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Abstract The combination of ASC22, an anti-PD-L1 antibody potentially enhancing HIV-specific immunity and chidamide, a HIV latency reversal agent, may serve as a strategy for antiretroviral therapy-free virological control for HIV. People living with HIV, having achieved virological suppression, were enrolled to receive ASC22 and chidamide treatment in addition to their antiretroviral therapy. Participants were monitored over 24 weeks to measure changes in viral dynamics and the function of HIV-specific CD8+ T cells (NCT05129189). 15 participants completed the study. At week 8, CA HIV RNA levels showed a significant increase from baseline, and the values returned to baseline after discontinuing ASC22 and chidamide. The total HIV DNA was only transiently increased at week 4 (P = 0.014). In contrast, integrated HIV DNA did not significantly differ from baseline. Increases in the proportions of effector memory CD4+ and CD8+ T cells (TEM) were observed from baseline to week 24 (P = 0.034 and P = 0.002, respectively). The combination treatment did not succeed in enhancing the function of HIV Gag/Pol- specific CD8+ T cells. Nevertheless, at week 8, a negative correlation was identified between the proportions of HIV Gag-specific TEM cells and alterations in integrated DNA in the T cell function improved group (P = 0.042 and P = 0.034, respectively). Nine adverse events were solicited, all of which were graded 1 and resolved spontaneously. The combined treatment of ASC22 and chidamide was demonstrated to be well-tolerated and effective in activating latent HIV reservoirs. Further investigations are warranted in the context of analytic treatment interruption.

IntroductionIn the course of immune development, HIV-exposed uninfected (HEU) infants exhibit abnormal immune function and increased infectious morbidity compared to HIV-unexposed uninfected (HUU) infants. Yet the specific functional phenotypes and regulatory mechanisms associated with in-utero HIV and/or ART exposure remain largely obscure.MethodsWe utilized flow cytometry and RNA-seq technologies to conduct the immunological and transcriptomic profiling in cord blood from 9 HEU mother-infant pairs and 24 HUU pairs. On top of that, we compared the cord blood dataset with the maternal venous blood dataset to characterize unique effects induced by in-utero HIV and/or ART exposure.ResultsFlow cytometry immunophenotyping revealed that the level of B lymphocyte subsets was significantly decreased in HEU cord blood as compared to HUU (P < 0.001). Expression profiling-based cell abundance assessment, includes CIBERSORT and ssGSEA algorithm, showed a significantly reduced abundance of naive B cells in HEU cord blood (both P < 0.05), supporting the altered composition of B lymphocyte subsets in HEU. Functional enrichment analysis demonstrated suppressed innate immune responses and impaired immune regulatory function of B cells in HEU cord blood. Furthermore, through differential expression analysis, co-expression network analysis using WGCNA, and feature selection analysis using LASSO, we identified a 4-gene signature associated with HEU status. This signature effectively assesses B cell levels in cord blood, enabling discrimination between HEU and HUU infants.DiscussionOur study provides the first comprehensive immunological and transcriptomic characterization of HEU cord blood. Additionally, we establish a 4-gene-based classifier that holds potential for predict immunological abnormalities in HEU infants.

The study aimed to analyze changes in the clinical and epidemiological aspects of HIV-associated cryptococcal meningitis (CM) patients and to identify factors influencing their prognosis. Clinical data of patients with HIV-associated CM treated in Shanghai, China between 2013 and 2023 were collected. This study included 279 cases, 2.89% of AIDS patients, showing a yearly decrease in CM prevalence among AIDS patients (p < 0.001). Overall mortality was 10.39% with rates declining from a 2013 peak of 15.38% to 0% in 2023 despite no significant temporal pattern (p = 0.265). Diagnosis took an average of 18 ± 1 days post-symptoms, and admission CD4 counts averaged 29.2 ± 2.5 cells/μL, hinting at a non-significant decline. Frequent symptoms included fever (62.4%), headache (61.6%), fatigue (44.1%), and appetite loss (39.8%), with younger patients more likely to initially show signs of meningeal irritation. Logistic regression analysis underscored the prognostic importance of cerebrospinal fluid (CSF) white blood cell (WBC) count and procalcitonin levels. Over the decade spanning from 2013 to 2023, the incidence and mortality rates of CM among AIDS patients exhibited a downward trend. The average duration from the onset of CM to confirmation of diagnosis remained prolonged. CSF WBC count and procalcitonin levels were associated with unfavorable outcomes.

Granuloma is a crucial pathological feature of tuberculosis (TB). The relationship between CD4+ T cells in both peripheral blood and granulomatous tissue, and the integrity of granulomas in Human Immunodeficiency Virus (HIV)–MTB co-infection, remains unexplored. This study collected biopsy specimens from 102 TB patients (53 with HIV-MTB co-infection and 49 only with TB). Hematoxylin and eosin (HE) staining and immunohistochemical staining were performed, followed by microscopic examination of the integrity of tuberculous granulomas. Through statistical analysis of peripheral blood CD4+ T cell counts, tissue CD4+ T cell proportion, and the integrity of granulomas, it was observed that HIV infection leads to poor formation of tuberculous granulomas. Peripheral blood CD4+ T cell counts were positively correlated with granuloma integrity, and there was a similar positive correlation between tissue CD4+ T cell proportions and granuloma integrity. Additionally, a positive correlation was found between peripheral blood CD4+ T cell counts and the proportion of CD4+ T cells in granuloma tissues. Therefore, HIV infection could impact the morphology and structure of tuberculous granulomas, with a reduced proportion of both peripheral blood and tissue CD4+ T lymphocytes.

