Association between long-term exposure to fine particulate matter and its chemical constituents and premature death in individuals living with HIV/AIDS.

Long-term exposure to fine particulate matter (PM2.5) is associated with an increased total mortality. However, the association of PM2.5 with mortality in people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS, PLWHA) and the relationship between its constituents and adverse outcomes remain unknown. In this cohort study, 28,140 PLWHA were recruited from the HIV/AIDS Comprehensive Response Information Management System of the Hubei Provincial Centre for Disease Control and Prevention in China between 2001 and 2020. The annual PM2.5 chemical composition data, including sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), black carbon (BC), and organic matter (OM), was extracted from the Tracking Air Pollution (TAP) dataset in China. A Cox proportional hazard model with time-varying exposure and time-to-event quantile-based generalized (g) computation was used to assess the associations between PM2.5 chemical constituents, and mortality in PLWHA. A multivariate Cox proportional hazard model estimated an excess hazard ratio (eHR) of 0.32% [95% confidence interval (CI): (0.01%, 0.64%)] for AIDS-related death (ARD), associated with 1 µg/m3 rise in PM2.5 exposure. An increase of 1 µg/m3 in NH4+ was associated with 5.13% [95% CI: (2.89%, 7.43%)] and 2.97% [95% CI: (1.52%, 4.44%)] increase in the risk of ARD and all-cause deaths (ACD), respectively. When estimated using survival-based quantile g-computation, the eHR for ARD with a joint change in a decile increase in all five components was 6.10% [95% CI: 3.77%, 8.48%)]. Long-term exposure to PM2.5 chemical composition, particularly NH4+ increased the risk of death in PLWHA. This study provides epidemiological evidence that SO42- and NH4+ increased the risk of ARD and that NH4+ increased the risk of ACD in PLWHA. Multi-constituent analyses further suggested that NH4+ may be a key component in increasing the risk of premature death in patients with HIV/AIDS. Individuals aged ≥65 with HIV/AIDS are more vulnerable to SO42-, and consequent ACD.

Is short-term exposure to primary gaseous air pollutants associated with AIDS-related deaths? Evidence from a time-stratified case-crossover study.

Primary gaseous air pollutants have been associated with death from multiple causes, however, it remains unknown if they play a role in premature mortality among individuals living with HIV/AIDS. Data on HIV/AIDS patients were collected from the Hubei Provincial Center for Disease Control and Prevention, with a total of 1,467 AIDS-related deaths (ARD) between 2013 and 2020. Daily mean sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) were generated by artificial intelligence algorithms combined with big data. We employed a time-stratified case-crossover approach and conditional logistical regression models to investigate the acute effects of primary gaseous air pollutants on ARD. Per interquartile range increase in the concentrations of SO2 was significantly linked with ARD, with a corresponding odds ratio (OR) of 1.17 [95% confidence intervals (CIs): 1.01, 1.35] at lag 4 day. Furthermore, our findings indicated that males exhibited a heightened vulnerability to the adverse effects of SO2 and NO2, for example, the ORs were 1.24 (95% CIs: 1.05, 1.47) and 1.16 (95% CIs: 1.01, 1.34), respectively. Moreover, individuals aged over 65 years were more susceptible to SO2 and CO. Additionally, we identified the warm season as a sensitive period for mortality associated with SO2 and NO2. Our study furnished fresh evidence regarding the detrimental effects of primary gaseous air pollutants on ARD.

Ambient temperature variations and AIDS-related mortality: A time-stratified case-crossover study in 103 counties, China.

