Serum globulin levels are associated with HIV reservoir size and immune restoration during long-term ART.

OBJECTIVES: The objectives of this study were to analyze the relationship between serum globulin levels and immune restoration and HIV reservoir size during long-term antiretroviral therapy (ART). METHODS: We enrolled 13 patients living with HIV who had been receiving ART for 5 years. We measured levels of serum globulin, cell-associated (CA) HIV DNA and RNA, and p24 antibody at 0, 1, 3, and 5 years of ART. CD38 and human leukocyte antigen - DR isotype (HLA-DR) were used as activation markers for T-cell activation. Serum concentrations of the inflammatory cytokines interferon gamma-inducible protein (IP)-10 and soluble CD163 (sCD163) were detected by enzyme-linked immunosorbent assay. We analyzed the relationship between serum globulin levels, HIV reservoir size, immune restoration, T-cell immune activation, and inflammatory levels during long-term ART. RESULTS: Our data showed that serum globulin levels in people living with HIV were higher than in healthy controls and significantly decreased during the first year of ART. Serum globulin levels during long-term ART were positively correlated with CA HIV DNA, CA HIV RNA, p24 antibody levels, and CD8+ T-cell counts and negatively correlated with CD4+ T-cell counts and CD4/CD8 ratios. Moreover, serum globulin levels were positively correlated with CD4+ and CD8+ T-cell activation and the concentrations of inflammatory biomarkers IP-10 and sCD163 during long-term ART. CONCLUSIONS: Our findings suggest that serum globulin levels may be associated with HIV reservoir size and immune restoration during long-term ART.

Genetic characteristics of a novel HIV-1 recombinant lineage (CRF103_01B) and its prevalence in northern China.

During the routine surveillance of HIV-1 pretreatment drug resistance in Beijing, five men who have sex with men (MSM) and a woman were observed to get infected by newly identified CRF103_01B strain. To elucidate the genetic characteristics, the near full-length genome (NFLG) was obtained. Phylogenetic inference indicated that CRF103_01B NFLG was composed of six mosaic segments. Segments IV and V of CRF103_01B were located among the clusters subtype B and CRF01_AE (group 5), respectively. The CRF103_01B strain was deduced to originate from Beijing MSM population around 2002.3-2006.4 and continued to spread among MSM population at a low level, then to the general population via heterosexual contact in northern China. Molecular epidemiology surveillance of CRF103_01B should be reinforced.

Incidence and risk factors of hypertriglyceridemia in males with human immunodeficiency virus who are treated with combination antiretroviral therapy: a retrospective cohort study.

BACKGROUND: Hypertriglyceridemia is associated with subclinical atherosclerosis and vascular inflammation even when low-density lipoprotein cholesterol levels are normal. However, few cohort studies on hypertriglyceridemia have been conducted in males with higher susceptibility to human immunodeficiency virus (HIV)-related deterioration of arterial structure and function. Our objective was to investigate the incidence of hypertriglyceridemia during treatment with combination antiretroviral therapy (cART) in males with HIV and explore its related risk factors. METHODS: In this retrospective study, we included 309 males living with HIV (median age 31 years [interquartile range 26-42.5]) who initiated cART treatment in our hospital from January 2013 to December 2018. We collected follow-up data on serum triglycerides and other related information as of June 31, 2021. A Cox proportional hazards regression model was used to analyze the related risk factors. RESULTS: In 666.7 person-years, hypertriglyceridemia occurred in 140 patients (triglyceride ≥2.3 mmol/L [200 mg/dL]), and the incidence rate was 21.0 per 100 person-years (Patients who took the lamivudine [3TC] + tenofovir disoproxil fumarate [TDF] + efavirenz [EFV] regimen accounted for 77.0% of the total patients.). Multiple Cox regression analysis showed that baseline CD4/CD8 ratio < 0.20 (hazard ratio [HR], 2.705 [95% confidence interval (CI): 1.381-5.296]; P = 0.004}, body mass index (BMI) ≥ 24.0 kg/m2 (HR, 1.768 [95% CI: 1.225-2.552]; P = 0.002), borderline high triglyceride at baseline (HR, 3.457 [95% CI: 2.162-5.527]; P < 0.001), and 3TC + zidovudine (AZT) + EFV regimen (HR, 2.702 [95% CI: 1.593-4.581]; P < 0.001), or 3TC + TDF + lopinavir/ritonavir (LPV/r) regimen (HR, 4.349 [95% CI: 2.664-7.102]; P < 0.001) were independent risk factors for hypertriglyceridemia. CONCLUSION: During the course of cART treatment, the incidence of hypertriglyceridemia in males with HIV was high. The main risk factors influencing its occurrence are a low baseline CD4/CD8 ratio, overweight and obesity, and the use of AZT or LPV/r in the cART regimen.