Abstract Introduction Cryptococcal meningitis (CM) is a serious and fatal fungal infection that affects individuals infected with human immunodeficiency virus (HIV). Despite treatment, recurrence of symptoms is common and could lead to poor outcomes. Corticosteroids are not always useful in treating symptom recurrence following HIV/CM; thus, alternative therapy is needed. Thalidomide has been reported to be effective in treating symptom recurrence in several patients with HIV/CM. This retrospective study aimed to investigate the efficacy and safety of thalidomide in the treatment of symptom recurrence following HIV/CM. Methods Patients who were treated with thalidomide for symptom recurrence following HIV/CM were retrospectively included. Clinical outcomes and adverse events were recorded and analyzed. Results Sixteen patients admitted between July 2018 and September 2020 were included in the analysis. During a median follow-up period of 295 (166, 419) days, all patients achieved clinical improvement in a median of 7 (4, 20) days. Among them, nine (56%) achieved complete resolution of symptoms at a median of 187 (131, 253) days, including 40% (2/5) of immune reconstitution inflammatory syndrome (IRIS), 50% (3/6) of patients with elevated ICP only, and 80% (4/5) of patients with symptoms only. Seven (43%) patients experienced nine episodes of adverse events, but no severe adverse event attributable to thalidomide was observed. None of the patients withdrew from thalidomide due to adverse events. Conclusion Thalidomide appears to be effective and safe in treating different types of symptom recurrence in HIV/CM. This study provides preliminary evidence supporting future randomized clinical trials to further investigate the efficacy and safety of thalidomide in treating symptom recurrence in this population.

Trends in and risk factors for drug resistance in Mycobacterium tuberculosis (M. tuberculosis) in human immunodeficiency virus (HIV)-infected patients with active tuberculosis were analyzed. The clinical data of M. tuberculosis and HIV-coinfected patients treated at the Shanghai Public Health Clinical Center between 2010 and 2022 were collected. The diagnosis of tuberculosis was confirmed by solid or liquid culture. The phenotypic drug susceptibility test was carried out via the proportional method, and the resistance to first-line and second-line drugs was analyzed. Logistic regression analysis was performed to identify associated risk factors for drug resistance in M. tuberculosis. Of the 304 patients with a M. tuberculosis-positive culture and first-line drug susceptibility test results, 114 (37.5%) were resistant to at least one first-line anti-tuberculosis drug. Of the 93 patients with first-line and second-line drug susceptibility test results, 40 (43%) were resistant to at least one anti-tuberculosis drug, and 20 (21.5%), 27 (29.0%), 19 (20.4%), 16 (17.2%), and 14 (15.1%) were resistant to rifampicin, streptomycin, ofloxacin, levofloxacin, and moxifloxacin, respectively; 17 patients (18.3%) had multidrug-resistant tuberculosis (MDR-TB). Between 2010 and 2021, the rate of resistance to streptomycin and rifampicin ranged from 14.3% to 40.0% and from 8.0% to 26.3%, respectively, showing an increasing trend year by year. From 2016 to 2021, the rate of resistance to quinolones fluctuated between 7.7% and 27.8%, exhibiting an overall upward trend. Logistic regression analysis showed that being aged p = 0.023; RR 7.734, p = 0.047; RR 3.733, p = 0.009). Retreatment tuberculosis was a risk factor for resistance to rifampicin, ofloxacin, of levofloxacin (RR 2.984, p = 0.047; RR 4.517, p = 0.038; RR 6.277, p = 0.014). The drug resistance rates of M. tuberculosis to rifampicin and to quinolones in HIV/AIDS patients were high and have been increasing year by year. Age and a history of previous anti-tuberculosis treatment were the main factors associated with the development of drug resistance in HIV/AIDS patients with tuberculosis.

BackgroundThe incidence of progressive multifocal leukoencephalopathy (PML) in people living with HIV (PLWH) is 2%-4%. Currently, there is no effective therapeutic strategy for the treatment of PML in PLWH, resulting in a mortality of up to 50%. This study aimed to identify risk factors of death and prognostic markers in people living with HIV with PML.MethodsA retrospective cohort study of AIDS-related PML individuals was conducted from January 1, 2015, to October 1, 2022, in Shanghai, China. PLWH who were diagnosed with PML for the first time were included. Kaplan-Meier curve and Cox regression were used to analyze the survival and its predictors. Levels of inflammatory markers and immune checkpoint inhibitors in blood and cerebrospinal fluid (CSF) were measured in the prestored samples using bead-based multiplex assay Indolamine 2,3-dioxygenase was determined using ELISA.ResultsTwenty of 71 subjects had initiated antiretroviral therapy (ART) before PML onset and no patients discontinued ART during this period. In total, 34 patients (47.9%) had opportunistic infections (OIs), the median CD4+ T cell count was 73.0 (33.0-149.0) cells/μL. The estimated probability of survival at six months was 78% (95% confidential intervals [CIs]:0.63-0.85). OIs, low CD4+ T cell count were associated with lower estimated six-month survival (hazard ratio 8.01, 95% CIs: 1.80-35.00, P=0.006 and 5.01, 95% CIs:1.57-16.03, p=0.007). Indolamine 2,3-dioxygenase activity in CSF of non-survivors group were higher than survivors group (p

Abstract Background Men who have sex with men (MSM) is a key population for preventing HIV in China, yet pre-exposure prophylaxis (PrEP) is not widely accepted in this population. The objective of this manuscript was to assessed the barriers in the acknowledgement and uptake focusing the demand side. Methods An online questionnaire survey was conducted from December 2018 to January 2019. All participants were required to scan two-dimensional code which was the online crowdsourcing survey platform to complete the electronic questionnaire anonymously. Results Among 1915 MSM from thirty-four cities of China, 512 (26.7%) versus 1617 (84.4%) had an objective or subjective need of PrEP, respectively. One hundred and six (5.5%) reported affordability and only 23 (1.2%) had ever taken it. Age, living alone and occupation were associated with the objective needs. Age, income, sexual behavior were associated with actual usage. The participants who they had objective need to use PrEP are the population which we should focus on. Conclusion A wide disconnect exists among the objective need, willingness, affordability and uptake of PrEP. Cost was the most prevalent barrier, accounting for 78.22% of individuals who needed and wished for PrEP but finally failed to receive it. The findings might facilitate optimizing future allocation of resources to better promote PrEP in Chinese MSM.

