Transcriptomic crosstalk between viral and host factors drives aberrant homeostasis of T-cell proliferation and cell death in HIV-infected immunological non-responders.

BACKGROUND: Immunological non-responders (INRs) among people living with HIV have inherently higher mortality and morbidity rates. The underlying immunological mechanisms whereby failure of immune reconstitution occurs in INRs require elucidation. METHOD: HIV-1 DNA and HIV-1 cell-associated RNA (CA-HIV RNA) quantifications were conducted via RT-qPCR. Transcriptome sequencing (RNA-seq), bioinformatics, and biological verifications were performed to discern the crosstalk between host and viral factors. Flow cytometry was employed to analyze cellular activation, proliferation, and death. RESULTS: HIV-1 DNA and CA-HIV RNA levels were observed to be significantly higher in INRs compared to immunological responders (IRs). Evaluation of CD4/CD8 ratios showed a significantly negative correlation with HIV-1 DNA in IRs, but not in INRs. Bioinformatics analyses and biological verifications showed IRF7/INF-α regulated antiviral response was intensified in INRs. PBMCs of INRs expressed significantly more HIV integrase-mRNA (p31) than IRs. Resting (CD4+CD69- T-cells) and activated (CD4+CD69+ T-cells) HIV-1 reservoir harboring cells were significantly higher in INRs, with the co-occurrence of significantly higher cellular proliferation and cell death in CD4+ T-cells of INRs. CONCLUSION: In INRs, the systematic crosstalk between the HIV-1 reservoir and host cells tends to maintain a persistent antiviral response-associated inflammatory environment, which drives aberrant cellular activation, proliferation, and death of CD4+ T-cells.

Independent predictors of family resilience in patients with ischemic stroke: A cross-sectional survey.

Background: Globally, China bears the highest stroke burden, emphasizing the paramount importance of comprehending the influencing factors on family resilience among patients with ischemic stroke to promote their physical and mental well-being, as well as enhance the quality of their life. This understanding can concurrently assist healthcare professionals in formulating interventions aimed at fostering healthy family functioning. Objective: To investigate the level of family resilience in patients with ischemic stroke and its predictive factors. Methods: A total of 310 inpatients with ischemic stroke were recruited from three tertiary general hospitals in China between May and November 2021. The study employed a range of instruments for data collection, including the General data questionnaire, Family Resilience Rating Scale, Simplified Coping Style Questionnaire, Perceived Social Support Scale and Connor-Davidsion Re-silience Scale. Data analysis was conducted using SPSS 22.0 statistical software. Non-parametric tests, Spearman analysis, and multiple stepwise regression were employed to investigate the predictive variables of family resilience. Results: A total of 303 patients successfully completed the investigation, yielding an efficacy rate of 97.74 %. The total scores for family resilience spanned from 87 to 245, with a median (P25, P75) of 187 (160, 200). The highest scores were observed in the dimension of dilemma interpretation, while the lowest scores were recorded in the dimension of social support. Family relationship (ß = 0.459, P<0.001), positive coping (ß = 0.182, P<0.001), out-of-family support(ß = 0.156, P<0.001), in-family support (ß = 0.147, P = 0.002), and optimism (ß = 0.108, P = 0.013) were found to be predictive factors of family resilience. Conclusion: Patients with high family resilience demonstrated superior family relationship, effective positive coping strategies, increased support within and outside the family, and a more optimistic attitude; these factors independently predict family resilience.

Voriconazole plus flucytosine is not superior to amphotericin B deoxycholate plus flucytosine as an induction regimen for cryptococcal meningitis treatment.

