Corrigendum: Six-month humoral immune response to inactivated COVID-19 vaccine among people living with HIV.

[This corrects the article DOI: 10.3389/fimmu.2022.988304.].

Pentacyclic triterpenes as bioactive compounds isolated from Mauritia flexuosa L. f. acting against the Alzheimer's disease.

Alzheimer's disease is a significant concern due to its high prevalence and the limitations of current treatments. In our research, we investigated Mauritia flexuosa, a medicinal plant traditionally used for headaches, to identify active compounds with potential anti-Alzheimer's effects. Three pentacyclic triterpenes were isolated through column chromatography and characterised from the dichloromethane/methanol extract from Mauritia flexuosa (DCMEMf), with (3ß)-3-hydroxy-11-oxours-12-en-28-oic acid (3) showing the highest in vitro activity in the HMC3 and SVG p12 cell lines. Compound 3 inhibited the pharmacological targets NF-κB, PGE2, IDO1, and EGFR with IC50 values of 9.83, 3.86, 1.63 µM, and 49.57 nM, respectively, attributed to a hydroxyl group at the C-3 position of its structure. These findings suggest the potential of these compounds in treating neurological diseases, including headaches, and offer promising prospects for the development of new therapies against Alzheimer's.

People living with HIV with the Omicron variant infection have milder COVID-19 symptoms: results from a cross-sectional study.

BACKGROUND: China braces for coronavirus disease 2019 (COVID-19) surge after adjusting the "zero COVID" strategy. We aimed to evaluate and compare the prevalence of clinical symptoms of the Omicron variant infection among people living with HIV (PLWH) and HIV-free people. METHODS: A cross-sectional study was conducted in Wuchang District, Wuhan, Hubei Province, in December 2022 by a self-administered online survey during the Omicron wave. Participants aged ≥ 18 years with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis were recruited. PLWH managed by the local healthcare system were recruited, while HIV-free people were recruited by sending out online surveys through WeChat. We compared the prevalence of clinical symptoms of COVID-19 between PLWH and HIV-free people, and factors associated with symptom occurrence among PLWH were accessed. RESULTS: Total, 687 PLWH and 1222 HIV-free people were enrolled. After adjusting sex, age, body mass index, comorbidities and COVID-19 vaccination status, the prevalences of all symptoms, including higher degree and long duration of fever (aOR 0.51, 95%CI 0·42 - 0·61; aOR 0.52, 95%CI 0·43 - 0·63), were significantly lower among PLWH than among HIV-free people. Among PLWH, CD4+ T lymphocyte count (CD4 count) between 350 ~ 499 cells/µL and detectable HIV viral load (HIV-VL) were associated with significantly decreased risks of fever (aOR 0·63, 95%CI 0·40 - 0·97; aOR 0·56, 95%CI 0·33 - 0·94), headache (aOR 0·61, 95%CI 0·41 - 0·91; aOR 0·55, 95%CI 0·34 - 0·92) and muscle soreness (aOR 0·57, 95%CI 0·39 - 0·84; aOR 0·57, 95%CI 0·39 - 0·84). No apparent association between the symptoms prevalence and three/four doses of inactivated COVID-19 vaccination among PLWH was observed; both males and older age were associated with significantly decreased risks of nasal congestion/runny nose (aOR 0·52, 95%CI 0·32 - 0·82; aOR 0·97, 95%CI 0·96 - 0·99) and headache (aOR 0·58, 95%CI 0·36 - 0·92; aOR 0·96, 95%CI 0·95 - 0·98); older age was associated with significantly decreased risks of higher degree of fever (aOR 0·97, 95%CI 0·95 - 0·98). CONCLUSIONS: PLWH have significantly milder symptoms of the Omicron variant infection than HIV-free people. PLWH who are male, older, have low CD4 count, and detectable HIV-VL have reduced occurrence of COVID-19 symptoms. However, continuous monitoring should be conducted among PLWH during the COVID-19 pandemic.

Different concentrations of hyaluronic acid eye drops for dry eye syndrome: a systematic review and Meta-analysis.