Objectives: Cross-reactivity with nontuberculous mycobacteria (NTM) species might limit the use of urine lipoarabinomannan (LAM) test to diagnose tuberculosis (TB) in people living with HIV (PLWH). This study aimed to investigate the utility of the LAM test among hospitalized HIV-positive patients. Methods: This prospective study enrolled HIV-positive inpatients with any TB symptom or seriously ill patients with advanced immunodeficiency. Urine samples were tested using the Alere Determine LAM Ag, and participants were categorized as confirmed TB, confirmed NTM infection, unclassified mycobacteria infection, and no mycobacteria infection based on microbiologic reference standards. Results: A total of 382 participants were included. The prevalence of confirmed TB and NTM infection was 5.24% (20 of 382) and 4.45% (17 of 382), respectively. The sensitivity and specificity of the urine LAM for TB diagnosis were 65.00% (95% confidence interval [CI] 40.78-84.61) and 89.36% (95% CI 85.68-92.36), respectively. The LAM test for NTM yielded a sensitivity of 58.82% (95% CI 32.92-81.56) and specificity of 88.61% (95% CI 84.87-91.70). Notably, the negative predictive values of the urine LAM for TB and NTM were 97.85% (95% CI 95.63-99.13) and 97.85% (95% CI 95.63-99.13), respectively. Conclusions: Cross-reactivity with NTM cause high false-positive LAM for TB diagnosis in PLWH. The correct identification of mycobacteria species is crucial for deciding treatment strategies.

Background: Rifamycins are the cornerstone of anti-tuberculosis therapy while they are potent inducers of drug metabolizing enzymes. For the first time, we evaluated the effect of rifampicin (RIF) and rifabutin (RBT) on the pharmacokinetics (PK) of dolutegravir (DTG) in patients with HIV and tuberculosis (TB)/ mycobacterium avium complex (MAC) co-infection. Methods: Both HIV/TB (or MAC) co-infected patients and HIV infected patients without TB/MAC were enrolled. Patients in the RIF group received DTG 50 mg twice daily together with 600mg of RIF, while patients in the RBT group received DTG 50 mg once daily together with 300 mg of RBT. The DTG pharmacokinetic profiles in different groups were assessed. Results: A total of 13 subjects in the RIF group, 12 subjects in the RBT group, and 10 subjects in non-TB/MAC group were enrolled. The geometric mean ratio (GMR) of the trough concentration (Ctr) of DTG in the RIF group to non-TB/MAC group was 1.33 [90% confidence interval (CI):0.97 to 1.81], while the GMR of the maximum concentration (Cmax) of DTG was 1.29 (90% CI: 1.23 to 1.36). The GMR of the Ctr of DTG in the RBT group to non-TB/MAC group was 0.41 (90% CI: 0.30 to 0.57), while the GMR of the Cmax of DTG was 0.55 (90% CI: 0.52 to 0.57). Conclusions: Due to the relatively low trough concentrations of DTG with RBT, DTG 50mg once daily together with RBT could only serve as an alternative option for HIV/TB (or MAC) co-infected patients.

Abstract Background Few data are available regarding the long-term case-fatality rate (CFR) among people living with HIV (PLWH) with nontuberculous mycobacteria (NTM) disease. The aim of this study is to analyze the long-term CFR in patients with NTM disease and to identify risk factors for their death. Methods A retrospective cohort study of 379 cases of microbiologically confirmed NTM disease in PLWH was conducted from January 1, 2012, to December 31, 2020, in Shanghai, China. We used Kaplan–Meier survival analysis and the log-rank test to compare the long-term CFR in patients with disseminated NTM (DNTM) and localized NTM disease. Univariate Cox proportional hazards regression analysis and a stepwise Cox proportional hazards regression model were used to estimate the predictors of long-term CFR. Results The cohort was followed up for a median of 26 months. The total CFR was 15.7% by one year and increased to 22.6% at 5 years after the diagnosis of NTM disease. The 5-year CFR of PLWH with DNTM was significantly higher than that of PLWH with localized NTM (26.7% vs 19.6% for DNTM and localized NTM disease, respectively). Older age [hazard ratio (HR) = 1.04, 95% confidence interval (CI): 1.02–1.06, P

Abstract Background Talaromyces marneffei (TM) bloodstream infection is common in Acquired Immunodeficiency Syndrome (AIDS) patients with extreme immunodeficiency in Southeast Asia and South China, however, clinical case study on TM bloodstream infection is scarce. We retrospectively analyzed the clinical characteristics of TM bloodstream infection in hospitalized AIDS patients and determined the outcomes of hospitalization after diagnosis in our hospital over the past 5 years. Methods From January 2015 to July 2020, 87 cases of TM detected by blood culture in patients admitted to our center were collected. The admission complaints, blood cells, biochemistry, CD4 and CD8 cell counts and 1,3-β-D-glucan (BDG), procalcitonin (PCT), CRP level on the day of blood culture test, and outcomes during hospitalization were analyzed. Logistic regression analysis was performed for the risk factors for poor prognosis (60 cases). Spearman correlation analysis was used to analyze the correlation between peripheral blood cells, albumin and the time required for TM turnaround in blood culture. The difference was statistically significant when the P value was 200/μl (p = 0.04), and those with BDG 100 pg/mL (p = 0.01). Conclusions TM bloodstream infection is becoming more common in advanced AIDS patients in endemic areas. For those patients with extremely low CD4 and CD8 cell counts below 200/μl is with an increased risk of poor prognosis.