BACKGROUND: The efficacy and side effects of voriconazole plus 5-flucytosine (Vori + 5-FC) versus amphotericin B deoxycholate plus 5-flucytosine (AmBd + 5-FC) as an induction treatment for cryptococcal meningitis are unknown. METHODS: Forty-seven patients treated with Vori + 5-FC and 92 patients treated with AmBd + 5-FC were included in the current study after propensity score matching (PSM) at a ratio of 1:2. Two-week laboratory test results and 90-day mortality were compared between the two groups. RESULTS: After 2 weeks of induction treatment, the CSF Cryptococcus sterile culture rate was 57.1% in the Vori + 5-FC group and 76.5% in the AmBd + 5-FC group (p = .026). No difference was found in the normalization of CSF indicators (glucose, total protein, intracranial pressure and India ink sterile rate) between the two groups. Both the Vori + 5FC regimen and AmBd + 5-FC regimen obviously decreased haemoglobin concentrations, platelet counts and serum potassium levels (all p ≤ .010). Notably, the Vori + 5FC regimen did not influence serum creatinine levels (p = .263), while AmBd + 5FC increased serum creatinine levels (p = .019) after 2-week induction treatment. The Vori + 5-FC group and AmBd + 5-FC group had similar 90-day cumulative survival rates (89.9% vs. 87.8%, p = .926). CONCLUSION: The Vori + 5-FC regimen was associated with low 2-week CSF sterile culture and was not superior to AmBd + 5-FC as induction therapy in terms of the 90-day cumulative survival rate of CM patients.

Ultrapermeable Gel Membranes Enabling Superior Carbon Capture.

Membrane technology is rapidly gaining broad attraction as a viable alternative for carbon capture to mitigate increasingly severe global warming. Emerging CO2 -philic membranes have become crucial players in efficiently separating CO2 from light gases, leveraging their exceptional solubility-selectivity characteristics. However, economic and widespread deployment is greatly dependent on the boosted performance of advanced membrane materials for carbon capture. Here, we design a unique gel membrane composed of CO2 -philic molecules for accelerating CO2 transportation over other gases for ultrapermeable carbon capture. The molecular design of such soft membranes amalgamates the advantageous traits of augmented permeation akin to liquid membranes and operational stability akin to solid membranes, effectively altering the membrane's free volume characteristics validated by both experiments and molecular dynamics simulation. Surprisingly, gas diffusion through the free-volume-tuned gel membrane undergoes a 9-fold improvement without compromising the separation factor for the superior solubility selectivity of CO2 -philic materials, and CO2 permeability achieves a groundbreaking record of 5608 Barrer surpassing the capabilities of nonfacilitated CO2 separation materials and exceeding the upper bound line established in 2019 even by leading-edge porous polymer materials. Our designed gel membrane can maintain exceptional separation performance during prolonged operation, enabling the unparalleled potential of solubility-selective next-generation materials towards sustainable carbon capture.

Severe anemia, severe leukopenia, and severe thrombocytopenia of amphotericin B deoxycholate-based induction therapy in patients with HIV-associated talaromycosis: a subgroup analysis of a prospective multicenter cohort study.