Compromised long-lived memory CD8+ T cells are associated with reduced IL-7 responsiveness in HIV-infected immunological nonresponders.

Immune deficiency is one of the hallmarks of HIV infection and a major cause of adverse outcomes in people living with HIV (PLWH). Long-lived memory CD8+ T cells (LLMCs) are essential executors of long-term protective immunity; however, the generation and maintenance of LLMCs during chronic HIV infection are not well understood. In the present study, we analyzed circulating LLMCs in healthy controls (HCs) and PLWH with different disease statuses, including treatment naïve patients (TNs), complete responders (CRs), and immunological nonresponders (INRs). We found that both TNs and INRs showed severely compromised LLMCs compared with HCs and CRs, respectively. The decrease of LLMCs in TNs correlated positively with the reduction of their precursors, namely memory precursor effector T cells (MPECs), which might be associated with elevated pro-inflammatory cytokines. Strikingly, INRs showed an accumulation of MPECs, which exhibited diminished responsiveness to interleukin 7 (IL-7), thereby indicating abrogated differentiation into LLMCs. Moreover, in vitro studies showed that treatment with dexamethasone could improve the IL7-phosphorylated (p)-signal transducer and activator of transcription (STAT5) response by upregulating the expression of the interleukin 7 receptor (IL-7Rα) on MPECs in INRs. These findings provide insights that will encourage the development of novel therapeutics to improve immune function in PLWH.

Incidence of and risk factors for liver damage in patients with HIV-1 mono-infection receiving antiretroviral therapy.

OBJECTIVES: The study aimed to investigate the incidence of and risk factors for liver damage in patients with human immunodeficiency virus type-1 (HIV-1) mono-infection receiving antiretroviral therapy (ART). METHODS: We retrospectively analyzed the clinical data of patients who were diagnosed with HIV-1 infection and initiated ART from January to December 2017. Among them, 382 patients with HIV-1 mono-infection and normal baseline liver function were included in the analysis. The incidence of liver damage at each follow-up point, and possible risk factors for liver damage were evaluated via COX regression survival analyses. RESULTS: The overall incidence of liver damage (grade I-IV) was 27.23% (interquartile range [IQR]: 26.38%-28.72%). Grade I liver damage was most common and accounted for 22.13% of cases (IQR: 21.06%-24.04%), while grade II liver damage accounted for 3.40% of cases (IQR: 3.19%-4.26%). COX regression and survival analyses revealed that baseline body mass index (BMI), alanine aminotransferase (ALT) level, CD4+ T cell count, HIV-1 viral load, and the antiretroviral regimen were significantly correlated with the occurrence of liver damage. Moreover, baseline ALT levels and HIV-1 viral load were identified as independent risk factors for liver damage in patients with HIV-1 mono-infection. CONCLUSION: Liver damage is common in patients with HIV-1 mono-infection undergoing ART. Patients with risk factors for liver damage should be well-informed before the initiation of ART, and liver function should be closely monitored during ART even in patients with normal liver function before ART.

Dynamics of HIV reservoir decay and naïve CD4 T-cell recovery between immune non-responders and complete responders on long-term antiretroviral treatment.

