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This study aims to develop and evaluate a model to predict the immune reconstitution among HIV/AIDS patients after antiretroviral therapy (ART). A total of 502 HIV/AIDS patients are randomized to the training cohort and evaluation cohort. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis are performed to identify the indicators and establish the nomogram for predicting the immune reconstitution. Decision curve analysis (DCA) and clinical impact curve (CIC) are used to evaluate the clinical effectiveness of the nomogram. Predictive factors included white blood cells (WBC), baseline CD4+ T‐cell counts (baseline CD4), ratio of effector regulatory T cells to resting regulatory T cells (eTreg/rTreg) and low‐density lipoprotein cholesterol (LDL‐C) and are incorporated into the nomogram. The area under the curve (AUC) is 0.812 (95% CI, 0.767∼0.851) and 0.794 (95%CI, 0.719∼0.857) in the training cohort and evaluation cohort, respectively. The calibration curve shows a high consistency between the predicted and actual observations. Moreover, DCA and CIC indicate that the nomogram has a superior net benefit in predicting poor immune reconstitution. A simple‐to‐use nomogram containing four routinely collected variables is developed and internally evaluated and can be used to predict the poor immune reconstitution in HIV/AIDS patients after ART. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated the impact of low‐level viremia (LLV) on virological failure and immune reconstitution among people living with human immunodeficiency virus type 1 (HIV‐1) treated with different antiretroviral regimens in Beijing, China. Methods: Human immunodeficiency virus type 1‐positive adults who were registered at an infectious disease hospital in Beijing between January 1, 2005 and January 1, 2020 were administered antiretroviral therapy (ART) and whose viral load and CD4 counts were monitored were included in this retrospective cohort study. Univariate and multivariate logistic regression analyses were performed to identify risk factors associated with LLV in patients on different ART regimens. Cox proportional hazard model was employed to analyze the virological suppression and immune reconstitution cumulative probability in patients with LLV during follow‐up. Results: A total of 10 124 HIV‐1‐infected participants was included. LLV occurred in 723 (8.2%), 204 (10.9%), 133 (8.6%), and 53 (14.4%) patients on first‐line ART, second‐line ART, third‐line ART, and simplified regimens, respectively. Virological failure occurred in 514 (5.8%), 289 (15.5%), 86 (5.5%), and 34 (9.2%) patients on first‐line ART, second‐line ART, third‐line ART, and simplified regimens, respectively. Earlier enrollment, lower baseline CD4 count, and higher baseline viral load were risk factors associated with LLV. LLV was related to increased hazards of virological failure compared to viral suppression of ≤50 copies/ml for those on first‐line ART. Conclusions: The risk of virological failure and poor immune reconstitution increases when LLV occurs. Targeted viral load and CD4 count monitoring are recommended for people living with HIV‐1 with LLV to improve health‐related outcomes. [ABSTRACT FROM AUTHOR]

Objective: To analyze immune reconstitution and influencing factors in HIV infected men who have sex with men (MSM) with access to antiviral therapy (ART) in Guangxi Zhuang Autonomous Region (Guangxi) during 2005-2021. Methods: The data were collected from Chinese Disease Prevention and Control Information System. The study subjects were HIV infected MSM with access to the initial ART for ≥24 weeks in Guangxi from 2005 to 2021 and HIV RNA lower than the detection limit within 24 months. The proportion of infected MSM who had immune reconstitution after ART was calculated. Cox proportional hazard regression model was used to analyze the influencing factors of immune reconstitution. Software SPSS 24.0 was used for statistical analysis. Results: A total of 3 200 HIV infected MSM were enrolled, in whom 15.56 % (498/3 200) had no immune reconstitution, 14.78% (473/3 200) had moderate immune reconstitution, and the rate of complete immune reconstitution was 69.66% (2 229/3 200). The M ( Q 1 ) of ART time for immune reconstitution was 12 (5, 27) months. Multivariate Cox proportional risk regression model analysis results showed that compared with those with initial ART at age ≥30 years, WHO clinical stage Ⅲ/Ⅳ illness, baseline BMI <18.50 kg/m Q 3 ) of ART time for immune reconstitution was 12 (5, 27) months. Multivariate Cox proportional risk regression model analysis results showed that compared with those with initial ART at age ≥30 years, WHO clinical stage Ⅲ/Ⅳ illness, baseline BMI <18.50 kg/m 2 and baseline CD4 counts ≥200 cells/µl were more likely to have complete immune reconstitution. + In the HIV infected MSM in Guangxi, failures to achieve moderate and complete immune reconstitution were observed. Surveillance and ART regimen should be improved for key populations, such as those with older age and low baseline CD4 counts.2 and baseline CD4 counts ≥200 cells/µl were more likely to have complete immune reconstitution. Conclusions: In the HIV infected MSM in Guangxi, failures to achieve moderate and complete immune reconstitution were observed. Surveillance and ART regimen should be improved for key populations, such as those with older age and low baseline CD4 counts.

