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OBJECTIVES People living with HIV (PLWH) have a high risk of kidney injury. Measurement of serum creatinine, along with proteinuria, is not sensitive to detect early kidney injury. Here, we investigated novel urinary biomarkers of early renal injury in PLWH. METHODS We performed a cross-sectional study of 166 antiretroviral-naive PLWH and 99 HIV-negative persons who all had an estimated glomerular filtration rate > 90 mL/min/1.73 m2 . We compared the levels of seven urinary biomarkers between the two groups using the propensity score matching (PSM) approach and explored the risk factors associated with elevated urinary biomarkers in PLWH. RESULTS Eighty-three pairs were successfully matched based on PSM. Compared with the HIV-negative group, the HIV-positive group had higher ratios of N-acetyl-β-D-glucosaminidase (NAG) to urine creatinine (UCr), alpha1-microglobulin (α1-M) to UCr, kidney injury marker-1 (KIM-1) to UCr, neutrophil gelatinase-associated lipocalin to UCr, and epidermal growth factor to UCr, whereas the Tamm-Horsfall protein to UCr ratio and the abnormal albumin to UCr ratio were not significantly different. Positive correlations were observed between HIV RNA level and NAG: UCr (rs = 0.32; P

The objective of this study was to evaluate whether combination antiretroviral therapy (cART) has an effect on the clinical manifestations, radiological characteristics, and disease severity of human immunodeficiency virus (HIV)-associated Talaromyces marneffei infection. The clinical manifestations, chest computed tomography (CT) images, and disease severity were compared between 14 patients with culture-confirmed T. marneffei infections who received cART and 38 patients who did not receive cART. Clinical manifestations included high fever (>38°C), cough, shortness of breath, chills, and skin rash. Chest CT scans were evaluated for the presence of ground-glass opacities, consolidation, miliary nodules, nodules, masses, cavitation, pericardial effusion, pleural effusion, mediastinal lymphadenitis, and the distribution of parenchymal abnormalities. Disease severity was estimated by clinical manifestations and chest CT findings. Fever (>38°C), cough, shortness of breath, and chills were significantly less frequent in patients who received cART than in those who did not receive cART (P

Reduced 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 (pvs 11, p=0.028) and the decreased baseline CD4 counts group (15 vs 11, p=0.008), duration of virus clearance in the patients with Tα1 therapy was significantly longer than that in those without Tα1 therapy. There was no significant difference in the increase of CD4+ (286 vs 326, p=0.851) and CD8+ T cell (154 vs 170, p=0.842) counts in the recovery period between the two groups with or without Tα1 therapy. Multivariate linear regression analysis showed that severity of illness (p

Background:Due to the persistence of latent HIV-infected cellular reservoirs, HIV virus can not be eradicated completely.Objective:To identify proteins related to HIV latency, we performed a subcellular proteomic study in HIV latent cell lines.Method:An established HIV-1 latent cell model (J-Lat Tat-GFP Clone A7 cells, A7 cells) and its parental cell line (Jurkat cells) were used. The plasma membrane (PM) fraction from cultured cells was enriched through aqueous two-phase partition. PM proteins were extracted and then separated using two-dimensional electrophoresis (2DE). Differentially expressed proteins were identified by mass spectrometry, and verified by western blotting.Results:Thirteen non-redundant proteins were identified to be differentially expressed in the A7 PM fraction compared to those in the Jurkat PM. Eight had a PM location through Gene Ontology (GO) analysis. A differential protein network of CAPG-ACTR3-CD3D was detected to have interactions with HIV Vpr, Tat, gp160, etc. through STRING software analysis. One of the differential proteins (Macrophage-capping protein (CAPG)) was verified by western blotting to be down- regulated in two cell lines and HIV resting CD4+ T cells negatively selected from patients.Conclusion:We identified 13 proteins in A7 compared to Jurkat cells. CAPG may be a potential biomarker related to HIV latency.