BACKGROUND: Climate change, characterized by the steady ascent of global temperatures and the escalating unpredictability of climate patterns, poses multifaceted challenges to public health worldwide. However, vulnerable groups, particularly the population affected by HIV/AIDS, have received little attention. OBJECTIVES: We aimed to examine the impacts of temperature variations on AIDS-related mortality. METHODS: Data on individuals with HIV/AIDS were collected from the HIV/AIDS Comprehensive Response Information Management System between 2013 and 2019. Temperature variation metrics were constructed by diurnal temperature range (DTR), temperature changes between neighboring days (TCN), and temperature variability (TV0-t). Time-stratified case-crossover design with conditional logistic regression models was used to investigate the associations between ambient temperature variations and AIDS-related mortality. RESULTS: Each 1 °C elevated in DTR was linked with a 5.28 % [95 % confidence intervals (CIs): 1.61, 9.08] increment in AIDS-related mortality at a lag of 0-6 days. Stronger associations between DTR and AIDS-related mortality were observed in the married than in single, with corresponding excess ORs (%) of 5.33 (95 % CIs: 0.29, 10.62) versus 4.79 (95 % CIs: -0.50, 10.36) for 1 °C increased in DTR at lag 0-6 days. Additionally, we noticed the impact of DTR was more pronounced in the warm season, leading to a 7.32 % (95 % CIs: 0.57, 14.51) elevation in the risks of AIDS-related mortality for 1 °C increase in DTR at lag 0-6 days, while the effect value decreased to 5.16 % (95 % CIs: 0.71, 9.81) in the cold season. CONCLUSIONS: Our findings indicated that DTR might be a significant risk factor for AIDS-related deaths among ambient temperature variation indicators, and underscored the importance of considering temperature variability in public health interventions aimed at mitigating this risk of AIDS-related mortality.

Submicronic particulate matter (PM1), a "neglected killer" for HIV/AIDS patients in Hubei, China: Results from a cohort study from 2001 to 2020.

BACKGROUND: Although with the progress of antiretroviral therapy, the life expectancy of HIV/AIDS patients was still not equal to that of normal people. Submicronic particulate matter (PM1) might play a role in mortality among people living with HIV/AIDS, However, cohort evidence is extensively scarce. METHODS: This twenty-year open cohort study involved all individuals officially diagnosed with HIV/AIDS in Hubei Province from 2001 to 2020. Time-varying Cox proportional hazard models were applied to investigate the associations between long-term exposure to PM1 and mortality in HIV/AIDS patients. The concentration-response curves between PM1 and AIDS-related deaths/all-cause deaths were characterized by fitting restricted cubic spline models. These curves were then utilized to estimate the number of deaths attributed to PM1. RESULTS: Long-term exposure to PM1 was significantly associated with AIDS-related deaths and all-cause death among HIV/AIDS patients, with excess risks of 2.33 % [95 % confidence interval (CIs): 1.62, 3.15] and 0.69 % (0.22, 1.17) for each 1 µg/m3 increase in annual PM1. HIV-positive people with lower initial CD4+ cell count levels or aged over 65 years old were more susceptible to PM1 exposure. We estimated about 844 AIDS-related deaths and 1175 all-cause deaths can be attributable to ambient PM1 exposure, accounting for 41.7 % and 23.8 % of the total deaths from corresponding causes, respectively. CONCLUSIONS: Long-term exposure PM1 was a novel factor hindering the life spans of people living with HIV/AIDS. Early establishment of PM1 concentration standards and efforts to achieve them will bring substantial health benefits to people living with HIV/AIDS, especially in low- and middle-income countries facing the dual challenges of high air pollution and high AIDS prevalence.

Incomplete immune reconstitution and its predictors in people living with HIV in Wuhan, China.

OBJECTIVE: This study aimed to build and validate a nomogram model to predict the risk of incomplete immune reconstitution in people living with HIV (PLWH). METHODS: Totally 3783 individuals with a confirmed diagnosis of HIV/AIDS were included. A predictive model was developed based on a retrospective set (N = 2678) and was validated using the remaining cases (N = 1105). Univariate and multivariate logistic regression analyses were performed to determine valuable predictors among the collected clinical and laboratory variables. The predictive model is presented in the form of a nomogram, which is internally and externally validated with two independent datasets. The discrimination of nomograms was assessed by calculating the area under the curve (AUC). Besides, calibration curve and decision curve (DCA) analyses were performed in the training and validation sets. RESULTS: The final model comprised 5 predictors, including baseline CD4, age at ART initiation, BMI, HZ and TBIL. The AUC of the nomogram model was 0.902, 0.926, 0.851 in the training cohort, internal validation and external cohorts. The calibration accuracy and diagnostic performance were satisfactory in both the training and validation sets. CONCLUSIONS: This predictive model based on a retrospective study was externally validated using 5 readily available clinical indicators. It showed high performance in predicting the risk of incomplete immune reconstitution in people living with HIV.