BACKGROUND: The dynamics of viral reservoir decay and naïve CD4 T-cell recovery between immunological non-responders (INR) and complete responders (CR) during long-term antiretroviral treatment (ART) are not fully known. METHODS: Twenty-eight chronic HIV-infected individuals on 5-year ART were divided into two groups: INR (CD4 counts ≤350 cells/µL, n = 13) and CR (CD4 counts ≥500 cells/µL, n = 15). The levels of HIV DNA and cell-associated HIV RNA (CA-RNA), CD4 counts, naïve CD4 counts and their correlations were analyzed at baseline, years 1, 3 and 5 of ART between the two groups. Expression of PD-1 on CD4 T-cells was quantified by flow cytometry. Linear mixed effect models were used to estimate the change procession in repeated measurements over 5 years. Slopes of the above-mentioned indicators were estimated using participant-specific linear regressions, respectively. RESULTS: INR maintained higher levels of HIV DNA and CA-RNA with higher percentages of PD-1+CD4 T-cells compared with CR during 5-year ART, concurrent with lower naïve CD4 T-cells. However, the rates of HIV DNA and CA-RNA decay in INR were not different from that in CR over time, and INR had higher rates of naïve CD4 T-cell percentage recovery. The baseline levels of HIV DNA were positively associated with the 5-year levels of HIV DNA, but negatively associated with the 5-year naïve CD4 counts. CONCLUSIONS: INR maintained significantly higher viral reservoir and lower naïve CD4 T-cells compared with CR during 5-year ART, however, the rates of reservoir decay and naïve CD4 T-cell percentage growth within INR were not lower than that in CR over time.

Transforming growth factor-ß promotes the function of HIV-specific CXCR5+ CD8 T cells.

HIV replication can be inhibited by CXCR5+ CD8 T cells (follicular cytotoxic T cell [TFC]) which transfer into B-cell follicles where latent HIV infection persists. However, how cytokines affect TFC remain unclear. Understanding which cytokines show the ability to affect TFC could be a key strategy toward curing HIV. Similar mechanisms could be used for the growth and transfer of TFCs and follicular helper T (TFH) cells; as a result, we hypothesized that cytokines IL-6, IL-21, and transforming growth factor-ß (TGF-ß), which are necessary for the differentiation of TFH cells, could also dictate the development of TFCs. In this work, lymph node mononuclear cells and peripheral blood mononuclear cells from HIV-infected individuals were cocultured with IL-6, IL-21, and TGF-ß. We then carried out T-cell receptor (TCR) repertoire analysis to compare the differences between CXCR5- and CXCR5+ CD8 T cells. Our results showed that the percentage and function of TFC can be enhanced by stimulation with TGF-ß. Besides, TGF-ß stimulation enhanced the diversity of TCR and complementarity-determining region 3 sequences. HIV DNA showed a negative correlation with TFC. The use of TGF-ß to promote the expression of CXCR5+ CD8 T cells could become a new treatment approach for curing HIV.

Higher viral load and genetic diversity of HIV-1 in seminal compartments than in blood of seven Chinese men who have sex with men and have early HIV-1 infection.

To date, there have been no reports characterizing HIV-1 in the semen of Chinese men who have sex with men (MSM) with early infection. In this study, genetic diversity and viral load of HIV-1 in the seminal compartments and blood of Chinese MSM with early HIV-1 infection were examined. Viral load and genetic diversity of HIV-1 in paired samples of semen and blood were analyzed in seven MSM with early HIV-1 infection. HIV-1 RNA and DNA were quantitated by real-time PCR assays. Through sequencing the C2-V5 region of the HIV-1 env gene, the HIV-1 genotype and genetic diversity based on V3 loop amino acid sequences were determined by using Geno2pheno and PSSM programs co-receptor usage. It was found that there was more HIV-1 RNA in seminal plasma than in blood plasma and total, and more 2-LTR circular and integrated HIV-1 DNA in seminal cells than in peripheral blood mononuclear cells from all seven patients with early HIV-infection. There was also greater HIV-1 genetic diversity in seminal than in blood compartments. HIV-1 in plasma displayed higher genetic diversity than in cells from the blood and semen. In addition, V3 loop central motifs, which present some key neutralizing antibody epitopes, varied between blood and semen. Thus, virological characteristics in semen may be more representative when evaluating risk of transmission in persons with early HIV infection.

Retrospective Study on Genetic Diversity and Drug Resistance among People Living with HIV at an AIDS Clinic in Beijing.