AIM: To compare high or low concentration of hyaluronic acid eye drops (HY) for dry eye syndromes (DES). METHODS: Randomized controlled trials (RCTs) comparing various concentrations of HY were searched in PubMed, Embase, Web of Science, Cochrane, SinoMed, CNKI, Wanfang Database, CQVIP, and Chinese journals databases between inception and July 2023. Pooled standardized mean differences (SMD) or weighted mean difference (WMD) with 95% confidence intervals (CI) from RCTs evaluating Schirmer's I test (SIT), corneal fluorescein staining score (CFS), tear breakup time (TBUT), DES score (DESS), and Ocular Surface Disease Index (OSDI) were calculated. Sensitivity analysis, Egger's test and Meta-regression analysis were performed for all indicators. RESULTS: We conducted a Meta-analysis of 10 RCTs that met the inclusion criteria, involving 1796 cases. High-concentrations group significantly improved the outcome of CFS according to random effects modelling (SMD, -3.37; 95%CI, -5.25 to -1.48; P=0.0005). The rest of the results were not statistically significant, including indicators such as SIT, TBUT, DESS and OSDI. CONCLUSION: For dry eyes with positive corneal staining, a high concentration of HY is recommended, whereas in other cases, a high concentration of HY does not offer a more pronounced advantage over a low concentration of HY in the treatment of dry eyes.

Life-threatening gastrointestinal bleeding caused by cytomegalovirus-induced duodenal ulcer in a patient with AIDS: A case report.

Background: The reasons for gastrointestinal bleeding among patients with acquired immune deficiency syndrome (AIDS) were complex. Here we present an unusual case of life-threatening gastrointestinal bleeding caused by a cytomegalovirus-induced duodenal ulcer in an AIDS patient. Case presentation: A 31-year-old male with AIDS was admitted on July 18, 2023, complaining of abdominal pain for 38 days and intermittent hematochezia for 12 days. During his hospitalization, gastrointestinal endoscopy attributed gastrointestinal bleeding to a giant duodenal ulcer. Furthermore, cytomegalovirus(CMV) infection was confirmed as the reason for the ulcer through metagenomic next-generation sequencing (mNGs), hematoxylin-eosin(HE) staining, and immunohistochemistry (IHC) staining for the biopsy tissue. The patient's gastrointestinal bleeding was stopped by interventional embolization. Following a 4-week course of anti-CMV treatment, the giant duodenal ulcer was cured. Conclusions: For AIDS patients with gastrointestinal bleeding, the CMV-induced gastrointestinal ulcer should be considered. Comprehensive mothods (mNGs, HE staining and IHC staining for biopsy tissue) were benefit for confirmed diagnosis. Beside anti-CMV treatment, the interventional embolization is a choice for hemostasis.

Microbiomes detected by cerebrospinal fluid metagenomic next-generation sequencing among patients with and without HIV with suspected central nervous system infection.

BACKGROUND: Opportunistic infections in the central nervous system (CNS) can be a serious threat to people living with HIV. Early aetiological diagnosis and targeted treatment are crucial but difficult. Metagenomic next-generation sequencing (mNGS) has significant advantages over traditional detection methods. However, differences in the cerebrospinal fluid (CSF) microbiome profiles of patients living with and without HIV with suspected CNS infections using mNGS and conventional testing methods have not yet been adequately evaluated. METHODS: We conducted a retrospective cohort study in the first hospital of Changsha between January 2019 and June 2022 to investigate the microbiomes detected using mNGS of the CSF of patients living with and without HIV with suspected CNS infections. The pathogens causing CNS infections were concurrently identified using both mNGS and traditional detection methods. The spectrum of pathogens identified was compared between the two groups. RESULTS: Overall, 173 patients (140 with and 33 without HIV) with suspected CNS infection were enrolled in our study. In total, 106 (75.7%) patients with and 16 (48.5%) patients without HIV tested positive with mNGS (p = 0.002). Among the enrolled patients, 71 (50.7%) with HIV and five (15.2%) without HIV tested positive for two or more pathogens (p < 0.001). Patients with HIV had significantly higher proportions of fungus (20.7% vs. 3.0%, p = 0.016) and DNA virus (59.3% vs. 21.2%, p < 0.001) than those without HIV. Epstein-Barr virus (33.6%) was the most commonly identified potential pathogen in the CSF of patients living with HIV using mNGS, followed by cytomegalovirus (20.7%) and torque teno virus (13.8%). The top three causative pathogens identified in patients without HIV were Streptococcus (18.2%), Epstein-Barr virus (12.1%), and Mycobacterium tuberculosis (9.1%). In total, 113 patients living with HIV were diagnosed as having CNS infections. The rate of pathogen detection in people living with HIV with a CNS infection was significantly higher with mNGS than with conventional methods (93.8% vs. 15.0%, p < 0.001). CONCLUSION: CSF microbiome profiles differ between patients living with and without HIV with suspected CNS infection. mNGS is a powerful tool for the diagnosis of CNS infection among people living with HIV, especially in those with mixed infections.