Introduction Lymphoma is the most common cancer in HIV/AIDS patients. Chemotherapy regiments recommended for lymphomas in HIV-negative patients are also used for lymphomas in HIV/AIDS patients. Little is known about the infections among HIV/AIDS patients with lymphoma undergoing chemotherapy. Methods This retrospective study investigated the incidence, spectrum of and risk factors for infections during chemotherapy in 164 HIV/AIDS patients with lymphoma admitted to Shanghai Public Health Clinical Center from July 2013 to December 2020. Results The median age of the patients was 43 years old; 90.9% (149/164) were male. A total of 112 (68.3%) patients had a CD4 count < 200 cells/μL at lymphoma diagnosis. Diffuse large B-cell lymphoma (56%, 91/164) and Burkitt lymphoma (28%, 46/164) were the two most common subtypes of lymphoma. Among the 137 patients who underwent chemotherapy (total cycles = 749), 58.4% (80/137) of patients experienced a total of 153 episodes of infection, with an incidence rate of 20.4% (153/749). The most commonly seen infections were lung infection (29.2%, 40/137) and febrile neutropenia (27.0%, 37/137). Multivariate analysis showed that grade 4 neutropenia during chemotherapy (OR = 7.128, 95% CI 3.051-16.654, p < 0.001) and duration of antiretroviral treatment at lymphoma diagnosis

BACKGROUND: To investigate the temporal pattern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presence on ocular surfaces using conjunctival swabs in coronavirus disease 2019 (COVID-19) patients. METHODS: This study included 59 patients (32 newly admitted and 27 hospitalized for ≥2 weeks) with a COVID-19-confirmed diagnosis at the Shanghai Public Health Clinical Center from March 3, 2020, to March 21, 2020. Conjunctival swab samples were collected from both eyes of all the 59 patients and were tested by reverse transcription polymerase chain reaction (RT-PCR) assay. The range of sampling time lies widely between 1 and 50 days since symptom onset. RESULTS: Among the 32 newly admitted patients, positive RT-PCR results for SARS-CoV-2 in conjunctival swab samples were reported in 2 patients (one eye for each) without ocular discomfort, but 1 positive case had conjunctival congestion. The positive results were detected on Day 5 for 1 patient and Day 7 for the other, but repeated tests after 1 week were negative for both patients. All 27 patients who had been hospitalized for ≥2 weeks had negative test results. The mean time from symptom onset to sampling of 2 positive cases was significantly less than that of 57 negative cases (P

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.

OBJECTIVES Tuberculosis (TB) is the most common and fatal opportunistic co-infection among HIV-infected individuals. While TB-associated mortality predominantly occurs in the first 90 days after admission, such a correlation remains unclear in HIV/TB co-infected patients. Thus, we aimed to investigate the 90-day mortality and associated risk factors among HIV/TB co-infected patients in China. METHODS Adult patients with HIV and a newly confirmed TB diagnosis admitted to the Shanghai Public Health Clinical Center between September 2009 and August 2017 were enrolled. Clinical and laboratory characteristics, key treatments and outcomes were collected retrospectively. The associations between different factors and early mortality were analysed. RESULTS Of the 485 laboratory-confirmed HIV/TB patients [median (range) age = 39 (19-79) years], 413 (85.15%) were male. Diagnosis was confirmed by culture, pathology and acid-fast bacilli smear alone in 362 (74.6%), 6 (1.2%) and 117 (24.1%) patients, respectively. Multiple drug-/rifampin-resistant TB was detected in 21 (5.8%) of the 367 patients with a positive culture. Rifampin or rifabutin was administered to 402 (82.9%) patients. Additionally, 66 (13.6%) and 86 (17.7%) died within 90 days and 1 year of admission, respectively. Of the 64 TB-related deaths, 59 (92.2%) occurred within 90 days of admission. In Cox regression, central nervous system (CNS) TB [odds ratio (OR) = 2.49, 95% confidence interval (CI): 1.46-4.23, P

BackgroundTuberculosis (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.MethodWe 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).ResultsAfter 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) log10copies/106cells vs. 2.30 (2.11–2.84) log10copies/106cells,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.ConclusionsTb co-infection was associated with the increased surrogate marker of the HIV reservoir, while its mechanism warrants further examination.