BACKGROUND: This study's objective was to investigate the predictors for severe anemia, severe leukopenia, and severe thrombocytopenia when amphotericin B deoxycholate-based induction therapy is used in HIV-infected patients with talaromycosis. METHODS: A total of 170 HIV-infected patients with talaromycosis were enrolled from January 1st, 2019, to September 30th, 2020. RESULTS: Approximately 42.9%, 20.6%, and 10.6% of the enrolled patients developed severe anemia, severe leukopenia, and severe thrombocytopenia, respectively. Baseline hemoglobin level < 100 g/L (OR = 5.846, 95% CI: 2.765 ~ 12.363), serum creatinine level > 73.4 µmol/L (OR = 2.573, 95% CI: 1.157 ~ 5.723), AST/ALT ratio > 1.6 (OR = 2.479, 95% CI: 1.167 ~ 5.266), sodium level ≤ 136 mmol/liter (OR = 4.342, 95% CI: 1.747 ~ 10.789), and a dose of amphotericin B deoxycholate > 0.58 mg/kg/d (OR = 2.504, 95% CI:1.066 ~ 5.882) were observed to be independent risk factors associated with the development of severe anemia. Co-infection with tuberculosis (OR = 3.307, 95% CI: 1.050 ~ 10.420), and platelet level (per 10 × 109 /L) (OR = 0.952, 95% CI: 0.911 ~ 0.996) were shown to be independent risk factors associated with the development of severe leukopenia. Platelet level < 100 × 109 /L (OR = 2.935, 95% CI: 1.075 ~ 8.016) was identified as the independent risk factor associated with the development of severe thrombocytopenia. There was no difference in progression to severe anemia, severe leukopenia, and severe thrombocytopenia between the patients with or without fungal clearance at 2 weeks. 10 mg on the first day of amphotericin B deoxycholate was calculated to be independent risk factors associated with the development of severe anemia (OR = 2.621, 95% CI: 1.107 ~ 6.206). The group receiving a starting amphotericin B dose (10 mg, 20 mg, daily) exhibited the highest fungal clearance rate at 96.3%, which was significantly better than the group receiving a starting amphotericin B dose (5 mg, 10 mg, 20 mg, daily) (60.9%) and the group receiving a starting amphotericin B dose (5 mg, 15 mg, and 25 mg, daily) (62.9%). CONCLUSION: The preceding findings reveal risk factors for severe anemia, severe leukopenia, and severe thrombocytopenia. After treatment with Amphotericin B, these severe adverse events are likely unrelated to fungal clearance at 2 weeks. Starting amphotericin B deoxycholate at a dose of 10 mg on the first day may increase the risk of severe anemia but can lead to earlier fungal clearance. TRIAL REGISTRATION: ChiCTR1900021195. Registered 1 February 2019.

Superoleophilic conjugated microporous polymer nano-surfactants for realizing unprecedented fast recovery of volatile organic compounds.

A pervaporation membrane with fast and selective permeation is key to improving the recovery efficiency of volatile organic compounds from water. Here, we synthesize a new type of nanofiller-conjugated microporous polymer (CMP) to fabricate polydimethylsiloxane (PDMS)-based mixed matrix membranes (MMMs) and explore their application in the recovery of organic solvents from water via pervaporation. Due to their good dispersibility in the dope solvent and compatibility with PDMS, uniform MMMs without discrete particle phases or aggregates are prepared. Interestingly, CMP nanosheets play a unique role as a nano-surfactant in enhancing both the sorption and diffusion coefficients, realizing unprecedented fast recovery of organic solvents from water. The total flux of the as-fabricated membranes can be enhanced from 74.8 to 406.2 kg µm-2 h-1 and the separation factor αethyl acetate/water is increased from 118.7 to 526.6 when using 5 wt% ethyl acetate aqueous solution as the feed at 50 °C. In addition, the CMP-incorporated PDMS membranes are also effective in recovering a wide range of organic compounds from water, including ethanol, acetone, tetrahydrofuran and acetonitrile.

Effect of modified high-flow oxygen therapy on positive end-expiratory pressure and end-expiratory lung volume based on simulated lung platform.