(1) Background: The objective of this study was to investigate the prevalence of genetic diversity and drug resistance mutations among people living with HIV (PLWH) attending clinics in Beijing. (2) Methods: A retrospective analysis was conducted on PLWH admitted to the Fifth Medical Center of People's Liberation Army (PLA) General Hospital between 1 March 2013 and 31 July 2020. The participants were analyzed for pretreatment drug resistance (PDR) and acquired drug resistance (ADR). Nested polymerase chain reaction (PCR) was utilized to amplify the pol gene from plasma RNA samples obtained from the participants. Genotypic and HIV drug resistance were determined using the Stanford University HIV Drug Resistance Database. Univariate and multifactorial logistic analyses were used to assess the risk factors for PDR. (3) Results: The overall prevalence rates of PDR and ADR were 12.9% and 27.8%, respectively. Individuals treated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) exhibited the highest prevalence of mutations. Specific mutation sites, such as V179D for NNRTIs and M184V and K65R for nucleoside reverse transcriptase inhibitors (NRTIs), were identified as prevalent mutations. Individuals treated with efavirenz (EFV) and nevirapine (NVP) were found to be susceptible to developing resistance. The multifactorial regression analyses indicated that the factors of circulating recombination form (CRF) genotype CRF07-BC and a high viral load were associated with an increased risk of PDR. CRF01-AE and CRF07-BC were the most prevalent HIV genotypes in our study. (4) Conclusions: The distribution of HIV genotypes in Beijing is complex. There is a need for baseline screening for HIV drug resistance among ART-naive individuals, as well as timely testing for drug resistance among ART-experienced individuals.

Landscape of gut mucosal immune cells showed gap of follicular or memory B cells into plasma cells in immunological non-responders.

BACKGROUND: The gut is an important site for human immunodeficiency virus (HIV) infection and immune responses. The role of gut mucosal immune cells in immune restoration in patients infected with HIV undergoing antiretroviral therapy remains unclear. METHODS: Ileocytes, including 54 475 immune cells, were obtained from colonoscopic biopsies of five HIV-negative controls, nine immunological responders (IRs), and three immunological non-responders (INRs) and were analyzed using single-cell RNA sequencing. Immunohistochemical assays were performed for validation. The 16S rRNA gene was amplified using PCR in faecal samples to analyze faecal microbiota. Flow cytometry was used to analyze CD4+ T-cell counts and the activation of T cells. RESULTS: This study presents a global transcriptomic profile of the gut mucosal immune cells in patients infected with HIV. Compared with the IRs, the INRs exhibited a lower proportion of gut plasma cells, especially the IGKC+IgA+ plasma cell subpopulation. IGKC+IgA+ plasma cells were negatively associated with enriched f. Prevotellaceae the INRs and negatively correlated with the overactivation of T cells, but they were positively correlated with CD4+ T-cell counts. The INRs exhibited a higher proportion of B cells than the IRs. Follicular and memory B cells were significantly higher in the INRs. Reduced potential was observed in the differentiation of follicular or memory B cells into gut plasma cells in INRs. In addition, the receptor-ligand pairs CD74_MIF and CD74_COPA of memory B/ follicular helper T cells were significantly reduced in the INRs, which may hinder the differentiation of memory and follicular B cells into plasma cells. CONCLUSIONS: Our study shows that plasma cells are dysregulated in INRs and provides an extensive resource for deciphering the immune pathogenesis of HIV in INRs. KEY POINTS: An investigation was carried out at the single-cell-level to analyze gut mucosal immune cells alterations in PLWH after ART. B cells were significantly increased and plasma cells were significantly decreased in the INRs compared to the IRs and NCs. There are gaps in the transition from gut follicular or memory B cellsinto plasma cells in INRs.

HLA-mismatched allogeneic adoptive immune therapy in patients with severely immunosuppressed AIDS: a multicenter, open-label, controlled, phase 2a study.

