Activation of RIG-I signaling in the early stage of Paragonimus proliferus infection causes lung injury via type I immune response in rat.

Paragonimiasis is a common zoonotic parasitic disease. The retinoic acid-inducible gene I (RIG-I) signaling is very important for the host to recognize invading pathogens (especially viruses and bacteria). However, the role of RIG-I signaling in the early stages of P. proliferus infection remains unclear. Therefore, in this study, Sprague-Dawley (SD) rat models with lung damage caused by P. proliferus were established. Experimental methods including Enzyme-linked Immuno Sorbent Assay (ELISA), real-time fluorescent quantitative polymerase chain reaction (PCR), western blotting, and hematoxylin and eosin (HE) staining were used to explore the mechanisms of lung injury caused by P. proliferus. As a result, the expression of the mRNA and proteins of RIG-I signal-related key target molecules, including RIG-I, tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6), interferon regulatory Factor 7 (IRF7), IPS-1, and downstream C-X-C chemokine ligand 10 (CXCL10), were significantly up-regulated immediately after infection, peaked at 3 or 7 days, and showed a downward trend on after 14 days. The levels of pro-inflammatory cytokines interleukin-1 (IL-1), interferon (IFN)-α, -ß, and -γ, which represent type 1 immune response, gradually increased and reached a peak by 14 days, which was consistent with the changes in the degree of inflammatory damage observed under HE staining of lung tissues. In conclusion, RIG-I signaling is activated in the early stage (before 14 days) of P. proliferus infection, it is inferred that the lung injury of the host may be related to the activation of RIG-I like signaling to induce type I immune response.

Carotid Ultrasound Abnormalities of People Living With HIV in Kunming, China: Multiple Correspondence Analysis Approach to Identify Influencing Factors.

BACKGROUND: With the use of antiretroviral therapy (ART), the life expectancy of people living with HIV (PLWH) is gradually increasing, but subclinical atherosclerotic cardiovascular disease is becoming increasingly common in PLWH. METHODS: We obtained data from 326 PLWH. Based on the results of carotid ultrasonography, we divided patients into normal and abnormal carotid ultrasound groups and performed the χ2 test and multiple correspondence analysis (MCA) to determine the influencing factors of abnormal carotid ultrasound. RESULTS: Among the 326 PLWH, the overall abnormality rate of carotid ultrasound was 31.9% (104/326). MCA showed that carotid ultrasound abnormalities were markedly more common in patients with age (non-youth), BMI ≥24.0 kg/m2, hypertension, diabetes, hyperlipidemia, ART treatment ≥5 years, and CD4+T lymphocyte count <200/µL. CONCLUSION: Carotid ultrasound is more likely to be abnormal when PLWH have higher age, BMI ≥24.0 kg/m2, hypertension, diabetes, hyperlipidemia, a longer course of ART, and a low CD4+ T lymphocyte count.

Effects of HIV-related worries on fertility motivation moderated by living children among couples living with HIV: A dyadic analysis.

Introduction: HIV-related worries are a major barrier to achieving fertility goals for couples living with HIV (CLWH). We examined the moderating role of living children in the association between HIV-related worries and fertility motivation in CLWH including happiness, well-being, identity, and continuity. Methods: The data of 322 reproductive-aged CLWH were collected for this cross-sectional study from a referral antiretroviral therapy clinic in Kunming, China between October and December 2020. Intra- and interpersonal mechanisms of association between HIV-related worries and fertility motivation moderated by the number of living children in husband-wife dyads were analyzed by the actor-partner interdependence moderation model. Results: The high-level HIV-related worries of the wives and husbands were associated with the spouses' fertility motivation. Having at least one child helped to ameliorate the negative association between one's own HIV-related worries and fertility motivation. However, there was no evidence of such moderation in the spouse. Conclusion: Whether the CLWH has at least one living child should be taken into account in counseling. Childless families should be counseled on HIV-related worries as those worries have a greater negative effect on fertility motivation than couples who have a child.

Association of Human Leukocyte Antigen Alleles and Hypersensitivity of Efavirenz/Nevirapine in HIV-Infected Chinese Patients.