Background Metabolic syndrome becomes a focus of clinical cares to people living with HIV (PLHIV) globally. This study aimed to explore the metabolic profiles in cerebrospinal fluid (CSF) of Chinese people living with HIV (PLHIV). Methods Cerebrospinal fluid samples from PLHIV and healthy controls were collected from our hospital. Then, the metabolic profiles of CSFs were analyzed PLHIV with healthy individual as the normal controls using the untargeted GC/TOFMS. Following this, kyoto encyclopedia of genes and genomes annotation and pathway analysis were performed to further explore the underlying mechanism of these metabolic alterations in cognitive impairment of PLHIV. Results Both PCA analysis and OPLS‐DA had presented that most samples were localized in 95% CI and the gap between control and HIV could significantly separate from each other. Upon this quality control, a total of 82 known metabolites were identified in CSF between PLHIV and healthy controls. Clustering of these metabolites presented that these differentially expressed metabolites could markedly distinguish HIV from healthy controls. Further pathway analyses showed that TCA cycle (citric acid, fumaric acid, lactate, et al.), amino acid (arginine, proline, alanine, aspartate, glutamine, et al.), lipid (cholesterol, butyrate, et al.) metabolisms were significantly changed in CSF of PLHIV, which might affect the cognitive status of PLHIV via affecting neuron energy support, signaling transduction, and neuroinflammation. Conclusion Metabolic profiles were significantly altered in CSF and might play key roles in the etiology of cognitive impairment of PHLIV. Further explore the exact mechanism for these metabolic changes might be useful for cognitive impairment management of PHLIV., CSF samples from 10 HIV‐infected patients and 10 healthy controls were collected. Then, the metabolic profiles of PLHIV CSFs were analyzed with healthy individual as the normal controls using the untargeted GC/TOFMS. Following this, KEGG annotation and pathway analysis were performed to further explore the underlying mechanism of these metabolic alterations in cognitive impairment of PLHIV.

Studies on the 2019 novel coronavirus disease (COVID-19) have generally been limited to the description of the epidemiology and initial clinical characteristics. We investigated the temporal progression in patients with COVID-19.In this retrospective, single-center study, we included confirmed cases of COVID-19 from Jan 20 to Feb 6, 2020 in Shanghai. Final date of follow-up was February 25, 2020.Of the 249 patients enrolled, the median age was 51 years old, and 126 (50.6%) were male. The duration from onset of symptoms to hospitalization was 4(2-7) days in symptomatic patients. Fever was occurred in 235(94.3%) patients. A total of 215 (86.3%) patients had been discharged after 16(12-20) days hospitalization. The estimated median duration of fever in all the patients with fever was 10 days (95 confidential intervals [CIs]: 8-11 days) after onset of symptoms. Patients who were transferred to intensive care units (ICU) had significantly longer duration of fever as compared to those not in ICU (31 days v.s. 9 days after onset of symptoms, respectively, P 0.0001). Radiological aggravation of initial image was observed in 163 (65.7%) patients on day 7 after onset of symptoms. 154(94.5%) of these patients showed radiological improvement on day 14. The median duration to negative reverse-transcriptase PCR tests of upper respiratory tract samples was 11 days (95 CIs: 10-12 days). Viral clearance was more likely to be delayed in patients in ICU than those not in ICU (P 0.0001). In multivariate logistical analysis, age (Odds ratio [OR] = 1.06) and CD4 T cell count (OR = 0.55 per 100 cells/ul increase) were independently associated with ICU admission.The majority of COVID-19 cases are mild. The clinical progression pattern suggests that early control of viral replication and application of host-directed therapy in later stage is essential to improve the prognosis of CVOID-19.

Because people living with HIV (PLWH) are ageing, they will inevitably develop non-communicable diseases (NCDs) and the number of non-HIV medications will increase. Drug-drug interactions(DDIs) will become an ever-increasing issue. However, little is known about this important issue in Chinese PLWH. This study aimed to investigate the prevalence and risk factors of DDIs among PLWH in China.Chinese PLWH aged ≥18 years were enrolled prospectively from October 2018 to April 2019 and after informed consent was obtained, they were ask to fill out a questionnaire about comorbidity and co-medications. Potential DDIs were identified using the University of Liverpool HIV Drug Interaction Checker.A total of 1804 questionnaires were included. Antiretroviral drugs (ARVs) that most frequently were prescribed were lamivudine (96.18%), efavirenz(64.64%) and tenofovir(60.62%). 16.96% of the participations reported current co-infection with HIV and14.69% reported NCDs. 263(14.57%) participations reported they had used co-medications in the past six months while 186(10.31%) reported they were taking co-medications. Age≥50 years (p 0.001), living in developed areas(p 0.001) and lower CD4 cell count(p = 0.045) were independently associated with the use of co-medications. Potential DDIs were identified in 54 (19.15%) persons using co-medications. Age≥50 [OR = 2.272(1.241-4.158)], PLWH with NCDs[OR = 2.889(1.509-5.532)] and usage of protease inhibitors[OR = 2.538(1.250-5.156)] were independently associated with the potential DDIs.The prevalence of the use of co-medications and potential DDIs among Chinese PLWH are low. Older age, NCDs and use of PIs were risk factors for the potential of developing DDIs. With the aging of PLWH, co-medications and DDIs in China warrants more attention.