Objective: The aim of this study was to assess the effect of modified high-flow oxygen therapy on end-expiratory lung volume (EELV) and positive end-expiratory pressure (PEEP) in tracheotomized patients with normal pulmonary, acute hypoxic respiratory failure (AHRF) or chronic obstructive pulmonary disease (COPD). Methods: A ventilator and an artificial lung model were used to simulate the normal or strong inspiratory effort state of normal lung, AHRF and COPD patients. The traditional high-flow respiratory humidification therapy device connected with a standard interface (group A), and the modified therapy device added two types of resistance valves (group B, inner diameter 7.7 mm, length 24.0 mm; group C, inner diameter 7.7 mm, length 34.0 mm) to the exhalation end of the standard interface. The changes of end-expiratory lung volume (ΔEELV) and PEEP with the increase of flow rate (10 L/min, 20 L/min, 30 L/min, 40 L/min, 50 L/min, 60 L/min) in the three groups was recorded. Results: Under simulated conditions of normal lung, AHRF and COPD, as the flow rate increased by using the modified therapy device, the PEEP values in all groups showed an exponential increasing trend, and the ΔEELV also increased accordingly. In addition, under the same flow rate level, the PEEP values of the two modified high-flow oxygen therapies (Group B and Group C) were significantly higher than those of the standard high-flow oxygen therapy (Group A) (p < 0.05). In the normal lung model with normal or strong inspiratory effort, and in the AHRF or COPD model with strong inspiratory effort, when the flow rate was higher than 30 L/min, the PEEP levels of Group B were significantly lower than those of Group C (p < 0.05). In the AHRF model with normal inspiratory effort, when the flow rate was between 10 L/min and 60 L/min, the PEEP levels of Group B were significantly lower than those of Group C (p < 0.05). Moreover, in the COPD model with normal inspiratory effort, the PEEP levels of Group B were significantly lower than that of Group C only when the flow rate was 60 L/min (p < 0.05). Conclusion: The addition of different types of resistance valves to the high-flow exhalation end may be a feasible solution to improve the clinical efficacy of tracheotomized high-flow oxygen therapy.

Efficacy and safety of ainuovirine versus efavirenz combination therapies with lamivudine/tenofovir disoproxil fumarate for medication of treatment-naïve HIV-1-positive adults: week 48 results of a randomized controlled phase 3 clinical trial followed by an open-label setting until week 96.

Background: Ainuovirine (ANV) is a new non-nucleoside reverse transcriptase inhibitor (NNRTI), which was initially synthesized in Korea and later further developed in both Korea and China. Methods: A randomized, double-blind, double-dummy, positive parallel group, non-inferiority, phase 3 trial was conducted in 7 sites across China. Eligible HIV-1-positive antiretroviral therapy (ART)-naïve adults aged 18-65 years were randomly assigned in a 1:1 ratio to receive tenofovir disoproxil fumarate and lamivudine (TDF+3TC) in combination with either ANV (ANV group) or efavirenz (EFV group) for up to 48 weeks. Subsequently, participants in both groups received one of the two drug combinations according to their choice until week 96 in an observational study under an open-label setting. The primary endpoint was the proportion of participants achieving HIV RNA <50 copies/mL at week 48, with non-inferiority pre-specified at a margin of 10%. The secondary efficacy endpoints were logarithmic changes in HIV RNA, percentage of participants with HIV RNA levels ≤400 copies/mL and changes in the CD4 T-cell count after 48 and 96 weeks of treatment, as well as the percentage of participants with HIV RNA levels <50 copies/mL at 96 weeks of treatment. Safety endpoints were the incidence of adverse events and laboratory abnormalities evaluated according to the Division of AIDS criteria. This study was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR1800019041). Findings: Between November 27, 2018 and March 11, 2021, a total of 826 participants were screened, and 630 were finally enrolled and randomly assigned (1:1) to either ANV (n = 315) or EFV (n = 315) groups. The mean age was 30.6 ± 9.4 years and most participants were male (94.6%). At week 48, 274 (87.0%) of 315 participants in the ANV group and 288 (91.7%) of 314 in the EFV group achieved HIV-1 RNA <50 copies/mL and non-inferiority was established (difference: -4.7%, 95% CI: -9.6 to 0.1%). In the period, 293 participants continued to take the ANV regimen and 287 switched from the EFV to the ANV regimen. During the open-label period, 92.5% (271/293) of participants in the continued ANV group and 95.1% (273/287) in the ANV to EFV transfer group remained virologically suppressed (HIV-1 RNA <50 copies/mL) at week 96 (p = 0.189). The incidence of NNRTI treatment-related adverse events (TEAEs) at week 48 was 67.6% in 315 participants in the ANV group, which was significantly lower than in 91.4% of 314 participants in the EFV group (p < 0.001). The most common TEAEs (weeks 0-48) were dizziness (10.5%) and dyslipidemia (22.2%) in the ANV group vs. 51.0% and 34.4% in the EFV group, respectively, followed by transaminase elevation (9.2% vs. 29.0%), γ-glutamyl transferase elevation (8.3% vs. 19.1%), and rash (7.9% vs. 18.8%) (all p < 0.001). After switching from EFV to ANV, TEAEs in the former EFV participants were significantly reduced in the following observational period of 48-96 weeks. Interpretation: The week 48 results indicated that the efficacy of ANV was non-inferior to EFV when combined with two NRTIs. The per-protocol risk difference at week 48 for the primary endpoint also supported non-inferiority. TEAEs in ANV treated participants were less frequent with regard to liver toxicity, dyslipidemia, neuropsychiatric symptoms and rash compared to the EFV group during the first 48 weeks of therapy. The effects were maintained during the 48-96 weeks of therapy. Funding: Jiangsu Aidea Pharmaceutical Co., Ltd.