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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: To describe the clinical characteristics and factors associated with CD4 T-cell count and CD4/CD8 ratio restoration in HIV mono-infected and HIV/HBV co-infected individuals, and to explore liver and renal functional changes in both groups., Methods: A retrospective cohort study was performed including 356 HIV/HBV co-infected and 716 HIV mono-infected participants who initiated antiretroviral therapy (ART) during 2013-2017 in Beijing Youan Hospital, China. Demographic and clinical characteristics were compared between the two groups, using χ 2 and Mann-Whitney non-parametric tests. Bivariate and multivariate Cox regression models were used to test their association., Results: Baseline HIV viral load and ART regimen were found to be significantly associated with CD4 T-cell restoration among HIV-infected participants, whereas baseline HIV viral load was the only significant factor associated with CD4 T-cell restoration in HIV/HBV co-infected participants. The final model showed that baseline HIV viral load and ART regimen were significantly associated with CD4/CD8 ratio restoration among HIV-infected participants, while baseline HIV viral load was the significant factor. Liver and renal functions were similar at the endpoint (P > 0.05)., Conclusions: Baseline HIV viral load count was found to be the key factor affecting immune restoration in both HIV and HIV/HBV individuals. Future multi-wave prospective studies are needed to clarify the potential biological mechanism., (© 2020 British HIV Association.)

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. [ABSTRACT FROM AUTHOR]

Background: Body mass index (BMI) may contribute somewhat to drug metabolism, and thus affecting the efficacy of highly active antiretroviral therapy (HAART). This study aimed to determine the frequencies of underweight, normal and overweight/obesity at pre-HAART in a large cohort of HIV-infected Chinese patients, and investigate the prospective effects of BMI on immune reconstitution after HAART initiation.Methods: A longitudinal cohort study was performed to analyze the effects of BMI on immune reconstitution in HIV-infected patients treated with HAART. Multiple linear regression was used to evaluate the relationship between baseline BMI and increased CD4+ T lymphocyte levels at 12 and 30 months after initiating HAART. In addition, Cox proportional hazard model was used to assess the relationship between BMI and time to achieve immunologic reconstitution (CD4+ T lymphocytes>500cells/μL) during the follow-up period.Results: Among the 1612 enrolled patients, 283 (17.6%) were overweight/obese (BMI ≥ 25 kg/m2), 173 (10.7%) were underweight (BMI < 18.5 kg/m2) and the remaining were normal weight. Prior to HAART initiating, overweight HIV-infected patients were mostly males, older ages, exhibited higher CD4+ T lymphocytes and lower viral loads (p < 0.01 for all). Patients with higher baseline BMI had an independently positive effect on 30-month CD4+ T lymphocyte recovery (p = 0.028), but not 12-month CD4+ T lymphocyte gain (p = 0.104). In addition, a Cox proportional hazard model with baseline BMI as an independent variable indicated that BMI was correlated with an increased likelihood of achieving immunologic reconstitution over time (hazard ratios [HR] 1.03; 95% confidence intervals [CI] 1.01-1.06; p = 0.011), after adjusting for baseline age, gender, CD4+ T lymphocytes, CD4/CD8 ratio, viral load and WHO stage.Conclusions: Higher baseline BMI could predict better immune reconstitution in HIV-infected patients after HAART initiating. [ABSTRACT FROM AUTHOR]