Yinzhong Shen, Jingna Xun, Wei Song, Zhenyan Wang, Jiangrong Wang, Li Liu, Renfang Zhang, Tangkai Qi, Yang Tang, Jun Chen, Jianjun Sun, Hongzhou Lu Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, People’s Republic of ChinaCorrespondence: Hongzhou Lu Email luhongzhou@fudan.edu.cnPurpose: Tuberculosis (TB) is the leading cause of mortality in individuals infected with human immunodeficiency virus (HIV), yet the methods for detecting Mycobacterium tuberculosis at an early stage remain insensitive or ineffective. This study aimed to discover plasma biomarkers for distinguishing HIV-TB coinfected individuals from HIV individuals without TB (HIV-nonTB).Patients and Methods: A total of 200 Chinese HIV-positive patients were recruited, 100 each for HIV-nonTB group and HIV-TB group. Plasma proteomic profiles were analyzed for 50 patients each in both groups, using data-independent acquisition (DIA)-mass spectrometry-based proteomics. Differently expressed proteins were revealed with ridge regression analysis. Enzyme-linked immunosorbent assay (ELISA) analyses were performed for further validation in other 100 patients.Results: DIA-mass spectrometry revealed 13 upregulated and 33 downregulated proteins in the HIV-TB group. AMACR (α-methylacyl-CoA racemase), LDHB (L-lactate dehydrogenase B chain), and RAP1B (Ras-related protein Rap-1b) were selected for building a diagnostic model, for which the receiver operation characteristic curve had under areas of 0.99 and 0.89 testing with proteomics data (sensitivity = 92%, specificity = 100%) and ELISA data (sensitivity = 76%, specificity = 92%), respectively.Conclusion: The combination of AMACR, LDHB, and RAP1B proteins may serve as a potential marker of TB in HIV-infected patients.Keywords: diagnosis, coinfection, AIDS-related opportunistic infections, Mycobacterium tuberculosis, ROC curve, proteome

OBJECTIVES The aim was to determine the effectiveness of the serum cryptococcal antigen (CrAg) test in the diagnosis of concurrent cryptococcal meningitis (CM) and as a predictor of mortality in HIV-infected patients. METHODS In this retrospective study, all HIV-infected patients admitted to Shanghai Public Health Clinical Center from 1 January 2014 to 31 August 2016 were screened for serum CrAg using the latex agglutination test. Serum CrAg-positive patients underwent lumbar puncture to confirm CM prior to the initiation of appropriate antifungal therapy and were followed up for at least 6 months. RESULTS One hundred and four (7.1%) of the total of 1474 HIV-infected patients screened were serum CrAg-positive. CM was diagnosed in the majority of serum CrAg-positive patients (71.3%; 67 of 94) and was confirmed in all (46 of 46) of the patients with headache or coma and in 43.8% (21 of 48) of patients without neurological symptoms. CrAg titres ≥ 1:1024 showed a sensitivity of 82.5% and a specificity of 86.7% for the diagnosis of concurrent CM (P

Identification of factors associated with the size of the Human Immunodeficiency Virus reservoir remains a priority for HIV cure research. We report that the activity of Indoleamine 2,3-Dioxygenase, an immunoregulatory enzyme that metabolizes tryptophan to kynurenines, is associated with the size of the HIV reservoir., Background Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that metabolizes tryptophan to immunosuppressive kynurenines. We investigated whether IDO activity is associated with the size of HIV reservoir. Methods Total human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells (PBMCs) from 127 HIV-infected patients receiving antiretroviral therapy (ART) was quantified. Tryptophan and kynurenine concentrations, as well as microbial translocation markers, were measured in plasma samples. T-cell activation and exhaustion in PBMCs were assessed by flow cytometry. Results Elevated IDO activity prior to ART correlated with on-ART HIV DNA (r = 0.35, P = .004), but was not associated with pre-ART HIV DNA. A median duration of 15 months of ART significantly decreased IDO activity; however, these levels were still higher than those observed in HIV-uninfected controls. Among treated participants, IDO activity positively correlated with their concurrent HIV DNA (r = 0.36, P < .0001). Multivariate model showed an independent association of pre-ART CD4/CD8 ratio (adjusted odds ratio [aOR], 0.75 per 0.1 increase [95% confidence interval {CI}, .62–.91]) and on-ART IDO activity (aOR, 1.09 per nM/μM increase [95% CI, 1.04–1.14]) with higher levels of HIV DNA on-ART. A lack of association of the microbial translocation markers was observed with the size of HIV reservoir. HIV DNA positively correlated with the proportions of activated CD4 T and CD8 T cells and exhausted CD4 T cells. Conclusions We observed a positive correlation between IDO activity and total HIV DNA in blood, highlighting the important role of immunometabolic aberrations in HIV persistence.