Artificial Intelligence in Intensive Care Medicine: Toward a ChatGPT/GPT-4 Way?

Although intensive care medicine (ICM) is a relatively young discipline, it has rapidly developed into a full-fledged and highly specialized specialty covering several fields of medicine. The COVID-19 pandemic led to a surge in intensive care unit demand and also bring unprecedented development opportunities for this area. Multiple new technologies such as artificial intelligence (AI) and machine learning (ML) were gradually being applied in this field. In this study, through an online survey, we have summarized the potential uses of ChatGPT/GPT-4 in ICM range from knowledge augmentation, device management, clinical decision-making support, early warning systems, and establishment of intensive care unit (ICU) database.

Potential Use of Artificial Intelligence in Infectious Disease: Take ChatGPT as an Example.

Over the past month, a new AI model called Chatbot Generative Pre-trained Transformer (ChatGPT), has received enormous attention in the media and scientific communities due to its ability to process and respond to commands in a humanistic fashion. As reported, five days after its launch, the number of registered users of ChatGPT exceeded one million, and its monthly active users had exceeded 100 million two months later, making it the most rapidly growing consumer application in history. The advent of ChatGPT has further brought about new ideas and challenges in the realm of infectious disease. In view of this, in order to evaluate the potential use of ChatGPT in clinical practice and scientific research of infectious disease, we conducted a brief online survey by using the publicly available ChatGPT webpage. Also, the present study also talks about the relevant social and ethical issues related to this program.

Artificial Intelligence in Sports Medicine: Could GPT-4 Make Human Doctors Obsolete?

Sports medicine, an essential branch of orthopedics, focuses on preserving, restoring, improving, and rebuilding the function of the human motor system. As a thriving interdisciplinary field, sports medicine attracts not only the interest of the orthopedic community, but also artificial intelligence (AI). In this study, our team summarized the potential applications of GPT-4 in sports medicine including diagnostic imaging, exercise prescription, medical supervision, surgery treatment, sports nutrition, and science research. In our opinion, it is impossible that GPT-4 could make sports physicians obsolete. Instead, it could become an indispensable scientific assistant for sport doctors in future.

Exploring the Potential of GPT-4 in Biomedical Engineering: The Dawn of a New Era.

Biomedical engineering is a relatively young interdisciplinary field based on engineering, biology, and medicine. Of note, the rapid progress of artificial intelligence (AI)-based technologies has made a significant impact on the biomedical engineering field, and continuously bring innovations and breakthroughs. Recently, ChatGPT, an AI chatbot developed by OpenAI company, has gained tremendous attention due to its powerful natural language generation and understanding ability. In this study, we explored potential of GPT-4 in the eight branches of biomedical engineering including medical imaging, medical devices, bioinformatics, biomaterials, biomechanics, gene and cell engineering, tissue engineering, and neural engineering. Our results show that the application of GPT-4 will bring new opportunities for the development of this field.