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 profound deficiency of Th17 cells contributes to HIV disease progression. The mechanisms of their perturbation remain unclear. Recently, CCR6 + CD95 + CD4 + naïve T cells (CCR6 + CD95 + CD4 + T NA ), identified as pre-committed Th17 precursors, were recognized as a subpopulation of CD4 + T cells with stem cell properties. Following phenotypical identification, we evaluated their level in patients during chronic HIV infection and following antiretroviral therapy (ART) using flow cytometry. The levels of CCR6 + CD95 + CD4 + T NA were decreased during chronic HIV infection and correlated with CD4 + T cell counts. Immunological responders harbored higher frequency of CCR6 + CD95 + CD4 + T NA , which was associated with CD4/CD8 T cell ratio. Immunological non-responders with lower frequency of CCR6 + CD95 + CD4 + T NA failed to exhibit a correlation between CCR6 + CD95 + CD4 + T NA and CCR6 + CD95 + CD4 + T CM , and displayed elevated ratio of CCR6 + CD95 + CD4 + T CM /T NA . The number of CCR6 + CD95 + CD4 + T NA was increased following early ART. These findings shed light on the importance of targeting pre-committed Th17 precursors that enhance immune reconstitution., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To describe the spectrum of central nervous system (CNS) disorders and the contribution of neurological immune reconstitution inflammatory syndrome (IRIS) in hospitalized HIV/AIDS patients in You'an Hospital, Beijing China., Study Design & Methods: A retrospective observational study conducted over a 24-month period in You'an Hospial, a public sector referral hospital in Beijing, China. This study enrolled HIV seropositive patients who were admitted for developing new or recurrent neurological and (or) psychiatric symptoms from September 2009 to August 2011. Medical records were reviewed, demographic and clinical data were collected. Patients with peripheral neuropathy and those in delirium were excluded from this study., Results: Of the total 620 HIV/AIDS hospital admissions from September 2009 to August 2011, 60 patients (9.7%) were hospitalized for CNS complications. The diagnosis of HIV infection was made after hospital admission in 16 of the 60 patients (26.7%), and 34 of them (56.7%) were already on antiretroviral therapy (ART) at the point of admission. The median CD4 cell count in these subjects was 39 (21-133) cells/mm(3), and 93.3% (56/60) of these patients belonged to stage IV HIV disease according to World Health Organization (WHO) classification. The most frequent diagnosis in these subjects included cryptococcal meningitis (CM, n=13, 22%), cerebral toxoplasmosis (n=10, 17%), and CNS tuberculosis (n=7, 11.7%). The overall mortality was 13% (8/60) and the case-fatality rates were: cryptococcal meningitis 7.7% (1/13), cerebral toxoplasmosis 20% (2/10) and tuberculous meningitis 28.6% (2/7). Of the 34 patients who were on ART, paradoxical neurological IRIS (the conditions of their existing CNS disorders get paradoxically worse after ART because of an exuberant inflammatory response directed towards opportunistic pathogens) was diagnosed in 4 patients (11.8%), 2 of whom related to TB infection (out of 5 TB patients, 40%), and the other 2 related to CM (out of 8 patients, 25%)., Conclusion: Opportunistic infections, such as cryptococcal meningitis, cerebral toxoplasmosis and CNS tuberculosis were the most frequent diagnosis of CNS disease in hospitalized HIV/AIDS patients in You'an Hospital, Beijing, China. About 10% patients on ART were diagnosed as neurological IRIS in such a group of patients., (Copyright © 2014 Elsevier B.V. All rights reserved.)