Objectives: To evaluate the clinical utility of metagenomic next-generation sequencing (mNGS) for the diagnosis of central nervous system (CNS) infection in people living with human immunodeficiency virus (PLWH) in a real-world situation. Methods: Cerebrospinal fluid (CSF) was sent for mNGS for PLWH who tested negative on all conventional tests but were still suspected to have CNS infection. A retrospective analysis was undertaken of the results and the clinical effect of mNGS on this cohort. The final diagnosis was adjudicated by a panel discussion following hospital discharge when the results of all tests and patients’ responses to the empiric therapy were available. Results: Eighty-eight eligible PLWH, including 51 (58%) patients suspected of encephalitis and 34 (46.7%) patients suspected of meningitis, were included in the analysis. Sixty-eight (77.3%) patients were diagnosed with CNS infection, of which 50 were based on the pathogens identified by mNGS. The most common disease missed by mNGS was clinically suspected tuberculous meningitis, followed by clinically suspected non-tuberculous mycobacterial meningitis. The results from mNGS led to modification of treatment in 21 (23.9%) patients, and increased confidence in continuation of original therapy in 30 (34.1%) patients. During hospitalization, two (2.3%) patients died and 66 (75%) patients improved. Conclusions: mNGS of CSF is a useful tool for the diagnosis of CNS infection among PLWH. Further investigations are warranted to improve its sensitivity.

Abstract Aims Patients with COVID-19 can also have enteric symptoms. Here we analyzed the histopathology of intestinal detachment tissue from a patient with COVID-19. Methods The enteric tissue was examined by hematoxylin & eosin stain, PAS (Periodic acid–Schiff) staining, Gram staining, Ziehl–Neelsen stain and Grocott’s Methenamine Silver (GMS) Stain. The distribution of CD3, CD4, CK20 and CD68, cytomegalovirus (CMV) and Herpes Simplex Virus (HSV) antigen were determined by immunohistochemistry. In situ hybridization (ISH) of SARS-CoV-2 and Epstein-Barr virus-encoded small RNA (EBER) were also performed. Results We observed mucosal epithelium shedding, intestinal mucosal erosion, focal inflammatory necrosis with hemorrhage, massive neutrophil infiltration, macrophage proliferation accompanied by minor lymphocyte infiltration. Fungal spores and gram positive cocci but not mycobacteria tuberculosis were identified. Immunohistochemistry staining showed abundant CD68+ macrophages but few lymphocytes infiltration. HSV, CMV and EBV were negative. ISH of SARS-CoV-2 RNA showed positive signal which mostly overlapped with CD68 positivity. Conclusions The in situ detection of SARS-CoV-2 RNA in intestinal macrophages implicates a possible route for gastrointestinal infection. Further study is needed to further characterize the susceptibility of enteric cells to SARS-CoV-2 infection.

Abstract Background Tuberculosis (Tb) is the most frequent opportunistic infection among people living with HIV infection. The impact of Tb co-infection in the establishment and maintenance of the HIV reservoir is unclear. Method We enrolled 13 HIV-infected patients with microbiologically confirmed Tb and 10 matched mono-HIV infected controls. Total HIV DNA in peripheral blood mononuclear cells (PBMCs), plasma interleukin-7 (IL-7) concentrations and the activities of indoleamine 2,3-dioxygenase (IDO) were measured for all the participants prior to therapy and after antiretroviral therapy (ART). Results After a duration of 16 (12, 22) months’ ART, patients co-infected with Tb who were cured of Tb maintained higher levels of HIV DNA compared with mono-HIV infected patients [2.89 (2.65- 3.05) log10 copies/106 cells vs. 2.30 (2.11–2.84) log10 copies/106 cells, P = 0.008]. The levels of on-ART HIV DNA were positively correlated with the baseline viral load (r = 0.64, P = 0.02) in Tb co-infected group. However, neither plasma IL-7 concentration nor plasma IDO activity was correlated with the level of on-ART HIV DNA. Conclusions Tb co-infection was associated with the increased surrogate marker of the HIV reservoir, while its mechanism warrants further examination.

ABSTRACTReduced doses of antiretroviral (ARV) drugs may lower toxicity while preserving efficacy. We aimed to evaluate the efficacy of reduced doses of both tenofovir disoproxil fumarate (TDF) and efavirenz for the treatment of HIV-1 infection. In this open-label, non-inferiority trial, HIV-1-infected antiretroviral-naive adults were randomly assigned to receive either a lower dose anti-retroviral regimen comprised of TDF (200 mg), efavirenz (400 mg), and standard dose lamivudine (300 mg) or the standard dose regimen. The primary endpoint was the proportion of participants with HIV-1 RNA≤ 50 copies/mL at week 48 using a non-inferiority margin of –10%. At week 48, 79 of 92 (85.9%) participants in the lower dose regimen group and 78 of 92 (84.8%) in the standard dose regimen group achieved HIV-1 RNA≤ 50 copies/mL (treatment difference 1.1%, 95% CI −9.1 to 11.3) in the intention-to-treat analysis. Drug-related adverse events occurred more frequently in the participants receiving the standard dose regimen compared with the lower dose one (63.0% vs 80.4%). Changes in estimated glomerular filtration rate and bone mineral density were comparable between the two groups. The non-inferior efficacy and better safety profile of the lower dose ARV regimen support its use as alternative initial therapy for HIV-1 infected patients.