Talk with ChatGPT About the Outbreak of Mpox in 2022: Reflections and Suggestions from AI Dimensions.

In the era of big data, generative artificial intelligence (AI) models are currently in a boom. The Chatbot Generative Pre-trained Transformer (ChatGPT), a large language model (LLM) developed by OpenAI (San Francisco, CA), is a type of AI software that could generate text based on the input it receives. In this study, in order to explore how ChatGPT could give reflections and suggestions about the sudden outbreak of Mpox in 2022 from the AI dimensions, our group talked with ChatGPT with several questions about Mpox. We hope this talk could enrich our knowledge on Mpox from the new AI dimensions and also explore the possibility of human and AI fight shoulder to shoulder for prevention and containment of the potential epidemics or pandemics in future.

Synergistic sulfonamides plus clindamycin as an alternative therapeutic regimen for HIV-associated Toxoplasma encephalitis: a randomized controlled trial.

BACKGROUND: The preferred therapeutic regimen for Toxoplasma encephalitis (TE) is a combination of pyrimethamine and sulfadiazine, and trimethoprim-sulfamethoxazole (TMP-SMX) plus azithromycin is the widespread alternative therapeutic regimen. The synergistic sulfonamides tablet contains TMP, sulfadiazine, and SMX and hypothetically could be used for TE treatment. This study aimed to compare the efficacy and safety of synergistic sulfonamides plus clindamycin (regimen B) with TMP-SMX plus azithromycin (regimen A) for the treatment of human immunodeficiency virus (HIV) associated TE. METHODS: This was an open-labeled, multi-center randomized controlled trial recruited from 11 centers. Each recruited patient was randomly assigned to receive regimen A or regimen B for at least 6 weeks. The overall response was evaluated by assessment of the clinical response of TE-associated clinical features and the radiological response of TE-associated radiological findings. The overall response rate, clinical response rate, radiological response rate, and adverse events were assessed at 2, 6, and 12 weeks. Death events were compared between the two regimens at 6, 12, and 24 weeks. RESULTS: A total of 91 acquired immunodeficiency syndrome (AIDS)/TE patients were included in the final analysis (44 in regimen A vs . 47 in regimen B). The overall response rate, which refers to the combined clinical and radiological response, was 18.2% (8/44) for regimen A and 21.3% (10/47) for regimen B at week 6. The results of clinical response showed that, in comparison with regimen A, regimen B may perform better with regards to its effect on the relief of clinical manifestations (50.0% [22/44] vs . 70.2% [33/47], P = 0.049). However, no significant differences in radiological response, mortality events, and adverse events were found between the two regimens at week 6. CONCLUSIONS: Synergistic sulfonamides plus clindamycin, as a novel treatment regimen, showed no significantly different efficacy and comparable safety in comparison with the TMP-SMX plus azithromycin regimen. In addition, the regimen containing synergistic sulfonamides may exhibit advantages in terms of clinical symptom alleviation. TRIAL REGISTRATION: ChiCTR.org.cn, ChiCTR1900021195.

Emerging trends and research foci of oncolytic virotherapy for central nervous system tumors: A bibliometric study.