Recent advances in poor HIV immune reconstitution: what will the future look like?

Combination antiretroviral therapy has demonstrated proved effectiveness in suppressing viral replication and significantly recovering CD4+ T cell count in HIV type-1 (HIV-1)-infected patients, contributing to a dramatic reduction in AIDS morbidity and mortality. However, the factors affecting immune reconstitution are extremely complex. Demographic factors, co-infection, baseline CD4 cell level, abnormal immune activation, and cytokine dysregulation may all affect immune reconstitution. According to report, 10-40% of HIV-1-infected patients fail to restore the normalization of CD4+ T cell count and function. They are referred to as immunological non-responders (INRs) who fail to achieve complete immune reconstitution and have a higher mortality rate and higher risk of developing other non-AIDS diseases compared with those who achieve complete immune reconstitution. Heretofore, the mechanisms underlying incomplete immune reconstitution in HIV remain elusive, and INRs are not effectively treated or mitigated. This review discusses the recent progress of mechanisms and factors responsible for incomplete immune reconstitution in AIDS and summarizes the corresponding therapeutic strategies according to different mechanisms to improve the individual therapy.

Short-term exposure to ozone and mortality from AIDS-related diseases: A case-crossover study in the middle Yangtze River region, China.

BACKGROUND: Previous investigations have predominantly concentrated on the influence of ozone (O3) on general population mortality. However, a noticeable gap exists regarding the attention directed towards susceptible demographics, specifically individuals afflicted by human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). METHODS: A dataset comprising 1467 AIDS-related fatalities from 2013 to 2020 was amassed from the Hubei Provincial Center for Disease Control and Prevention. Daily maximum 8-h average O3 levels and meteorological parameters were extracted from the ChinaHighAirPollutants dataset and the National Meteorological Science Data Center, respectively. A time-stratified case-crossover methodology was employed to scrutinize the connection between short-term exposure to O3 and AIDS-related deaths. RESULTS: A rise of one interquartile (IQR) in O3 concentration, lagged by 4 days, was associated with a 15% [95% confidence intervals (CIs): 2, 31] increase in AIDS-related deaths. Notably, males demonstrated heightened susceptibility to the adverse consequences of O3, marked by an odds ratio of 1.20 (95% CIs: 1.05, 1.37) at lag 4 day. Additionally, patients aged over 65 years exhibited escalated vulnerability to brief O3 exposure. Marriage status and educational attainment emerged as influential factors modifying the interplay between O3 and AIDS-related mortality. CONCLUSIONS: Our study presents novel evidence spotlighting the deleterious repercussions of O3 on mortality in the HIV/AIDS population.

Development and validation of a scoring system for the prediction of HIV drug resistance in Hubei province, China.

Objective: The present study aimed to build and validate a new nomogram-based scoring system for the prediction of HIV drug resistance (HIVDR). Design and methods: Totally 618 patients with HIV/AIDS were included. The predictive model was created using a retrospective set (N = 427) and internally validated with the remaining cases (N = 191). Multivariable logistic regression analysis was carried out to fit a model using candidate variables selected by Least absolute shrinkage and selection operator (LASSO) regression. The predictive model was first presented as a nomogram, then transformed into a simple and convenient scoring system and tested in the internal validation set. Results: The developed scoring system consisted of age (2 points), duration of ART (5 points), treatment adherence (4 points), CD4 T cells (1 point) and HIV viral load (1 point). With a cutoff value of 7.5 points, the AUC, sensitivity, specificity, PLR and NLR values were 0.812, 82.13%, 64.55%, 2.32 and 0.28, respectively, in the training set. The novel scoring system exhibited a favorable diagnostic performance in both the training and validation sets. Conclusion: The novel scoring system can be used for individualized prediction of HIVDR patients. It has satisfactory accuracy and good calibration, which is beneficial for clinical practice.