PurposeTo investigate the sensitivity of SARS-CoV-2 testing in specimens collected from the anterior nasal vestibules of COVID-19 patients.MethodsA cross-sectional analysis was performed on 30 patients with a confirmed diagnosis of COVID-19 at the Shanghai Public Health Clinical Center from March 14, 2020 to March 21, 2020. Paired specimens were collected from both the anterior nasal vestibule and the oropharynx from all patients. All specimens were tested for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR) assays.ResultsOf the 30 patients with confirmed COVID-19, 17 patients (56.7%) tested positive for SARS-CoV-2 when oropharyngeal specimens were used, while 20 patients (66.7%) tested positive when nasal swab specimens were used. There was no statistically significant difference in sensitivity between the two methods.ConclusionsRespiratory swabs collected from the nasal vestibule offer a less invasive alternative to oropharyngeal swabs for specimen collection in the detection of SARS-CoV-2 infection, and have adequate sensitivity.

Dysregulation of immune response was observed in COVID-19 patients. Thymosin alpha 1 (Tα1) is used in the management of COVID-19, because it is known to restore the homeostasis of the immune system during infections and cancers. We aim to observe the longitudinal changes in T lymphocyte subsets and to evaluate the efficacy of Tα1 for COVID-19. A retrospective study was conducted in 275 COVID-19 patients admitted to Shanghai public health clinical center. The clinical and laboratory characteristics between patients with different T lymphocyte phenotypes and those who were and were not treated with Tα1 were compared. Among the 275 patients, 137 (49.8%) were males, and the median age was 51 years [interquartile range (IQR): 37-64]. A total of 126 patients received Tα1 therapy and 149 patients did not. There were 158 (57.5%) patients with normal baseline CD4 counts (median:631/μL, IQR: 501~762) and 117 patients (42.5%) with decreased baseline CD4 counts (median:271/μL, IQR: 201~335). In those with decreased baseline CD4 counts, more patients were older (p

Background: Tenofovir disoproxil fumarate (TDF) is an important component of antiretroviral therapy (ART) that has been widely used. The aim of this study was to observe the long-term impact of TDF-based ART on lipid metabolism profiles and renal functions in Chinese patients. Methods: 414 and 124 HIV-infected, ART-naïve patients who initiated TDF-based regimens and non-TDF regimens respectively were retrospectively included. Demographic characteristics and clinical information of each patient was collected. Changes of lipid profiles and renal function, as well as the risk factors of hyperlipidemia and renal dysfunction were analyzed. Results: After 96 weeks of ART, HIV viral loads were undetectable in 97.34% (403/414) of patients exposed to TDF. The plasma total cholesterol (TCH) increased from 3.97 ± 0.83 mmol/L to 4.53 ± 0.87 mmol/L (P

Objectives: The purpose of this study was to investigate the clinical features and related laboratory indicators of cytomegalovirus retinitis in HIV infected patients in order to find a suitable laboratory reference guide to aid in the early diagnosis of CMVR, which should improve the prognosis of the severe retinitis.Methods: PLHIVs who were admitted to our hospital from January 2010 to December 2016 were included. The diagnosis of AIDS follows the AIDS Treatment Guidelines. Levels of CMV IgG and IgM were measured by ELISA in order to detect the CMV infection status of the patient. CMV-DNA levels were assessed by a quantitative PCR method, and CD4+ T lymphocytes were detected by flow cytometry. Logistical regression was used to analyze the risk factors for CMV retinitis in HIV-infected patients.Results: There were 93 patients with HIV that were also diagnosed with CMV retinitis. After ART, the intraocular pressure, visual acuity, cotton plaque incidence, and CD4+ T lymphocyte count were significantly improved, and the yellow-white retinal lesions gradually disappeared. In patients with HIV infections, the CD4+ T lymphocyte count, and peripheral blood quantitative CMV-DNA levels were found to be independent risk factors for CMV retinitis (P < 0.05). Patients with HIV infection who had CMV-DNA levels >6,390 copies/mL were associated with more severe ophthalmolgic conditions related to CMV retinitis.Conclusion: Patients with HIV infections with quantitative CMV-DNA levels >6,390 copies/mL have a higher probability of having a diagnosis of CMV retinitis and a worse prognosis than those whose CMV-DNA level is

The purpose of this study was to identify fecal bacterial microbiome changes in patients with chronic human immunodeficiency virus (HIV) infection in China. Bacterial 16S rRNA genes were amplified, sequenced (454 pyrosequencing), and clustered into operational taxonomic units using the QIIME software. Relative abundance at the phylum and genus levels were calculated. Alpha diversity was determined by Chao 1 and observed-species indices, and beta diversity was determined by double principal component analysis using the estimated phylogeny-based unweighted Unifrac distance matrices. Fecal samples of the patients with chronic HIV-infection tended to be enriched with bacteria of the phyla Firmicutes (47.20%±0.43 relative abundance) and Proteobacteria (37.21%±0.36) compared with those of the non-HIV infected controls (17.95%±0.06 and 3.81%±0.02, respectively). Members of the genus Bilophila were exclusively detected in samples of the non-HIV infected controls. Bacteroides and arabacteroides were more abundant in the chronic HIV-infected patients. Our study indicated that chronic HIV-infected patients in China have a fecal bacterial microbiome composition that is largely different from that found in non-HIV infected controls, and further study is needed to evaluate whether microbiome changes play a role in disease complications in the distal gut, including opportunistic infections.Emerging Microbes & Infections (2016) 5, e31; doi:10.1038/emi.2016.25; published online 6 April 2016Chinese patients with chronic HIV exhibit clear differences in their gut microbe populations compared with healthy controls. Infections and illness, along with the drugs used to treat them, can change the natural microbial ecosystem in the gut, which varies not just from person to person but also between ethnic groups. To investigate gut microbe diversity in the Chinese population, Hong-zhou Lu at Fudan University, Shanghai, together with Ben Li at Shanghai TargetDrug Ltd and co-workers, conducted a small-scale genetic sequencing study of microbial diversity in the feces of 13 patients with HIV and four healthy controls. The HIV-infected individuals exhibited significant differences compared with the controls, including reduced microbial diversity and higher levels of certain bacteria. Further investigations could clarify the role of this diversity in disease complications, and enhance understanding of differences between ethnic groups.