To examine the association between human leukocyte antigen (HLA) and nevirapine (NVP)- and efavirenz (EFV)-induced cutaneous adverse reactions in human immunodeficiency virus (HIV) patients, we conducted a case-control study at our center consisting of 96 patients. Patients were further assigned based on the occurrence of cutaneous adverse events and the drugs involved. All patients were subjected to next generation sequencing (NGS)-based screening with focus on HLA phenotype, including the presence of HLA-B, HLA-C, and HLA-DRB1. Our data indicated that the HLA-C*01:02:01 allele presence was observed in 47.4% (18/38) of patients in the EFV-hypersensitivity group compared with 18.9% (7/30) in the control group [odds ratio (OR) = 5.837; 95% confidence interval (CI) = 1.727-19.722, p = .005]. In contrast, the occurrence of HLA-DRB1*08:03 was found to be significantly lower in the EFV-hypersensitivity group (4/38, 10.5%) compared with the corresponding control group (12/37, 32.4%) (OR = 0.148; 95% CI = 0.035-0.625, p = .009). In addition, the HLA-DRB1*04:05:01 antigen was expressed more frequently in the NVP-hypersensitivity group (23.8%, 5/21) compared with the control group (10.8%, 4/37) (OR = 7; 95% CI = 1.265-38.793, p = .026). Our data not only revealed a significant association between HLA-C*01:02:01 and EFV-induced cutaneous adverse reactions but may also shed light on defining the treatment for Chinese HIV patients.

Cytomegalovirus viremia is associated with poor outcomes in AIDS patients with disseminated nontuberculous mycobacterial disease.

Both cytomegalovirus (CMV) viremia and disseminated nontuberculous mycobacterial (NTM) disease are common opportunistic infections in AIDS patients. Whether concurrent CMV viremia is associated with mortality in patients with AIDS and disseminated NTM disease is unknown. Subjects were patients with AIDS and disseminated NTM disease seen at a single center from January 2015 to April 2021. Data were retrospectively collected. Differences in demographics and clinical characteristics and hospitalization survival rates were compared between patients with disseminated NTM and with CMV viremia or not. Subjects were 113 AIDS patients with disseminated NTM who were seen at this Hospital from January 2015 to April 2021. Twenty-six of the patients had CMV viremia and 87 did not. The median age was 36 years (interquartile range [IQR] 29-42) and 108 patients were male (96%). The median CD4 count was 7 cells/µL (IQR 3-17). The median plasma CMV viral load was 9,245 IU/mL (IQR 3147-45725). The serum albumin of patients with CMV viremia was significantly lower than that of patients without CMV viremia (P = 0.03). Compared to patients without CMV viremia (81.6%), patients with CMV viremia had a significantly poorer prognosis (P = 0.01). Cox regression analysis indicated that the risk of a poor prognosis in patients with CMV viremia was 4.7 times higher than that in patients without CMV viremia (P = 0.003), and patients with CD8 more than 250/µL had a better prognosis (P = 0.02). CMV viremia increases the risk of a poor prognosis in patients with AIDS and a disseminated NTM infection. A routine CMV DNA test should be performed on patients with AIDS and disseminated NTM disease in order to reduce the risk of death.

Prevalence and risk factors for anogenital HPV infection and neoplasia among women living with HIV in China.

OBJECTIVES: To explore the prevalence and risk factors of anogenital human papillomavirus (HPV) infection and neoplasia among women living with HIV (WLHIV) in China. METHODS: A cross-sectional survey was conducted from 2019 to 2020, 409 WLHIV aged 18 years and older were recruited from an HIV treatment clinic in Yunnan, China. Cervical and anal samples were collected for HPV testing of 15 HPV genotypes and cytological interpretation. Women positive for cervical HPV or cytological abnormalities were recalled for colposcopy examination and biopsy when necessary. Prevalence of anogenital HPV infection and neoplasia were compared by logistic regression. RESULTS: HPV prevalence was 34.2% (140/409) for cervical and 34.7% (142/409) for anal (high-risk HPV being 30.6% (125/409) and 30.3% (124/409), respectively). The most frequent genotypes were HPV-52, HPV-16 and HPV-58 in the cervix, HPV-52, HPV-53 and HPV-39 in the anus, with strong correlation between cervical and anal positivity, both overall and at a type-specific level. Cervical HPV was most associated with short duration of combination antiretroviral therapies (cART) (≤2 vs >2 years, adjusted OR (aOR)=2.25, 95% CI: 1.22 to 4.12) and high initial HIV viral load (≥1000 vs <1000 copies/mL, aOR=1.98, 95% CI: 1.10 to 3.58). Anal HPV was most associated with low nadir CD4 count (<200 vs ≥200 cells/µL, aOR=1.80, 95% CI: 1.01 to 3.22) and low current CD4 count (<350 vs ≥500 cells/µL, aOR=2.06, 95% CI: 1.00 to 4.36). CIN2+ prevalence was 4.6% and associated with low nadir CD4 count (aOR=4.63, 95% CI: 1.24 to 17.25). CONCLUSIONS: Cervical and anal HPV were strongly correlated and, together with associated neoplasia, were highly prevalent among WLHIV in China. Early initiation of cART to avoid severe immunodeficiency should decrease anogenital HPV prevalence and related cancer burden among WLHIV. Incorporating anogenital cancer prevention services into HIV/AIDS care is warranted.