Ambient particulate matter, a novel factor hindering life spans of HIV/AIDS patients: Evidence from a ten-year cohort study in Hubei, China.

BACKGROUND: The life spans of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients have been extended in the era of antiretroviral therapy. However, few studies have considered the influence of the environment on the life expectancy of people living with HIV/AIDS. Several studies have investigated mortality and air pollution associations, but the evidence for associations between long-term exposure to particulate matter (PM) and mortality among HIV/AIDS patients remains extremely sparse. METHODS: We conceived a dynamic cohort study by enrolling people with HIV/AIDS from 103 counties in Hubei province, China from 2010 to 2019, with 23,809 persons and 78,457.2 person-years of follow-up. The county-level annual concentrations of PM2.5 and PM10 were extracted from the ChinaHighAirPollutants dataset. Cox proportional hazards models with time-varying exposures were conducted to assess the associations between PM and mortality. RESULTS: Per 1 µg/m3 increased in PM2.5 and PM10 would elevate 0.69 % (95 % CIs: 0.39, 1.00) and 0.39 % (95 % CIs: 0.18, 0.59) risk of all-cause deaths (ACD) and 1.65 % (95 % CIs: 1.14, 2.17) and 0.90 % (95 % CIs: 0.56, 1.24) of AIDS-related deaths (ARD), respectively. Significantly stronger associations of PM-ARD were found in patients aged over 60 years old, with corresponding excess risk of 2.66 % (95 % CIs: 1.76, 3.58) for PM2.5 and 1.62 (95 % CIs: 1.01, 2.23) for PM10. CONCLUSIONS: This study added to the existing evidence that long-term exposure to ambient PM adversely affects the life spans of HIV/AIDS patients. Hence, public health departments should take proactive measures to prevent further life loss and promote survival among those living with HIV/AIDS.

Analysis of the Influencing Factors of Immunological Nonresponders in Wuhan, China.

Objective: CD4+ cell recovery is hampered in some human immunodeficiency virus (HIV)-infected patients, despite a successful highly active antiretroviral therapy (HAART) with suppressed viral replication. We investigated the factors that might have hindered the CD4+ cell recovery in these patients. Methods: In this retrospective study, we collected the data of all immune nonresponders (INRs) in Wuhan, China, until the end of 2020. A linear model was constructed based on the data from 220 patients with baseline and follow-up records. The response variables in this study were the CD4+ cell count increase. The predictor variables considered in this study were those factors likely to affect the CD4+ cell recovery. Results: Our findings revealed that the plasma HIV-1 viral load of all patients was suppressed and 87.3% patients' CD4+ cells was increased after more than one year of the HAART treatment. In addition, their last follow-up showed a significant reduction in complications. In our results, the body mass index (BMI), number of months since HIV diagnosis to HAART start, and nonuse of co-trimoxazole were negatively correlated with the increase in CD4+ cells (P < 0.05). However, there were positive associations between serum creatinine levels and CD4+ cell recovery (P < 0.05). Further stratified analyses indicated that the associations between HAART replacement or creatinine usage and CD4+ cell growth were only observed in those participants with a BMI <18.5 (P < 0.05). Conclusions: An early initiation of HAART and co-trimoxazole preventive therapy (CPT) can promote immune reconstitution. BMI and serum creatinine can serve as monitoring indicators of immune reconstitution prognosis after the HAART.

Correction: Li et al. Altered Salivary Microbiome in the Early Stage of HIV Infections among Young Chinese Men Who Have Sex with Men (MSM). Pathogens 2020, 9, 960.

In the original publication [...].