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.

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

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

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.

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.

Acinetobacter baumannii (AB) infection is an increasing global threaten to hospitalized patients, especially those with impaired immune function. Still, few studies addressed the disease burdens and outcomes of AB infection in HIV patients. We aimed to describe characteristics and outcomes of AB infections in patients with HIV, measure the impact of AB infection on 28-day mortality in HIV patients, as well as assess the predictors of 28-day survival among HIV patients with AB pneumonia. A retrospective study with HIV/AB co-infected patients was conducted at Shanghai Public Health Clinical Center (SPHCC), China. Patients with AB pneumonia were further analyzed for predictors of mortality, as well as an additional 1:1 case-control study to determine the fatality of AB pneumonia compared with pneumonia of other pathogens. We found the incidence of AB infection was 17.4 cases per 100 person-years among all hospitalized HIV patients. Hospital mortality rate was 37.5% (21/56). There was a higher 28-day mortality rate in HIV patients with pneumonia due to AB than other pathogens (34% vs 16%, P = 0.03). APACHE II score was independently associated with 28-day survival by multivariate logistic regression (P = 0.031). Our findings indicate that AB infection is incident and can be fatal in HIV seropositive population. AB infection is an independent risk factor of mortality in patients with HIV and pneumonia. A lower APACHE II score on admission predicts a higher 28-day survival rate among HIV/AB co-infected patients.

The roles of immunodeficiency and combined antiretroviral therapy (cART) in shaping the gut microbiota in HIV-1-infected subjects (HISs) have not been described thoroughly by time-series investigations. In this study, 36 antiretroviral-naïve HISs were enrolled to prospectively assess alterations in the fecal microbiota and plasma markers of microbial translocation and inflammation with cART. At baseline, the species α-diversity of the fecal microbiota was significantly lower in HISs with a CD4+ T cell count 300/mm3 (Shannon index: Median 2.557 vs. 2.981, P = 0.006; Simpson index: Median 0.168 vs. 0.096, P = 0.004). Additionally, the baseline α-diversity indices correlated with CD4+ T cell counts (Shannon index: r = 0.474, P = 0.004; Simpson index: r = −0.467, P = 0.004) and the specific plasma biomarkers for microbial translocation and inflammation. After cART introduction, the species α-diversity of fecal microbiota in HISs with CD4+ T cell counts 300/mm3 (Shannon index: Median 2.981 vs. 2.934, P = 0.179; Simpson index: Median 0.096 vs. 0.119, P = 0.082). Meanwhile, with cART introduction, alterations in the gut microbial composition were more significant in the subgroup with CD4+ T cell counts >300/mm3, corresponding to increases in the specific plasma inflammatory markers. These findings implicated the interactive roles of immunodeficiency and cART for affecting gut microbiota in HIV-1-infected individuals, providing new insights into intestinal microbiome dysbiosis related to HIV-1 infection.