Patterns and Prognosis of Local Recurrence of Nasopharyngeal Carcinoma after Intensity-modulated Radiotherapy.

Objective: To investigate the patterns of local failure and prognosis in patients with locally recurrent nasopharyngeal carcinoma (rNPC) after primary intensity-modulated radiotherapy (IMRT). Methods: The data of 298 patients with locally rNPC after IMRT were retrospectively analyzed. Magnetic resonance images of the initial and recurrent tumors were reviewed and, for patients with extra-nasopharyngeal local recurrence, the gross tumor volume of local recurrence was transferred to the original IMRT plan for dosimetry analysis. Significant prognostic factors for overall survival (OS) were selected by multivariate Cox regression analysis. Results: The commonest recurrence sites were the nasopharynx (93%, 277/298) and skull base (53.7%, 160/298). Of the 21 patients with extra-nasopharyngeal recurrence (19 cases valid), 12 had in-field failures, 4 had marginal failures, and 3 had out-field failures. The ethmoid sinus (57.1%, 4/7) and nasal cavity (28.6%, 2/7) were the most frequent sites of marginal and out-field failures. After median follow-up of 37 months, the 3-year and estimated 5-year OS rates were 57.3% and 41.7%, respectively. Multivariate analysis showed that age, recurrence interval, plasma Epstein-Barr virus (EBV) DNA level, and recurrent T stage were independent prognostic factors for OS. Conclusions: Local failure after IMRT occurs most commonly in the nasopharynx and skull base. In patients with extra-nasopharyngeal recurrence, in-field failure remains the main failure pattern, and marginal and out-field failures mainly occur in the ethmoid sinus and nasal cavity. Elder age, shorter recurrence interval, detectable plasma EBV DNA, and advanced recurrent T stage are negative predictors of OS in patients with rNPC.

Mangiferin alleviates diabetic pulmonary fibrosis in mice via inhibiting endothelial-mesenchymal transition through AMPK/FoxO3/SIRT3 axis.

Diabetes mellitus results in numerous complications. Diabetic pulmonary fibrosis (DPF), a late pulmonary complication of diabetes, has not attracted as much attention as diabetic nephropathy and cardiomyopathy. Mangiferin (MF) is a natural small molecular compound that exhibits a variety of pharmacological effects including anti-inflammatory, anti-cancer, anti-diabetes, and anti-fibrosis effects. In this study, we investigated whether long-term diabetes shock induces DPF, and explored whether MF had a protective effect against DPF. We first examined the lung tissues and sections of 20 diabetic patients obtained from discarded lung surgical resection specimens and found that pulmonary fibrosis mainly accumulated around the pulmonary vessels, accompanied by significantly enhanced endothelial-mesenchymal transition (EndMT). We established a mouse model of DPF by STZ injections. Ten days after the final STZ injection, the mice were administered MF (20, 60 mg/kg, i.g.) every 3 days for 4 weeks, and kept feeding until 16 weeks and euthanized. We showed that pulmonary fibrotic lesions were developed in the diabetic mice, which began around the pulmonary vessels, while MF administration did not affect long-term blood glucose levels, but dose-dependently alleviated diabetes-induced pulmonary fibrosis. In human umbilical vein endothelial cells (HUVECs), exposure to high glucose (33.3 mM) induced EndMT, which was dose-dependently inhibited by treatment with MF (10, 50 µM). Furthermore, MF treatment promoted SIRT3 expression in high glucose-exposed HUVECs by directly binding to AMPK to enhance the activity of FoxO3, which finally reversed diabetes-induced EndMT. We conclude that MF attenuates DPF by inhibiting EndMT through the AMPK/FoxO3/SIRT3 axis. MF could be a potential candidate for the early prevention and treatment of DPF.

Hydroxycitric Acid Alleviated Lung Ischemia-Reperfusion Injury by Inhibiting Oxidative Stress and Ferroptosis through the Hif-1α Pathway.