Recurrent opportunistic infections (OIs) in patients with severely immunosuppressed AIDS remain an unresolved medical challenge despite advancements in antiretroviral therapy (ART). To address this gap, we developed an HLA-mismatched allogeneic adoptive immune therapy (AAIT) specifically targeting this patient population. The safety and efficacy of this novel therapeutic approach were preliminarily confirmed in our phase 1 trial. Subsequently, a multicenter, open-label, controlled, phase 2a trial was conducted to evaluate the efficacy of AAIT in combination with ART compared with the conventional ART-only regimen. No difference in the incidence of adverse events (AEs) was observed between the two groups at the 96-week follow-up. AAIT treatment improved CD4+ T cell recovery at weeks 72 (P = 0.048) and 96 (P = 0.024) compared to the Control Group. Additionally, stratified analysis of patients in the AAIT Group showed that donor/recipient sex mismatch was significantly associated with the likelihood of patients achieving an immunological response (OR = 8.667; 95% CI, 2.010-37.377; P = 0.004). These findings suggest that AAIT serves as a promising adjunct therapy for improving the outcomes of patients with severely immunosuppressed AIDS. Further studies are needed to elucidate the immunological mechanisms underlying AAIT and identify the subpopulations that respond optimally to this therapeutic approach. This trial is registered at www.clinicaltrials.gov (NCT04098770).Trial registration: ClinicalTrials.gov identifier: NCT04098770.Trial registration: ClinicalTrials.gov identifier: NCT02651376.

Genetic Characteristics of Two Unique Recombinant Forms of HIV-1 CRF01_AE/CRF07_BC by Near Full-Length Genome from Men Who Have Sex with Men in Beijing, China.

Two HIV-1 infections with unassigned genotypes were identified during HIV-1 pretreatment drug resistance surveillance. The near full-length genome sequences of BL5040-00 and BL5085-00 were obtained and were classified as unique recombinant forms (URFs) between CRF01_AE and CRF07_BC. Simplot (version 3.5) analyses showed that the two URFs shared similar recombinant forms, and in the backbone belonging to CRF01_AE, the gag-pol, vpu, env, and nef gene fragments were genetically substituted by CRF07_BC. BL5040-00, with 10 breakpoints, had 6 CRF07_BC fragments and 5 CRF01_AE fragments, whereas BL5085-00, with 6 breakpoints, had 4 CRF07_BC fragments and 3 CRF01_AE fragments. BL5040-00 strain had two additional recombination breakpoints in pol-vif gene. The presence of URFs suggests that the men who have sex with men population in Beijing has an active HIV epidemic and the genetic diversity of HIV-1 is complex, emphasizing molecular epidemiology and disease progression monitoring should be strengthened.

COVID-19 vaccination in people living with HIV and AIDS (PLWHA) in China: A cross-sectional study.

COVID-19 appears to put people living with HIV and AIDS (PLWHA) at a higher risk of catastrophic consequences and mortality. However, investigations on the hesitancy and vaccination behavior of PLWHA in China were lacking compared to the general population. From January 2022 to March 2022, we conducted a multi-center cross-sectional survey of PLWHA in China. Logistic regression models were used to examine factors associated to vaccine hesitancy and COVID-19 vaccine uptake. Among 1424 participants, 108 participants (7.6%) were hesitant to be vaccinated while 1258 (88.3%) had already received at least one dose of the COVID-19 vaccine. Higher COVID-19 vaccine hesitancy was associated with older age, a lower academic level, chronic disease, lower CD4+ T cell counts, severe anxiety and despair, and high perception of illness. Lower education level, lower CD4+ T cell counts, and significant anxiety and depression were all associated with a lower vaccination rate. When compared to vaccinated participants, those who were not hesitant but nevertheless unvaccinated had a higher presence of chronic disease and lower CD4+ T cell count. Tailored interventions (e.g. targeted education programs) based on these linked characteristics were required to alleviate concerns for PLWHA in promoting COVID-19 vaccination rates, particularly for PLWHA with lower education levels, lower CD4+ T cell counts, and severe anxiety and depression.

Abnormal blood microbiota profiles are associated with inflammation and immune restoration in HIV/AIDS individuals.

IMPORTANCE: The characteristics of blood microbiota in HIV-infected individuals and their relevance to disease progression are still unknown, despite alterations in gut microbiota diversity and composition in HIV-infected individuals. Here, we present evidence of increased blood microbiota diversity in HIV-infected individuals, which may result from gut microbiota translocation. Also, we identify a group of microbes, Porphyromonas gingivalis, Prevotella sp. CAG:5226, Eubacterium sp. CAG:251, Phascolarctobacterium succinatutens, Anaerobutyricum hallii, Prevotella sp. AM34-19LB, and Phocaeicola plebeius, which are linked to poor immunological recovery. This work provides a scientific foundation toward therapeutic strategies targeting blood microbiota for immune recovery of HIV infection.