Background: Central nervous system tumor (CNST) is one of the most complicated and lethal forms of human tumors with very limited treatment options. In recent years, growing evidence indicates that oncolytic virotherapy (OVT) has emerged as a promising therapeutic strategy for CNSTs. And a considerable amount of literature on OVT-CNSTs has been published. However, there are still no studies summarizing the global research trends and hotspots of this field through a bibliometric approach. To fulfill this knowledge gap, bibliometric analysis was conducted based on all publications relating to OVT-CNSTs since 2000s. Methods: We searched the Web of Science Core Collection for all relevant studies published between 2000 and 2022. Four different tools (online analysis platform, R-bibliometrix, CiteSpace and VOSviewer) were used to perform bibliometric analysis and network visualization, including annual publication output, active journals, contribution of countries, institutions, and authors, references, as well as keywords. Results: A total of 473 articles and reviews were included. The annual number of publications on OVT-CNSTs showed a significant increasing trend. Molecular Therapy and Cancer Research were the most active and co-cited journals, respectively. In terms of contributions, there is no doubt that the United States occupied a leading position with the most publications (n=307, 64.9%) and the highest H-index (57). The institution and author that contributed the largest number of publications were Ohio State University and Chiocca EA, respectively. As can be seen from citation analysis, the current studies mainly focused on preclinical and phase I/II clinical results of various oncolytic virus for CNSTs treatment. Keywords co-occurrence and burst analysis revealed that the following research topics including immunotherapy, T-cells, tumor microenvironment, vaccine, blood-brain-barrier, checkpoint inhibitors, macrophage, stem cell, and recurrent glioblastoma have been research frontiers of this field and also have great potential to continue to be research hotspots in the future. Conclusion: There has been increasing attention on oncolytic viruses for use as CNSTs therapeutics. Oncolytic immunotherapy is a topic of great concern in this field. This bibliometric study provides a comprehensive analysis of the knowledge base, research hotspots, development perspective in the field of OVT-CNSTs, which could become an essential reference for scholars in this area.

Initiating antiretroviral therapy within 2 weeks of anti-Pneumocystis treatment does not increase mortality or AIDS-defining events in patients with HIV-associated moderate to severe Pneumocystis pneumonia: results of a prospective observational multicenter study.

BACKGROUND: The mortality rate remains high among patients with coinfection with Pneumocystis pneumonia (PCP) and HIV. The timing for initiation of antiretroviral therapy (ART) after a diagnosis of moderate to severe PCP remains controversial, however. We therefore designed the present study to determine the optimal timing for ART initiation in AIDS-associated PCP (AIDS/PCP) patients. METHODS: This was a multicenter, observational, prospective clinical trial. Eligible participants were recruited from 14 hospitals in mainland China, and assigned to an Early ART arm (initiation of ART ≤ 14 days after PCP diagnosis) and a Deferred ART arm (initiation of ART > 14 days after PCP diagnosis). The primary outcomes were death and the incidence of AIDS-defining events at week 48. The secondary outcomes were the changes in CD4+ T-cell counts from baseline values at weeks 12, 24, and 48, the virological suppression rate at week 24 and week 48, the rate of development of PCP-associated immune reconstitution inflammatory syndrome (PCP/IRIS), and the rate of adverse events over 48 weeks. RESULTS: The present study was performed using the data of 363 participants, with 169 participants in the Early ART arm, and 194 participants in the Deferred ART arm. Immunological and virological outcomes were found to be similar in both treatment arms. At week 48, there were no significant differences for the incidence of mortality (20 vs. 26, p = 0.860), and AIDS-defining events (17 vs. 26, p = 0.412). Over 48 weeks, the rates of PCP/IRIS (2 vs. 3, p = 1.000), adverse events (70 vs. 72, p = 0.465), and grade 3 or 4 adverse events (28 vs. 34, p = 0.919) did not reach statistical significance. A significant difference observed between two study arms was that 11 participants (55.0%) in the Early ART arm compared to 23 participants (88.5%) in the Deferred ART arm (p = 0.026) succumbed before ART had ever been started. CONCLUSIONS: Early ART initiation results in no increase in mortality, AIDS-defining events, IRIS, adverse events, and immunological or virological outcomes. These results support the early initiation of ART in patients with moderate to severe AIDS/PCP. Clinical trial registration The present trial was registered at Chinese Clinical Trial Registry (ChiCTR1900021195). Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 .