to review the evidence for DTG use in clinical settings, including its efficacy and safety. PubMed, EMbase, Ovid, Web of Science, Science Direct, and related websites were screened from establishment until July 2013, and scientific meeting proceedings were manually searched. Two reviewers independently screened 118 citations repeatedly to identify randomized controlled trials comparing the efficacy and safety of DTG-based regimen with those of RAL- or elvitegravir-based regimens. Using the selected studies with comparable outcome measures and indications, we performed a meta-analysis based on modified intention-to-treat (mITT), on-treatment (OT), and as-treated (AT) virological outcome data. Independent data extraction and quality assessment were conducted. Four unique studies were included with the use of DTG in antiretroviral therapy-naive patients. In therapy-naive patients, DTG combined with abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) resulted in a significantly better virological outcome with a mITT relative risk (RR)of 1.07 (95 % confidence interval (95 % CI 1.03–1.12). Evidence further supported use of DTG had a better virological suppression in the 50 mg once daily group (mITT RR 1.07; 95 % CI 1.03–1.12) as well as in the sub-analysis in dolutegravir/efavirenz(DTG/EFV) and dolutegravir/raltegravir (DTG/RAL) groups (RR 1.09, 95 % CI 1.03–1.15; RR 1.06, 95 % CI 0.98–1.15, respectively). In the matter of safety of DTG-based regimen, the risk of any event was RR 0.98 (95 % CI 0.94–1.01), the risk of serious adverse events (AEs) was RR 0.84 (95 % CI 0.62–1.15), and the risk of drug-related serious AEs was RR 0.33 (95 % CI 0.13–0.79). In general, DTG 50 mg given once daily combined with an active background drug is a better choice in terms of both efficacy and safety.

The monkeypox outbreak has become a global public health emergency. The lack of valid and safe medicine is a crucial obstacle hindering the extermination of orthopoxvirus infections. The identification of potential inhibitors from natural products, including Traditional Chinese Medicine (TCM), by molecular modeling could expand the arsenal of antiviral chemotherapeutic agents. Monkeypox DNA topoisomerase I (TOP1) is a highly conserved viral DNA repair enzyme with a small size and low homology to human proteins. The protein model of viral DNA TOP1 was obtained by homology modeling. The reliability of the TOP1 model was validated by analyzing its Ramachandran plot and by determining the compatibility of the 3D model with its sequence using the Verify 3D and PROCHECK services. In order to identify potential inhibitors of TOP1, an integrated library of 4103 natural products was screened via Glide docking. Surface Plasmon Resonance (SPR) was further implemented to assay the complex binding affinity. Molecular dynamics simulations (100 ns) were combined with molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) computations to reveal the binding mechanisms of the complex. As a result, three natural compounds were highlighted as potential inhibitors via docking-based virtual screening. Rosmarinic acid, myricitrin, quercitrin, and ofloxacin can bind TOP1 with KD values of 2.16 μM, 3.54 μM, 4.77 μM, and 5.46 μM, respectively, indicating a good inhibitory effect against MPXV. The MM/PBSA calculations revealed that rosmarinic acid had the lowest binding free energy at −16.18 kcal/mol. Myricitrin had a binding free energy of −13.87 kcal/mol, quercitrin had a binding free energy of −9.40 kcal/mol, and ofloxacin had a binding free energy of −9.64 kcal/mol. The outputs (RMSD/RMSF/Rg/SASA) also indicated that the systems were well-behaved towards the complex. The selected compounds formed several key hydrogen bonds with TOP1 residues (TYR274, LYS167, GLY132, LYS133, etc.) via the binding mode analysis. TYR274 was predicted to be a pivotal residue for compound interactions in the binding pocket of TOP1. The results of the enrichment analyses illustrated the potential pharmacological networks of rosmarinic acid. The molecular modeling approach may be acceptable for the identification and design of novel poxvirus inhibitors; however, further studies are warranted to evaluate their therapeutic potential.

In China, the number of newly reported HIV infections in older people is increasing rapidly. However, clear information on the impact of older people on HIV transmission is limited. This study aims to reveal the local HIV transmission patterns, especially how older people affect virus transmission. Subtyping analysis based on available pol sequences obtained from HIV patients revealed that CRF01_AE and CRF08_BC were predominant in patients aged <50 years, whereas CRF01_AE was predominant in older people aged ≥50 years (χ²=29.299, P<0.001). A total of 25 patients (5.2%, 25/484) were identified with recent HIV infection (RHI). Transmission network analysis found 267 genetically linked individuals forming 55 clusters (2 to 63 individuals), including 5 large transmission clusters and 12 transmission clusters containing RHI. Bayesian phylogenetic analysis suggested that transmission events in CRF01_AE and CRF07_BC were centered on older males, while transmission events in CRF08_BC were centered on younger males. Multivariable logistic regression analysis showed that older people were more likely to cluster within networks (AOR=2.303, 95% CI: 1.012-5.241) and that RHI was a significant factor associated with high linkage (AOR=3.468, 95% CI: 1.315-9.146). This study provides molecular evidence that older males play a central role in the local transmission of CRF01_AE and CRF07_BC in Guangxi. Given the current widespread of CRF01_AE and CRF07_BC in Guangxi, there is a need to recommend HIV screening as part of free national medical examinations for older people to improve early detection, timely treatment, and further reduce second-generation transmission.