Lung ischemia-reperfusion injury (LIRI) is a prevalent occurrence in various pulmonary diseases and surgical procedures, including lung resections and transplantation. LIRI can result in systemic hypoxemia and multi-organ failure. Hydroxycitric acid (HCA), the primary acid present in the peel of Garcinia cambogia, exhibits anti-inflammatory, antioxidant, and anticancer properties. However, the effects of HCA on LIRI remain unknown. To investigate the impact of HCA on LIRI in mice, the mice were randomly divided into four groups: the control group, the I/R model group, and the I/R + low- or high-dose HCA groups. Human umbilical vein endothelial cells (HUVECs) were subjected to hypoxia for 12 h followed by reoxygenation for 6 h to simulate in vitro LIRI. The results demonstrated that administration of HCA effectively attenuated lung injury, inflammation, and edema induced by ischemia reperfusion. Moreover, HCA treatment significantly reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels while decreasing iron content and increasing superoxide dismutase (SOD) levels after ischemia-reperfusion insult. Mechanistically, HCA administration significantly inhibited Hif-1α and HO-1 upregulation both in vivo and in vitro. We found that HCA could also alleviate endothelial barrier damage in H/R-induced HUVECs in a concentration-dependent manner. In addition, overexpression of Hif-1α counteracted HCA-mediated inhibition of H/R-induced endothelial cell ferroptosis. In summary, these results indicate that HCA alleviated LIRI by inhibiting oxidative stress and ferroptosis through the Hif-1α pathway.

[Regional CT value in prediction of proximal femoral fracture].

OBJECTIVE: To investigate CT values of cancellous bone in femoral neck in adults over 60 years with proximal femoral fractures. METHODS: From January 2020 to December 2020, a retrospective analysis was performed on 280 subjects aged 60 years or older who underwent bilateral hip CT examination, including 85 males and 195 females, 120 on the left side and 160 on the right side, aged 75 (66, 82) years old. One hundred thirty-six patients with proximal femoral fractures were included in study group and 144 patients without fractures were included in control group. GEOptima CT was used to scan and reconstruct horizontal, coronal and sagittal layers of proximal femur. CT values of cancellous bone in femoral neck were measured and compared between two groups. The relationship between CT values of cancellous bone of femoral neck and proximal femoral fracture was analyzed statistically. RESULTS: In terms of age, fracture group aged 79(73.3, 85.0) years old, non-fracture group aged 69.5 (64.0, 78.8) years old, and had significant difference in age between two groups (P<0.05). In terms of CT value, regional CT value in fracture group was 8.62(-3.62, 27.15) HU, which was lower than that in non-fracture group 34.31(-5.93, 71.74) HU(P<0.05). CT value on coronal view in fracture group was -8.48(-30.96, 17.46) HU, which was lower than that in non-fracture group 40.49(5.55, 80.71) HU (P<0.05). CT value on sagittal view in fracture group was -31.28(-54.91, -5.11) HU, which was lower than that in non-fracture group 7.74(-20.12, 44.54) HU (P<0.05). CT values on horizontal view in fracture group was 0.17(-23.13, 24.60) HU, which was lower than that in non-fracture group 46.40(10.42, 85.18) HU(P<0.05). The mean regional CT values among three planes in the fracture group were lower than those in the non-fracture group. Logistic regression analysis showed coronal CT value was influencing factors of proximal femoral fracture, and it could be written into regression equations that predict probability of fracture. CONCLUSION: In adults aged over 60 years old, CT values of cancellous bone of femoral neck decreased with increasing age. The smaller CT value of cancellous bone of femoral neck, the greater risk of proximal femoral fracture.

Are people living with HIV have a low vulnerability to omicron variant infection: results from a cross-sectional study in China.