Distinct inflammation-related proteins associated with T cell immune recovery during chronic HIV-1 infection.

Chronic inflammation and T cell dysregulation persist in individuals infected with human immunodeficiency virus type 1 (HIV-1), even after successful antiretroviral treatment. The mechanism involved is not fully understood. Here, we used Olink proteomics to comprehensively analyze the aberrant inflammation-related proteins (IRPs) in chronic HIV-1-infected individuals, including in 24 treatment-naïve individuals, 33 immunological responders, and 38 immunological non-responders. T cell dysfunction was evaluated as T cell exhaustion, activation, and differentiation using flow cytometry. We identified a cluster of IRPs (cluster 7), including CXCL11, CXCL9, TNF, CXCL10, and IL18, which was closely associated with T cell dysregulation during chronic HIV-1 infection. Interestingly, IRPs in cluster 5, including ST1A1, CASP8, SIRT2, AXIN1, STAMBP, CD40, and IL7, were negatively correlated with the HIV-1 reservoir size. We also identified a combination of CDCP1, CXCL11, CST5, SLAMF1, TRANCE, and CD5, which may be useful for distinguishing immunological responders and immunological non-responders. In conclusion, the distinct inflammatory milieu is closely associated with immune restoration of T cells, and our results provide insight into immune dysregulation during chronic HIV-1 infection.

Effect of SARS-CoV-2 Breakthrough Infection on HIV Reservoirs and T-Cell Immune Recovery in 3-Dose Vaccinated People Living with HIV.

People living with human immunodeficiency virus (PLWH) are a vulnerable population with a higher risk of severe coronavirus disease 2019 (COVID-19); therefore, vaccination is recommended as a priority. Data on viral reservoirs and immunologic outcomes for PLWH breakthrough infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are currently limited. In this study, we investigated the effects of SARS-CoV-2 breakthrough infection on hematological parameters, human immunodeficiency virus (HIV) reservoir size, and T-cell recovery in PLWH receiving antiretroviral therapy (ART) after SARS-CoV-2 booster vaccination. The results indicated that during breakthrough infection, booster vaccination with homologous and heterologous vaccines was safe in PLWH after receiving two doses of inactivated vaccination. The absolute CD4 counts decreased in the heterologous group, whereas the CD8 counts decreased in the homologous booster group after breakthrough infection in PLWH. Breakthrough infection increased HIV reservoirs and was associated with increased T-cell activation in PLWH who received virally suppressed ART and a 3-dose vaccination. According to our data, the breakthrough infection of SARS-CoV-2 may put PLWH at a greater risk for increased HIV reservoirs, even if these individuals were virally suppressed with ART after 3-dose SARS-CoV-2 vaccination.

Elevated glutamate impedes anti-HIV-1 CD8 + T cell responses in HIV-1-infected individuals on antiretroviral therapy.

CD8 + T cells are essential for long-lasting HIV-1 control and have been harnessed to develop therapeutic and preventive approaches for people living with HIV-1 (PLWH). HIV-1 infection induces marked metabolic alterations. However, it is unclear whether these changes affect the anti-HIV function of CD8 + T cells. Here, we show that PLWH exhibit higher levels of plasma glutamate than healthy controls. In PLWH, glutamate levels positively correlate with HIV-1 reservoir and negatively correlate with the anti-HIV function of CD8 + T cells. Single-cell metabolic modeling reveals glutamate metabolism is surprisingly robust in virtual memory CD8 + T cells (TVM). We further confirmed that glutamate inhibits TVM cells function via the mTORC1 pathway in vitro. Our findings reveal an association between metabolic plasticity and CD8 + T cell-mediated HIV control, suggesting that glutamate metabolism can be exploited as a therapeutic target for the reversion of anti-HIV CD8 + T cell function in PLWH.

Optoelectronic Modulation of Silver Antimony Sulfide Thin Films for Photodetection.