Comparing different machine learning techniques for predicting COVID-19 severity.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is still ongoing spreading globally, machine learning techniques were used in disease diagnosis and to predict treatment outcomes, which showed favorable performance. The present study aims to predict COVID-19 severity at admission by different machine learning techniques including random forest (RF), support vector machine (SVM), and logistic regression (LR). Feature importance to COVID-19 severity were further identified. METHODS: A retrospective design was adopted in the JinYinTan Hospital from January 26 to March 28, 2020, eighty-six demographic, clinical, and laboratory features were selected with LassoCV method, Spearman's rank correlation, experts' opinions, and literature evaluation. RF, SVM, and LR were performed to predict severe COVID-19, the performance of the models was compared by the area under curve (AUC). Additionally, feature importance to COVID-19 severity were analyzed by the best performance model. RESULTS: A total of 287 patients were enrolled with 36.6% severe cases and 63.4% non-severe cases. The median age was 60.0 years (interquartile range: 49.0-68.0 years). Three models were established using 23 features including 1 clinical, 1 chest computed tomography (CT) and 21 laboratory features. Among three models, RF yielded better overall performance with the highest AUC of 0.970 than SVM of 0.948 and LR of 0.928, RF also achieved a favorable sensitivity of 96.7%, specificity of 69.5%, and accuracy of 84.5%. SVM had sensitivity of 93.9%, specificity of 79.0%, and accuracy of 88.5%. LR also achieved a favorable sensitivity of 92.3%, specificity of 72.3%, and accuracy of 85.2%. Additionally, chest-CT had highest importance to illness severity, and the following features were neutrophil to lymphocyte ratio, lactate dehydrogenase, and D-dimer, respectively. CONCLUSIONS: Our results indicated that RF could be a useful predictive tool to identify patients with severe COVID-19, which may facilitate effective care and further optimize resources.

Effects of Case Management on Risky Sexual Behaviors and Syphilis Among HIV-Infected Men Who Have Sex With Men in China: A Randomized Controlled Study.

BACKGROUND: The prevalence of syphilis is very high in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM), and effective interventions are needed to educate HIV-positive individuals about behavioral and biological risk factors. Therefore, we developed a standard case management process and conducted a randomized controlled study to investigate the impact on risky sexual behaviors and syphilis in HIV-positive MSM. METHODS: Men who have sex with men (n = 220) were enrolled and randomized to the case management intervention group and the control group between May 2016 and January 2017. The control group received routine HIV-related care. In addition to routine HIV-related care, those in the intervention group regularly received extended services from a well-trained case manager. Epidemiological information was collected during the baseline face-to-face interviews by a trained investigator. Serological tests for syphilis and assessments of risky sexual behaviors were performed at baseline and 6 and 12 months after the initiation of treatment. RESULTS: The syphilis incidence rates in the intervention and control groups were 11.3 per 100 person-years and 20.6 per 100 person-years, respectively. The multivariable-adjusted hazard ratio (95% confidence inter) for syphilis in case management group was 0.34 (0.14-0.87). The percentages of participants who resumed risky sexual behaviors in both groups were significantly reduced (P < 0.05) but did not significantly differ between the 2 groups. CONCLUSIONS: A case management intervention reduced the incidence of syphilis in HIV-positive MSM. We should further increase the content of case management on the basis of providing routine HIV-related care to those people.

The effect of Huashibaidu formula on the blood oxygen saturation status of severe COVID-19: A retrospective cohort study.

BACKGROUND: Huashibaidu Formula (HSBD) for the COVID-19 treatment has been supported by the China's Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia. However, it is not clear whether HSBD can improve blood oxygen saturation and when it should be used with conventional therapies. PURPOSE: To access the effect of HSBD combined with conventional treatment on blood oxygen saturation of COVID-19 patients. METHODS: A single-center retrospective cohort study was conducted to collect the confirmed severe COVID-19 patients' information, treated by the National Traditional Chinese Medicine Medical Team at the Jinyintan hospital between January 24 and March 31, 2020. According to whether HSBD was used during hospitalization, participants were separated into the conventional treatment group and the HSBD group (HSBD and conventional treatment). The primary observation indicators included the time for relieving blood oxygen saturation and the improvement ratio of blood oxygen saturation in each group. RESULTS: Of 111 patients with severe COVID-19, 53.2% (59/111) received HSBD, and 46.8% (52/111) only received conventional treatment, respectively. No statistically significant difference was found in image, clinical symptoms, and past medical history between the two groups (p > 0.05). Notably, the median time for relieving blood oxygen saturation in the conventional treatment group was 11 days (IQR, 8-14.25), while that in the HSBD group was only 6 days (IQR, 3.25-10.75), which was significantly shortened by 4.09 days (95%CI, 2.07-6.13; p= 0.0001), compared with the conventional treatment group. After repeated measurement design analysis, the main effect within times (p< 0.001) and the main effect were significantly different under the oxygen saturation dimension between two groups (p= 0.004). However, time and group interaction were observed no significant difference (p= 0.094). After 14 days of treatment, the improvement ratio of the HSBD group over the conventional treatment group was 1.20 (95%CI, 0.89-1.61). CONCLUSION: For severe COVID-19 patients, the HSBD has a tendency to shorten the time for relieving blood oxygen saturation. After taking a course of HSBD, the effect can be more obvious.