To investigate the reasons and risk factors for modification of the first combined antiretroviral therapy (cART) currently used for HIV infected patients who were treatment naïve in Shanghai China.Making a retrospective observational research on treatment naïve patients with HIV infection who initiated cART during the period of September 1st 2005---December 1st 2013. The demographic and clinical data were collected from the first visit to the time of the first regimen modification or the last visit in December 1st, 2014. The reasons of treatment modification were recorded. Survival analysis of modification was made by Kaplan-Meier curves analysis and log rank test, and a Cox multiple regression model was constructed to identify related factors of modification.A total number of the eligible participants were 3372 and 871(25.8%) patients changed their first cART regimen. The median follow up was 22 months [interquartile range (IQR) 14-39]. Among patients who modified the original regimen, drug toxicity occurred in 805(92.4%) participants and 44(5.1%) experienced treatment failure. In multiple regression analysis regimen modification was associated with patients' age more than 40 years old (aHR 1.224, 95%CI 1.051-1.426, P = 0.010), CD4 less than 200(aHR 1.218, 95%CI 1.044-1.421, P = 0.012) and the initial regimen they received. Compared with the regimen of TDF+3TC+EFV, patients with regimen of d4T+3TC+NVP, d4T+3TC+EFV, AZT+3TC+NVP or AZT+3TC+EFV were 10.4, 8.2, 6.4, 2.5 times more likely to modify their initial regimen, respectively.The main reason for the regimen switch was drug toxicity and main risk factors for regimen modification were age older than 40 years, CD4 cell counts less than 200 at baseline and regimen they received. Among the 2NRTI plus 1NNRTI regimens, the co-formulation of d4T+3TC+NVP had the highest risk for modification while the regimen of TDF+3TC+EFV was the most tolerable treatment regimen in first years' follow up.

Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, catabolizes tryptophan to kynurenine and other downstream catabolites. It is known to be an immune mediator in HIV pathogenesis. The impact of anti-retroviral therapy on its activity has not been well established.We measured systemic IDO activity (the ratio of plasma kynurenine to tryptophan) in HIV-infected patients before and after highly active antiretroviral therapy (HAART) and its association with a microbial translocation marker, soluble CD14 (sCD14).Among 76 participants, higher baseline IDO activity was associated with lower CD4+ T cell counts (P

BackgroundInterferon-gamma release assays (IGRAs) have provided a new method for the diagnosis of Mycobacterium tuberculosis infection. However, the role of IGRAs for the diagnosis of active tuberculosis (TB), especially in HIV-infected patients remains unclear.MethodsWe searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001-July 2011 that evaluated the evidence of using QuantiFERON-TB Gold in-tube (QFT-GIT) and T-SPOT.TB (T-SPOT) on blood for the diagnosis of active TB in HIV-infected patients.ResultsThe search identified 16 eligible studies that included 2801 HIV-infected individuals (637 culture confirmed TB cases). The pooled sensitivity for the diagnosis of active TB was 76.7% (95%CI, 71.6-80.5%) and 77.4% (95%CI, 71.4-82.6%) for QFT-GIT and T-SPOT, respectively, while the specificity was 76.1% (95%CI, 74.0-78.0%) and 63.1% (95%CI, 57.6-68.3%) after excluding the indeterminate results. Studies conducted in low/middle income countries showed slightly lower sensitivity and specificity when compared to that in high-income countries. The proportion of indeterminate results was as high as 10% (95%CI, 8.8-11.3%) and 13.2% (95%CI, 10.6-16.0%) for QFT-GIT and T-SPOT, respectively.ConclusionIGRAs in their current formulations have limited accuracy in diagnosing active TB in HIV-infected patients, and should not be used alone to rule out or rule in active TB cases in HIV-infected patients. Further modification is needed to improve their accuracy.

Background: Human Immuno-deficiency Virus (HIV) associated non-Hodgkin's lymphoma (NHL) was a special group of disease, which manifests distinct clinical features and prognosis as compared with NHLs in patients without HIV. We performed this study to describe the clinical features of the disease and investigated the potential prognostic factors. Methods: HIV-infected patients who were newly diagnosed with NHL were enrolled in this study. The selection of anti-lymphoma treatment regimen was mainly dependent on the pathological subtypes of NHLs. Tumor response was reviewed and classified according to the International Workshop Criteria. Results: A total of 78 patients were enrolled, among whom, 42 (53.8%) were with Diffuse large B cell Lymphoma (DLBCL), and 29 (37.2%) were with Burkitt lymphoma (BL). BL patients presented with higher risk features as compared with DLBCL in terms of numbers of extranodal diseases (P = 0.004) and poor Eastern cooperative oncology group (ECOG) score (P = 0.038). The estimated 2-year overall survival (OS) and progression free survival (PFS) rate was 74.3 ± 8. 1%, 28.9 ± 11.0%, and 54.2 ± 8.1%, 19.2 ± 7.5% for DLBCL and BL, respectively. In multivariate analysis, international prognostic index (IPI) score was an independent prognostic factor for predicting both OS (OR = 2.172, 95% CI 1.579-2. 987, P < 0.001) and PFS (OR = 1.838, 95% CI 1.406-2.402, P < 0.001). Conclusions: HIV associated NHLs represents a group of heterogeneous aggressive diseases with poor prognosis. IPI parameters were still effective in predicting the prognosis of HIV associated NHLs. [ABSTRACT FROM AUTHOR]

Meningitis caused by non-tuberculous mycobacteria (NTM) has a low incidence and is a rare form of NTM infection. In an increasing number of cases, however, disseminated mycobacterial infection is noted in acquired immune deficiency syndrome (AIDS). Described here are two patients with AIDS who were infected with NTM. Both patients eventually died, but one did receive anti-NTM treatment. Non-tuberculous mycobacterial meningitis must be suspected in patients with AIDS who present with prolonged fever and brain symptoms, and anti-NTM drugs should be promptly administered if necessary. [ABSTRACT FROM AUTHOR]