Tolerability and Adherence of Antiretroviral Regimens Containing Long-Acting Fusion Inhibitor Albuvirtide for HIV Post-Exposure Prophylaxis: A Cohort Study in China.

INTRODUCTION: There have been no prospective clinical studies investigating adherence and tolerability of HIV post-exposure prophylaxis (PEP) in China. Tolerability, adherence, and transmitted drug resistance are concerns, especially when single-tablet regimen (STR) usage is low. The present study aimed to explore the safety, tolerability, and adherence of regimens containing albuvirtide (ABT) compared with recommended non-STR antiretrovirals for HIV PEP. METHODS: This was a prospective, open-label, multicenter cohort study. The subjects were stratified into 3 groups based on their preference: ABT + Dolutegravir (DTG) (Group 1), ABT + Tenofovir disoproxil fumarate (TDF) + Lamivudine (3TC) (Group 2), and DTG + TDF + 3TC (Group 3). All enrolled subjects received PEP within 72 h after exposure and continued for 28 days, and were followed-up for 12 weeks. RESULTS: A total of 330 participants were enrolled in the three groups. Most participants were male (87.2%). Sexual contact was the most frequent mode of exposure (91.9%). The average time from exposure to treatment was 26.8 ± 19.5 h. There were no statistically significant differences between the three study groups with respect to completion of oral medication at 28 days. The 28-day completion rate was shown to be significantly higher with ABT versus oral (88.9% vs. 64.0%; p < 0.0001), and adherence with ABT was 94.4% compared to 75.7% with oral PEP (p < 0.0001). Subjects in ABT-containing Group 1 exhibited higher adherence than those in Group 3 (87.3% vs. 72.9%; p < 0.05). None of the participants reported serious adverse drug reactions which led to withdrawal from the study. All the drug regimens were found to be safe and well tolerated. No HIV incident case was observed during the study period. CONCLUSIONS: ABT-containing regimens (ABT + DTG or ABT + TDF + 3TC) offer a good option for HIV PEP due to higher completion rates and adherence than the DTG + TDF + 3TC regimen. The overall safety was comparable and acceptable among the three groups. REGISTRATION: The study was registered in Chinese Clinical Trial Registry with registration number (ChiCTR1900022881, http://www.chictr.org.cn/showprojen.aspx?proj=37395 ).

The predictive role of CD4+ cell count and CD4/CD8 ratio in immune reconstitution outcome among HIV/AIDS patients receiving antiretroviral therapy: an eight-year observation in China.

BACKGROUND: The immune reconstitution after initiation of highly active antiretroviral therapy (HAART) among HIV-infected individuals substantially affects patients' prognosis. However, the dynamic characteristics and predictors of reconstitution outcome remain unclear. METHODS: In this study, the HIV/AIDS patients with sustained virological suppression (viral load < 50 copies/ml) after HAART were enrolled. The patients were subgrouped into immunological non-responders (INRs) (< 200 cells/µl), immunological inadequate responders (IIRs) (200 ~ 500 cells/µl) and immunological responders (IRs) (> 500 cells/µl) according to the CD4 cell count after two-year HAART. The immune reconstitution data based on the CD4+ and CD8+ cell counts with 8-year follow-up were collected for analysis. RESULTS: The CD4+ cell counts in the immunological responders (IRs) were significantly higher than in the immunological non-responders (INRs) and immunological inadequate responders (IIRs) (P <  0.001). The overall CD4+ cell count and CD4/CD8 ratio in the IRs increased faster than the IIRs and INRs. The CD4+ cell count growth at 0.5 year and 1 year after HAART in the IRs was significantly higher than the IIRs and INRs. The ROC curve demonstrated that 1 year CD4+ cell count had the highest predictive value, with the best cut-off value of 188 cells/µl, the predictive sensitivity was 81.0%, the predictive specificity was 85.2%, false positive rate was 14.8%, false negative rate was 19.0%, positive predictive value (IR) was 63.0%, negative predictive value (INR) was 93.5%. CONCLUSIONS: Taken together, our findings suggest that early initiation of HAART can reduce the immune reconstitution failure. The combination of baseline CD4+ cell count and baseline CD4/CD8 ratio may serve as a valid predictor of immune reconstitution prognosis after HAART.

The Double Burdens of Mental Health Among AIDS Patients With Fully Successful Immune Restoration: A Cross-Sectional Study of Anxiety and Depression in China.