OBJECTIVES Human immunodeficiency virus positive (HIV+) individuals report hearing difficulties, but standard audiological tests show no, or small, changes in peripheral hearing ability. The hearing complaints may reflect central nervous system (CNS) auditory processing deficits, rather than middle or inner ear problems, and may result from CNS damage due to HIV infection or treatment. If central auditory task performance and cognitive deficits in HIV+ individuals are shown to be related, then central auditory tests might serve as a "window" into CNS function in these patients. DESIGN We measured cognitive performance (Mandarin Montreal Cognitive Assessment [MoCA]) and speech in noise perception (Mandarin hearing-in-noise test [HINT]) in 166 normal-hearing HIV+ individuals (158 men, 8 women, average age 36 years) at the Shanghai Public Health Clinical Center in Shanghai, China. Data collection included audiometry, tympanometry, and the Amsterdam Inventory of Auditory Handicap (AIAH), which assesses the subjective ability to understand speech and localize sound. RESULTS Subjects had no middle ear disease and met criteria for normal-hearing sensitivity (all thresholds 20 dB HL or less). A significant negative relationship between speech reception thresholds (SRT) and MoCA scores (r = 0.15, F = 28.2, p < 0.001) existed. Stepwise linear regression showed that when the factors of age, MoCA scores, hearing thresholds, and education level were considered, only age and MoCA scores contributed independently to the SRT results (overall model r = 0.30, F = 38.8, p < 0.001). Subjective hearing complaints from the AIAH supported the HINT results. AIAH and MoCA scores were also related (r = 0.05, F = 8.5, p = 0.004), with those with worse MoCA scores having more problems on the AIAH. When the cohort was divided into those with normal and abnormal performance on the MoCA, those with abnormal performance on the MoCA had significantly higher average SRTs (p < 0.001). CONCLUSIONS Understanding speech in noise measured both objectively with the HINT and subjectively with the AIAH was inversely related to cognitive abilities despite a normal ability to hear soft sounds determined by audiometry. Although age was also an important independent factor affecting speech perception, the age relationship within the speech findings in this study may represent more than just age-related declines in speech in noise understanding. Although reliable data on disease duration are not available, the older members of this cohort likely had HIV longer and probably had more severe symptoms at presentation than the younger members because early detection and treatment of HIV in Shanghai has improved over time. Therefore, the age relationship may also include elements of disease duration and severity. Speech perception, especially in challenging listening conditions, involves cortical and subcortical centers and is a demanding neurological task. The problems interpreting speech in noise HIV+ individuals have may reflect HIV-related or HIV treatment-related, central nervous damage, suggesting that CNS complications in HIV+ individuals could potentially be diagnosed and monitored using central auditory tests.

Background Tuberculosis infection still places a great burden on HIV-infected individuals in China and other developing countries. Knowledge of the survival of HIV-infected patients with pulmonary tuberculosis (PTB) would provide important insights for the clinical management of this population, which remains to be well described in current China. Methods HIV-infected patients with PTB admitted to Shanghai Public Health Clinical Center from January 2011 to December 2015 were retrospectively enrolled. In this cohort, the survival prognosis was estimated by the Kaplan-Meier method, while univariate and multivariate Cox proportional hazards models were used to determine the risk factors affecting mortality. Results After reviewing 4914 admitted patients with HIV infection, 359 PTB cases were identified. At the time of PTB diagnosis, the patients’ median CD4+ T cell count was 51 /mm3 (IQR: 23–116), and 27.30% of patients (98/359) were on combination antiretroviral therapy (cART). For the 333 cases included in the survival analysis, the overall mortality was 15.92% (53/333) during a median 27-month follow-up. The risk factors, including age older than 60 years (HR: 3.18; 95% CI: 1.66–6.10), complication with bacterial pneumonia (HR: 2.64; 95% CI: 1.30–5.35), diagnosis delay (HR: 2.60; 95% CI: 1.42–4.78), CD4+ T cell count less than 50/mm3 (HR: 2.38; 95% CI: 1.27–4.43) and pulmonary atelectasis (HR: 2.20; 95% CI: 1.05–4.60), might independently contribute to poor survival. Among patients without cART before anti-TB treatment, the later initiation of cART (more than 8 weeks after starting anti-TB treatment) was found to increase the mortality rate (OR: 4.33; 95% CI: 1.22–15.36), while the initiation of cART within 4–8 weeks after starting anti-TB treatment was associated with the fewest deaths (0/14). Conclusions The subjects in this study conducted in the cART era were still characterized by depressed immunological competence and low rates of cART administration, revealing possible intervention targets for preventing TB reactivation in HIV-infected individuals under current circumstances. Furthermore, our study indicated that the timely diagnosis of PTB, prevention of secondary bacterial pneumonia by prophylactic management and optimization of the timing of cART initiation could have significant impacts on decreasing mortality among HIV/PTB co-infected populations. These findings deserve further prospective investigations to optimize the management of HIV/PTB-co-infected patients. Trial registration NCT01344148, Registered September 14, 2010. Electronic supplementary material The online version of this article (10.1186/s40249-018-0405-8) contains supplementary material, which is available to authorized users.

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