Background: The immunologic status of a newly diagnosed HIV positive population in the era of antiretroviral therapy in China has not been extensively evaluated. We conducted a cross-sectional survey to evaluate the CD4 counts of newly diagnosed HIV-infected persons and determine the factors influencing these counts in China. Methods: Two thousand eight hundred and sixty-six newly diagnosed HIV-infected patients from 10 provinces in China were selected during 2009 to 2010. Serum samples were collected to measure CD4 counts by flow cytometry. Demographics and medical histories were recorded. Multivariate logistic regression models were used to analyze factors associated with low CD4 count (<100 cells/mm3) at HIV diagnosis. Results: Among the 2866 patients, 2159 (75.33%) were male. Mean age was 40 years (range: 18-86 years). The median CD4 count at HIV diagnosis was 83 cells/mm3, 72.02% of the patients had a CD4 count that was ⩽200 cells/mm3, 53.98% had CD4 counts <100 cells/mm3. The difference in CD4 counts between males and females was not statistically significant (P=0.469). The median CD4 count differed significantly according to age (P=0.002), province (P<0.001), ethnicity (P<0.001) and HIV transmission route (P<0.001). In multivariate logistic analysis, factors associated with greater odds of low CD4 count at HIV diagnosis included male sex, younger age, HIV transmission route classified as unknown transmission risk, having been diagnosed in provinces Guangxi, Henan, Heilongjiang, Jiangxi, Shanghai and Yunnan. Conclusions: At the time of HIV diagnosis, a large proportion of HIV-infected patients in China had an initial CD4 count that was consistent with relatively advanced disease. Low CD4 count was associated with male gender, younger age, route of HIV transmission and geographical areas. HIV testing policy that promotes routine testing for HIV infection is needed to facilitate earlier HIV diagnosis. [ABSTRACT FROM AUTHOR]

Background: The human immunodeficiency virus type 1 (HIV-1) pandemic has continued unabated for nearly 30 years. To better understand the influence of virus on host cells, we performed the differential proteome research of peripheral blood mononuclear cells (PBMCs) from HIV-positive patients and healthy controls. Results: 26 protein spots with more than 1.5-fold difference were detected in two dimensional electrophoresis (2DE) gels. 12 unique up-regulated and one down-regulated proteins were identified in HIV-positive patients compared with healthy donors. The mRNA expression of 10 genes was analyzed by real time RT-PCR. It shows that the mRNA expression of talin-1, vinculin and coronin-1C were up-regulated in HIV positive patients and consistent with protein expression. Western blotting analysis confirmed the induction of fragments of vinculin, talin-1 and filamin-A in pooled and most part of individual HIV-positive clinical samples. Bioinformatic analysis showed that a wide host protein network was disrupted in HIV-positive patients. Conclusions: Together, this work provided useful information to facilitate further investigation of the underlying mechanism of HIV and host cell protein interactions, and discovered novel potential biomarkers such as fragment of vinculin, filamin-A and talin-1 for anti-HIV research. [ABSTRACT FROM AUTHOR]

In the context of an aging global population, the aging of patients with HIV is an issue that society will have to face. Data indicate that between 2011 and 2019, the proportion of patients age 60 and over who were newly diagnosed with HIV in China increased from 12% to 25%. In contrast to younger groups, the special characteristics of older patients pose major challenges to the management of their disease. The current study examined the clinical outcomes and psychological status of patients age 50 and over who were diagnosed with HIV. Out of a total of 566 older patients from eastern China, viral suppression was achieved in 446 (78.8%), treatment was immunologically effective in 410 (72.4%), and treatment was effective in 324 (57.2%). Thirty-nine patients (6.9%) had significant anxiety and 143 (25.3%) exhibited depressive tendencies. Level of education and the time from diagnosis to treatment were associated with the effectiveness of treatment. Age, sleep quality, chronic illness, exercise, and travel time to medical appointments were associated with depressive symptoms. These findings suggest that the burden of HIV among the older population remains high in more economically developed areas. The urgent need for HIV education and screening programs, as well as follow-up visits and early initiation of treatment in older patients, is called for. [ABSTRACT FROM AUTHOR]

The precise role of indoleamine 2,3-dioxygenase (IDO) in cardiovascular diseases (CVD) among people living with HIV (PLWH) is still under debate, despite recognized links. This study aimed to investigate the impact of elevated IDO activity on endothelial dysfunction in PLWH. A total of 38 PLWH, who had not previously received anti-retroviral therapy (ART), were enrolled in the study. These participants were monitored for 36 months following the initiation of ART. Measurements including plasma levels of IDO activity, markers of endothelial dysfunction, inflammatory factors, and lipids. In vitro, human aortic endothelial cells (HAEC) were exposed to interferon-γ, an IDO inhibitor, a kynurenine 3-hydroxylase (KMO) inhibitor, as well as different concentrations of kynurenine. Pre-ART, PLWH demonstrated notably elevated plasma concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1(sVCAM-1), and IDO activity in comparison to healthy controls. Post-ART, both IDO activity and sICAM-1 levels experienced a significant decrease, with IDO activity reaching levels comparable to those observed in healthy controls. Furthermore, a positive correlation was observed between IDO activity and sICAM-1 (p = 0.0002), as well as sVCAM-1 (p < 0.0001) before ART. In vitro, the augmentation of kynurenine concentration in the medium and the induction of IDO expression in HAEC resulted in increased production of reactive oxygen species (ROS), with minimal impact on endothelial dysfunction. From these findings, it can be concluded that long-term ART has the potential to restore the heightened IDO activity observed in PLWH. The overexpression of IDO primarily influences the expression of ROS in HAEC. [ABSTRACT FROM AUTHOR]