BACKGROUND: A surge of more than 80 million Omicron variant infected cases was reported in China less than a month after the "zero COVID" strategy ended on December 7, 2022. In this circumstance, whether people living with HIV (PLWH) in China experience a similar risk is not clear. METHODS: A cross-sectional study was conducted in the Wuchang District of Wuhan between December 20, 2022, and January 18, 2023 through a self-administered online survey. PLWH and HIV-negative people aged ≥ 18 years old who volunteered for this survey were eligible. The prevalence of Omicron variant infection between PLWH and HIV-negative people was compared, and the factors associated with the Omicron variant infection among PLWH and HIV-negative people were further evaluated, respectively. RESULTS: In total, 890 PLWH and 1,364 HIV-negative adults from Wuchang District were enrolled. Among these participants, 690 PLWH (77.5%) and 1163 HIV-negative people (85.3%) reported SARS-CoV-2 infection. Gender, chronic disease conditions, and COVID-19 vaccination status significantly differed between the two groups. After adjusting gender, age, comorbidities, and COVID-19 vaccination status, the risk of SARS-CoV-2 infection among PLWH was significantly lower than among HIV-negative people (aOR 0.56, 95%CI 0.42-0.76). Multivariable logistic regression analysis showed that PLWH with older age and detectable HIV-viral load (HIV-VL) had decreased risk of SARS-CoV-2 infection (aOR 0.98, 95%CI 0.96-0.99; aOR 0.59, 95%CI 0.36-0.97). Compared with PLWH receiving one/two doses of COVID-19 vaccines, no significant differences in the risk of SARS-CoV-2 infection were observed among PLWH receiving three doses of inactivated vaccines and four doses of vaccines (three doses of inactivated vaccines plus one dose of inhaled recombinant adenovirus type 5 (AD5)-vectored vaccine). Among HIV-negative people, those receiving four doses of COVID-19 vaccines had a lower risk of SARS-CoV-2 infection than those receiving one/two doses (aOR 0.14, 95%CI 0.08-0.25). CONCLUSIONS: Our study proves that PLWH have a lower risk of Omicron variant infection than HIV-negative people. However, even PLWH with younger age and virological suppression should strengthen the prevention against SARS-CoV-2 infection. Three doses of inactivated vaccines plus one dose of inhaled recombinant AD5-vectored COVID-19 vaccine may provide better protection for HIV-negative people.

Case Report: Giant Oral Ulcers Attributed to Cytomegalovirus Infection in a Patient with AIDS.

Oral ulcers are often neglected in patients with AIDS. However, giant oral ulcers are uncommon and are usually suspected to be malignant lesions. Our study presents a case of giant ulcers in an AIDS patient that were initially suspected to be oral cancer. To assist with diagnosis, conventional microbiological tests, metagenomic next-generation sequencing, and a pathological examination were conducted on oral lesion biopsy specimens. The case was finally confirmed via hematoxylin-eosin staining and immunohistochemical staining to be a cytomegalovirus infection.

Microbiomes Detected by Bronchoalveolar Lavage Fluid Metagenomic Next-Generation Sequencing among HIV-Infected and Uninfected Patients with Pulmonary Infection.

Comparison of lung microbiomes between HIV-infected and uninfected patients with pulmonary infection by metagenomic next-generation sequencing (mNGS) has not been described in China. The lung microbiomes detected in bronchoalveolar fluid (BALF) by mNGS among HIV-infected and uninfected patients with pulmonary infection were reviewed in the First Hospital of Changsha between January 2019 and June 2022. In total, 476 HIV-infected and 280 uninfected patients with pulmonary infection were enrolled. Compared with HIV-uninfected patients, the proportions of Mycobacterium (P = 0.011), fungi (P < 0.001), and viruses (P < 0.001) were significantly higher in HIV-infected patients. The higher positive rate of Mycobacterium tuberculosis (MTB; P = 0.018), higher positive rates of Pneumocystis jirovecii and Talaromyces marneffei (all P < 0.001), and higher positive rate of cytomegalovirus (P < 0.001) contributed to the increased proportions of Mycobacterium, fungi, and viruses among HIV-infected patients, respectively. The constituent ratios of Streptococcus pneumoniae (P = 0.007) and Tropheryma whipplei (P = 0.002) in the bacteria spectrum were significantly higher, while the constituent ratio of Klebsiella pneumoniae (P = 0.005) was significantly lower in HIV-infected patients than in HIV-uninfected patients. Compared with HIV-uninfected patients, the constituent ratios of P. jirovecii and T. marneffei (all P < 0.001) in the fungal spectrum were significantly higher, while the constituent ratios of Candida and Aspergillus (all P < 0.001) were significantly lower in HIV-infected patients. In comparison to HIV-infected patients without antiretroviral therapy (ART), the proportions of T. whipplei (P = 0.001), MTB (P = 0.024), P. jirovecii (P < 0.001), T. marneffei (P < 0.001), and cytomegalovirus (P = 0.008) were significantly lower in HIV-infected patients on ART. Significant differences in lung microbiomes exist between HIV-infected and uninfected patients with pulmonary infection, and ART influences the lung microbiomes among HIV-infected patients with pulmonary infection. IMPORTANCE A better understanding of lung microorganisms is conducive to early diagnosis and treatment and will improve the prognosis of HIV-infected patients with pulmonary infection. Currently, few studies have systematically described the spectrum of pulmonary infection among HIV-infected patients. This study is the first to provide comprehensive information on the lung microbiomes of HIV-infected patients with pulmonary infection (as assessed by more sensitive metagenomic next-generation sequencing of bronchoalveolar fluid) compared with those from HIV-uninfected patients, which could provide a reference for the etiology of pulmonary infection among HIV-infected patients.