Silver antimony sulfide, as a ternary chalcogenide, has attracted great attention in the field of optoelectronics in recent years. In particular, it has appealing properties, such as excellent stability, solution processability, and versatile composition tunability. Benefiting from the recent development of processing techniques, AgSbS2 has emerged as a promising candidate for next-generation, thin-film photovoltaics. On the contrary, AgSbS2-based photodetectors have been barely reported. In this work, we systematically investigated the composition engineering of silver antimony sulfide compounds with a precursor route. Their optoelectronic properties were fully characterized, and the composition was optimized for photodetection. High-performance phototransistors were first reported based on field-effect thin film transistors with interfacial modification. The obtained AgSbS2 phototransistors exhibited relatively high photosensitivity, low dark current and noise, superior device stability, and excellent detectivity covering the whole range from ultraviolet to near-infrared, highlighting the great potential for next-generation photodetection.

Interfacial Engineering of High-Performance, Solution-Processed Sb2S3 Phototransistors.

Antimony sulfide, as a binary chalcogenide, has attracted great attention in the field of optoelectronics in recent years, particularly in photovoltaics, because of its striking merits such as earth elements abundance, excellent stability, chemical versatility, and solution processability. With the rapid development of fabrication techniques and device engineering, the device performance of Sb2S3 solar cells has experienced an unprecedented success. However, photodetectors based on Sb2S3 were barely reported, especially based on the transistor configuration. In this work, we prepared high quality Sb2S3 thin films via a sol-gel method, and Sb2S3 thin films were deposited on zinc-tin oxide based field-effect transistors. Furthermore, an additional electron transport layer was inserted between the Sb2S3 layers and the zinc-tin oxide channels and archived high-performance phototransistors with proper interfacial engineering. The optimized devices exhibited extremely high photosensitivity (106), low dark current (∼10 pA) and noise (∼11 fA Hz-1/2), high detectivity (1 × 1013 Jones), and superior device stability, indicating great potential for next generation solution-processed photodetectors.

Epidemiological trends of severely immunosuppressed people living with HIV at time of starting antiretroviral treatment in China during 2005-2018.

OBJECTIVES: High HIV-related mortality is mainly associated with severe immunosuppression (CD4 count < 50 cells/µL) in people living with HIV (PLWH). This study intended to explore the trends in epidemic and early mortality among PLWH with severe immunosuppression for further targeted intervention. METHODS: We extracted the data of treatment-naïve PLWH with severe immunosuppression from China's National Free Antiretroviral Treatment (ART) Program database. Early mortality (within 6 or 12 months after initiating ART) and spatial, temporal, and population distribution were analyzed during 2005-2018. RESULTS: Of 748,066 treatment-naïve PLWH, 105,785 (14.1%) were severely immunosuppressed PLWH aged more than 15-year-old. The proportion of severely immunosuppressed PLWH peaked at 31.4% and then decreased with time, leveling off at approximately 11-12% from 2015 onward. Early mortality rates of these PLWH declined significantly (from 17.0% to 8.1% after 6 months of initiating ART; 20.4% to 10.6% after 12 months; both p values < 0.01) from 2005-2007 to 2016-2018. In the South-central and Southwest, the number of these PLWH was larger than that in the other regions during 2005-2018, and it increased to 4780 (37.1%) and 3370 (26.2%) in 2018. The proportion of PLWH aged 30-44 years among all treatment-naïve severely immunosuppressed PLWH in each region was higher than that of other age groups during 2005-2018. After the proportion decreased during 2005-2007, the proportion of PLWH aged 45-59 years in Southwest and South-central were increased steadily from 11% (69/626) and 16.7% (358/2140) in 2007 to 33.8% (1138/3370) and 34.0% (1626/4780) in 2018, respectively; the proportion of PLWH aged ≥60 years showed an increasing trend during 2005-2018; while changes in the proportion of those age groups were less pronounced in North and Northeast. The proportion of PLWH infected by heterosexual contact was high at 83% (2798/3370) in Southwest, and 75.1% (3588/4780) in South-central in 2018; conversely, proportion of PLWH infected by homosexual contacts was largest in North (57.8% [500/865]) and Northeast (59.9% [561/936]). CONCLUSIONS: The persistent burden of treatment-naïve PLWH with severe immunosuppression remains challenging. Our results provide evidence for policy-makers to allocate resources and establish targeting strategies to identify early infection of PLWH.