Comparative Analysis of Salivary Mycobiome Diversity in Human Immunodeficiency Virus-Infected Patients.

Reports on alterations in the oral mycobiome of HIV-infected patients are still limited. This study was designed to compare the salivary mycobiome between 30 human immunodeficiency virus (HIV) infections and 30 healthy controls and explore the effect of antiretroviral therapy (ART) administration on the oral mycobiome of HIV infections. Results showed that the diversity and richness of salivary mycobiome in HIV-infected individuals were higher than those of controls (P < 0.05). After ART, the diversity and richness of salivary mycobiome in HIV-infected patients were reduced significantly (P < 0.05). Candida, Mortierella, Malassezia, Simplicillium, and Penicillium were significantly enriched in the HIV group and dramatically decreased after ART. While the relative abundance of Verticillium, Issatchenkia, and Alternaria significantly increased in patients with HIV after ART. Correlation analysis revealed that Mortierella, Malassezia, Simplicillium, and Chaetomium were positively correlated with viral load (VL), whereas Thyrostroma and Archaeorhizomyces were negatively related to VL and positively related to CD4+ T-cell counts. All results showed that HIV infection and ART administration affected the composition of salivary mycobiome communities. Furthermore, differences of salivary mycobiome in HIV infections after ART were complex and might mirror the immune state of the body.

Combination of Hua Shi Bai Du granule (Q-14) and standard care in the treatment of patients with coronavirus disease 2019 (COVID-19): A single-center, open-label, randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of Hua Shi Bai Du Granule (Q-14) plus standard care compared with standard care alone in adults with coronavirus disease (COVID-19). STUDY DESIGN: A single-center, open-label, randomized controlled trial. SETTING: Wuhan Jinyintan Hospital, Wuhan, China, February 27 to March 27, 2020. PARTICIPANTS: A total of 204 patients with laboratory-confirmed COVID-19 were randomized into the treatment group and control group, consisting of 102 patients in each group. INTERVENTIONS: In the treatment group, Q-14 was administered at 10 g (granules) twice daily for 14 days, plus standard care. In the control group, patients were provided standard care alone for 14 days. MAIN OUTCOME MEASURE: The primary outcome was the conversion time for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral assay. Adverse events were analyzed in the safety population. RESULTS: Among the 204 patients, 195 were analyzed according to the intention-to-treat principle. A total of 149 patients (71 vs. 78 in the treatment and control groups, respectively) tested negative via the SARS-CoV-2 viral assay. There was no statistical significance in the conversion time between the treatment group and control group (Full analysis set: Median [interquartile range]: 10.00 [9.00-11.00] vs. 10.00 [9.00-11.00]; Mean rank: 67.92 vs. 81.44; P = 0.051). The recovery time for fever was shorter in the treatment group than in the control group. The disappearance rate of symptoms like cough, fatigue, and chest discomfort was significantly higher in the treatment group. In chest computed tomography (CT) examinations, the overall evaluation of chest CT examination after treatment compared with baseline showed that more patients improved in the treatment group. There were no significant differences in the other outcomes. CONCLUSION: The combination of Q-14 and standard care for COVID-19 was useful for the improvement of symptoms (such as fever, cough, fatigue, and chest discomfort), but did not result in a significantly higher probability of negative conversion in the SARS-CoV-2 viral assay. No serious adverse events were observed. TRIAL REGISTRATION: ChiCTR2000030288.