A tale of two conditions: when people living with HIV meet three doses of inactivated COVID-19 vaccines.

Background: Currently, data on long-term immune responses to a homogenous booster dose of the inactivated COVID-19 vaccine are still limited among people living with HIV (PLWH). Methods: A prospective cohort study with a 13-month follow-up was conducted in China between March 2021 and August 2022 to evaluate the dynamics of SARS-CoV-2 specific humoral and cellular immunity against three doses of the inactivated COVID-19 vaccine from before the first dose until 6 months after the booster dose vaccination among PLWH in comparison to healthy controls (HC). Results: 43 PLWH on antiretroviral therapy (ART) and 23 HC were enrolled. Compared with HC, the neutralizing antibodies (nAbs) levels among PLWH were significantly lower on days 14, 30, 60, 90, and 120 after the booster dose vaccination. Among PLWH, the nAbs titers on days 14, 30, and 60 after the booster dose were significantly higher than the peak of the second dose. However, on day 180 after the booster dose, the nAbs titers were similar to the peak of the second dose vaccination. Compared with HC, the frequencies of IFN-γ-secreting and TNF-α-secreting CD4+ and CD8+ T cells among PLWH were lower on days 14 and 180 after the booster dose vaccination. Among PLWH, increased T cell immunity was induced by the booster dose of the vaccine and kept stable on day 180 after the booster dose vaccination. Conclusion: Although a homogenous booster dose following two doses of the inactivated COVID-19 vaccine among PLWH could elicit higher nAb titers, reduce antibody decay, and maintain T cell responses even 6 months after vaccination, the overall immunogenicity of the booster dose was found to be lower among PLWH than among healthy controls. Further strategies are needed to improve immunogenicity to the inactivated COVID-19 vaccine among PLWH.

Characterization of peripheral cytokine-secreting cells responses in HIV/TB co-infection.

Background: Currently the responses of peripheral cytokine-secreting cells in the natural course of human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection haven't been fully elucidated. Methods: The function of peripheral proinflammatory, regulatory and cytotoxic cytokine-secreting cells were investigated by direct intracellular cytokine staining (ICS) and flow cytometry, additionally, the absolute numbers of different cytokine-secreting cells were measured among patients with HIV/TB co-infection (HT group), and compared them with the healthy controls (HC group), patients with TB (TB group) and patients with HIV infection (HIV group). After one week's anti-TB treatment, the changes of the percentages of cytokine-secreting cells were further evaluated in TB and HT groups. Results: Totally 26 individuals in the HC group, 51 in the TB group, 26 in the HIV group and 29 in the HT group were enrolled. The HT. HT group exhibited significantly lower absolute numbers of IFN-γ+CD4+, IFN-γ+CD8+, TNF-α+CD4+, IL17A+CD4+ T cells and TNF-α+CD14+ monocytes than the TB and HIV groups. Compared with the TB group, the percentages of CD8+ T cells secreting IFN-γ and perforin (p=0.010; p=0.043) were significantly lower among the HT group. Compared with the HIV group, the percentages of CD4+, CD8+ T cells and CD14+ monocytes secreting TNF-α (p=0.013; p=0.001; p<0.001) were significantly decreased, and the percentage of CD8+ T cells secreting IL-17A (p=0.015) was significantly increased among the HT group. Both the percentages of CD4+ T cells secreting TGF-ß (p<0.001; p=0.001), and CD4+ and CD8+ T cells secreting granzyme A (all p<0.001), were significantly higher among the HT group than among the TB group and HIV group. After one week's anti-TB treatment, an increased percentage of CD4+ T cells secreting TNF-α (p=0.003) was found in the TB group, and an increased percentage of CD8+ T cells secreting TNF-α (p=0.029) was found in the HT group. Conclusion: Significantly different functional profiles of peripheral proinflammatory, regulatory, and cytotoxic cytokine-secreting cells were observed in the natural course of HIV/TB co-infection compared to TB and HIV infection alone, even though the absolute numbers of those cells were significantly lower in HIV/TB co-infection. TNF-α-secreting CD8+ T cells may be a more sensitive marker for early evaluation of anti-TB treatment efficacy in patients with HIV/TB co-infection.