Background: Anxiety and depression continue to be significant comorbidities for people with HIV infection. We investigated the prevalence of and factors associated with anxiety and depression among adult HIV-infected patients across China. Methods: In this cross-sectional study, we described clinical and psychosocial variables related to depression and anxiety in 4103 HIV-infected persons. Doctors assessed anxiety and depression by asking patients whether they had experienced anxiety or depression in the prior month. Patients also self-administered the Hospital Anxiety and Depression (HAD) scale; those with score ≥8 on HAD-A/D were considered to be at high risk of anxiety or depression. Results: Associations between socio-demographic, psychosocial, and ART-related clinical factors and risk of depression or anxiety were investigated using multivariable logistic regression. Among patients assessed between 9/2014 and 11/2015, 27.4% had symptoms of anxiety, 32.9% had symptoms of depression, and 19.0% had both. Recentness of HIV diagnoses (P = 0.046) was associated with elevated odds of anxiety. Older age (P = 0.004), higher educational attainment (P < 0.001), employment (P = 0.001), support from family / friends (P < 0.001), and sleep disturbance (P < 0.001), and number of ART regimen switches (P = 0.046) were associated with risk of depression, while neither sex nor transmission route showed any associations. There were no significant associations with HIV-specific clinical factors including current CD4+ T cell count and current viral load. Conclusions: Prevalence of symptoms of anxiety and depression is high in this cohort of treatment-experienced HIV patients. Psychological and social-demographic factors, rather than HIV disease status, were associated with risk of depression and anxiety. This finding highlights the need to deliver interventions to address the mental health issues affecting HIV-infected persons with fully successful immune restoration across China.

Burden of sleep disturbances and associated risk factors: A cross-sectional survey among HIV-infected persons on antiretroviral therapy across China.

This study evaluated the prevalence and factors associated with sleep disturbance in a large cohort of HIV-infected patients across China. A cross-sectional study was conducted among HIV-infected patients on antiretroviral therapy at 20 AIDS clinics. The Pittsburgh Sleep Quality Index was self-administered by subjects. Socio-demographic characteristics, medical history and HIV-related clinical data were collected. 4103 patients had complete data for analysis. Sleep disturbances were observed in 43.1% of patients. Associated factors in multivariable analysis included psychological factors: anxiety (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.44-4.00; P < 0.001), depression (OR, 2.09; 95% CI, 1.70-2.57; P < 0.001), and both anxiety and depression (OR, 5.90; 95% CI, 4.86-7.16; P < 0.001); sociodemographic factors: MSM (OR, 1.26; 95% CI, 1.04-1.52; P = 0.018), being single (OR, 1.45; 95%CI 1.21-1.74; P < 0.001), higher education (OR, 1.25; 95% CI, 1.03-1.53; P = 0.025); and clinical factors: suboptimal adherence (OR,1.51; 95% CI,1.23-1.85; P < 0.001), regimen-switching (OR, 1.94; 95% CI, 1.12-3.35; P = 0.018), and antidepressant use (OR, 1.98; 95% CI, 1.47-2.67; P = 0.044). Prevalence of sleep disturbance is high in this large Chinese cohort. Associated factors appear related to psychological and social-demographic factors. Health workers may consider routinely assessing sleep disturbances among HIV-infected patients, especially in the first three months after HIV diagnosis, and referring for mental health services, which may positively impact adherence to treatment.

Selective extraction of functional components derived from herb in plasma by using a molecularly imprinted polymer based on 2,2-bis(hydroxymethyl)butanol trimethacrylate.

To make molecularly imprinted polymer (MIP) solid-phase extraction (SPE) capable of direct clean-up of aqueous biological samples, an anti-quercetin MIP with evident hydrophobic matrix was synthesized using acrylamide (AA) as the functional monomer and 2,2-bis(hydroxymethyl)butanol trimethacrylate (TRIM) as the crosslinker. The affinity and selectivity were evaluated by liquid chromatography, and the binding sites and the dissolution constants were measured by frontal chromatography. Compared with the AA-co-ethyleneglycol dimethacrylate (EDMA) MIP, the anti-quercetin AA-co-TRIM MIP exhibited stronger binding and possessed improved column efficacy. A linear plot of the peak area versus sample size (in the range of 0.4-2.2 microg) was obtained, which made it promising for the MIP columns to be directly used for analysis. Before MIP-SPE of the sample of plasma, several washing solvents were tested and it was shown that the careful choice of the right washing solvent is the key step to successful sample extraction. The anti-quercetin AA-co-TRIM polymer selectively extracted quercetin, the effective component in the plasma of rats fed the hydrolyzed extract of Gingko biloba L. The recovery (67%) for MIP-SPE was calculated using spiked plasma. The results of the present work showed that the properties of MIP could be improved by modifying the polymerization and that MIP-SPE could be used for direct clean-up of biological samples for the analysis of functional components in vivo originating from an extract of medicinal herbs.