We retrospectively reviewed the medical records of 17 fatal H7N9 cases in Shanghai in 2013, analyzed clinical variables and described their clinical and epidemiologic characteristics. The median age was 73 years, and 82.4% had underlying medical conditions. The most frequent symptoms were fever (100%), followed by productive cough (47.1%) and dry cough (35.5%). Thirteen (76.5%) patients had dyspnea or respiratory distress, five (29.4%) had shock, and four (23.5%) had acute kidney injury. Seventeen (100.0%) patients had lymphopenia. Involvement of both lungs was found by chest radiography in 14 (82.4%) patients at presentation. Fifteen (88.2%) patients were hospitalized. The median times from illness onset to hospitalization and to diagnosis confirmation were both six days. Eleven (64.7%) patients were admitted to the intensive care unit. Sixteen (94.1%) patients were treated with oseltamivir. The median time from illness onset to oseltamivir treatment was six days. Among six patients for whom the duration of viral shedding was available, the median duration of viral shedding after oseltamivir treatment was 17 days. The median time from illness onset to death was 11 days. Refractory hypoxemia accounted for most deaths. The clinical and epidemiologic characteristics in the Shanghai fatal series of patients do not differ from other reports of H7N9 patients in China. This investigation reflects a delay in the diagnosis and antiviral treatment of H7N9 patients in the early stage of the epidemic in Shanghai. Late antiviral treatment and a long duration of viral shedding may be associated with a fatal outcome in these patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Globally, the overall mortality rate among HIV-infected patients has significantly declined during the HAART era. Deaths among HIV-infected inpatients need to be characterized in order to formulate intervention strategies to further improve medical care for this population and their prognosis. In the current study, deaths among HIV-infected inpatients from 2006 to 2015 at a medical center for HIV infection and AIDS patient care in Shanghai, China were retrospectively analyzed. Trends in mortality rates and the proportion of deaths caused by AIDS or non-AIDS-related illnesses were evaluated. A bivariate analysis was performed to identify the demographic and clinical factors associated with AIDS or non-AIDS-related deaths among HIV-infected inpatients. Among 6,473 HIV-infected patients who were discharged from 2006 to 2015, 326 deaths (5.04%) were identified. The yearly mortality rate declined significantly over time (χ2 = 34.41, p < 0.001). Results revealed that most deaths were attributed to AIDS-related illnesses (76.9 %, 233/303), and the proportion of causes of death did not change significantly over time (χ2 = 13.847, p = 0.127). Bivariate analysis identified characteristic factors associated with AIDS-related mortality. Compared to patients who died of non-AIDS illnesses, patients who died of AIDS-related illnesses had a CD4+ T cell count lower than 50 cells/μL (OR 4.587, 2.377-8.850) and fewer liver (OR 0.391, 0.177-0.866) or renal comorbidities (OR 0.188, 0.067-0.523) on admission. Results indicated that the overall in-hospital mortality rate among HIV-infected patients has declined over the past decade. However, AIDS-related illnesses were still the major causes of deaths among HIV-infected inpatients, suggesting that further efforts are needed to improve AIDS care in China. [ABSTRACT FROM AUTHOR]

We conducted a cross-sectional study to determine the prevalence and risk factors of leukopenia and thrombocytopenia among Chinese adults with newly diagnosed HIV/ AIDS. One thousand nine hundred and forty-eight newly diagnosed HIV-infected patients were enrolled between 2009 and 2010. Serum samples obtained from each individual were collected for complete blood count. Factors associated with the presence of leukopenia and thrombocytopenia were analyzed by multiple logistic regression. The overall prevalence of leukopenia and of thrombocytopenia was 33.2% and 15.6%, respectively. The prevalence of leukopenia was higher among females than among males (39.4% versus 31.2%). The prevalence of leukopenia increased with decreasing CD4 count (8.2%, 26.5%, 33.4%, and 41.5% among patients with CD4 count of ⩾ 350, 200-349, 50-199, and < 50 cells/mm3 respectively). The prevalence of thrombocytopenia also showed an increasing trend with decreasing CD4 count (5.8%, 12.2%, 17.8%, and 17.5% among patients with CD4 count of ⩾ 350, 200-349, 50-199, and < 50 cells/mm3, respectively). Logistic analysis showed that female sex, lower CD4 count, and Han ethnicity were significantly associated with an increased risk of leukopenia, and that lower CD4 count, and HIV transmission by blood were significantly associated with an increased risk of thrombocytopenia. The study reflects that leukopenia and thrombocytopenia are common among Chinese adults with newly diagnosed HIV/AIDS; and lower CD4 count is associated with an increased risk of both leukopenia and thrombocytopenia. We propose that a routine assessment of these parameters is necessary for timely and adequate clinical management. [ABSTRACT FROM AUTHOR]

The increased co-incidence of tuberculosis (TB) and AIDS is compounded by the emergence of opportunistic infections with non-tuberculous mycobacteria (NTM) in patients with HIV/ AIDS, and the treatment for these infections differs from that for TB. The high frequency of NTM strains found in patients infected with HIV raises concerns about accurate species identification before deciding proper treatment. A total of 101 isolates from 2014, 137 from 2015, and 162 from 2016 were subjected to 16S rDNA sequencing to identify the species. Forty-one (41/101, 40.6%) were identified as NTM in 2014, 64 (64/137, 46.7%) were identified as NTM in 2015, and 72 (72/162, 44.4%) were identified as NTM in 2016 in Chinese patients infected with HIV. The species of Mycobacteria isolates needs to be rapidly and accurately identified to determine appropriate antibiotic therapy, and this is especially true for patients infected with HIV. [ABSTRACT FROM AUTHOR]