Adverse pregnancy outcomes associated with antiretroviral therapy initiated before pregnancy and during pregnancy: a retrospective study in Hubei province, China.

Background: Antiretroviral therapy (ART) initiation before pregnancy was reported to have an increased risk of adverse pregnancy outcomes (APOs) than ART initiation during pregnancy. However, the risks of APOs associated with different ART regimens initiated before or during pregnancy remain unknown. Methods: Pregnant women living with HIV (PWLHIV) from Hubei Province, China, were retrospectively enrolled between January 1, 2004, and December 31, 2021. The trends of ART initiation time and application of different ART regimens were evaluated over time, separately. Using no ART exposure before and during pregnancy as control, the risks of APOs associated with protease inhibitor (PI) based regimens and non-nucleoside reverse transcriptase inhibitors (NNRTIs) based regimens initiated before pregnancy were analyzed; and the risks of APOs associated with PI-based regimens, NNRTIs based regimens and zidovudine (AZT) monotherapy initiated during pregnancy were analyzed. APOs, including low birthweight (LBW), stillbirth, preterm birth (PTB) and early miscarriage, were reviewed. Results: Among 781 PWLHIV including 1,010 pregnancies, 522 pregnancies (51.7%) were exposed to ART before or during pregnancy. Of them, the proportion of ART initiation before pregnancy per year increased from around 20% in the early period to more than 60% after 2019. Efavirenz (EFV)-nucleoside reverse transcriptase inhibitors (NRTIs) (32.2%), LPV/r-NRTIs (31.2%), and nevirapine (NVP)-NRTIs (27.4%) were the most commonly used regimens, and the proportion of LPV/r-NRTIs used per year has increased to around 50.0% in recent years. LPV/r-NRTIs was associated with higher risks of LBW whether initiated before pregnancy [adjusted OR (aOR) = 2.59, 95%CI 1.04-6.45, p = 0.041] or during pregnancy (aOR = 2.19, 95%CI 1.03-4.67, p = 0.041), compared with no exposure to ART before and during pregnancy. However, no matter initiated before or during pregnancy, LPV/r-NRTIs had no significantly increased risks of stillbirth, PTB and early miscarriage, and EFV /NVP-NRTIs and AZT monotherapy had no significantly increased risks of LBW, stillbirth, PTB and early miscarriage when compared with no exposure to ART before and during pregnancy. Conclusion: Our data suggests that LPV/r-NRTIs has been widely used among PWLHIV in recent years. However, the potential risk of LBW should be continuously monitored among PWLHIV whether LPV/r-NRTIs is initiated before or during pregnancy.

Metagenomic next-generation sequencing versus traditional laboratory methods for the diagnosis of central nervous system opportunistic infections in HIV-infected Chinese adults.

To evaluate clinical value of metagenomic next-generation sequencing (mNGS) in people living with HIV/AIDS (PLWHA) who had CNS disorders. Cerebrospinal fluid (CSF) samples from 48 PLWHA presenting with CNS disorders were sequenced using mNGS and compared with clinical conventional diagnostic methods. In total, 36/48 ss(75%) patients were diagnosed with pathogen(s) infection by mNGS, and the positive detection proportion by mNGS was higher than that by clinical conventional diagnostic methods (75% vs 52.1%, X2 = 5.441, P = 0.020). Thirteen out of 48 patients (27.1%) were detected with 3-7 pathogens by mNGS. Moreover, 77 pathogen strains were detected, of which 94.8% (73/77) by mNGS and 37.0% (30/77) by clinical conventional methods (X2 = 54.206, P < 0.001). The sensitivity and specificity of pathogens detection by mNGS were 63.9% (23/36) and 66.7% (8/12), respectively, which were superior to that by clinical conventional methods (23/36 vs 9/25, X2 = 4.601, P = 0.032; 8/12 vs 5/23, X2 = 5.029, P = 0.009). The application of mNGS was superior for its ability to detect a variety of unknown pathogens and multiple pathogens infection, and relatively higher sensitivity and specificity in diagnosis of CNS disorders in PLWHA.