Background: People living with HIV (PLWH) constitute a vulnerable population during the COVID-19 pandemic; however, it remains uncertain whether long-term suppressive antiretroviral therapy (ART) restores sufficient immune competence to support robust hybrid immunity. While vaccination followed by breakthrough infection—termed hybrid immunity—typically elicits potent humoral responses in immunocompetent individuals, the functional quality and breadth of these responses against evolving Omicron subvariants remain poorly characterized in PLWH. This study aimed to assess functional antibody responses, including neutralizing activity and Fc effector functions, in vaccinated and unvaccinated PLWH who experienced breakthrough infection with Omicron subvariants BA.4/5 or BF.7. Methods: We enrolled three cohorts between December 5 and December 20, 2022: 25 HIV-negative individuals with breakthrough infection (BTI-HC), 20 ART-experienced PLWH with breakthrough infection following three-dose COVID-19 vaccination (BTI-HIV), and 10 ART-experienced PLWH with primary infection without prior vaccination (PI-HIV). All HIV-positive participants were receiving suppressive ART with regimens based on non-nucleoside reverse transcriptase inhibitors or integrase strand transfer inhibitors for a median of 3.4 years. We measured receptor-binding domain (RBD)-specific IgG, neutralizing antibody titers against ancestral D614G, Delta, BA.1, BA.4/5, BF.7, XDV, KP.2, and KP.3 variants, and antibody-dependent cellular cytotoxicity (ADCC) responses. Results: Despite lower absolute CD4+ T cell counts, BTI-HIV participants mounted RBD-binding IgG, neutralizing antibody, and ADCC responses that were comparable to BTI-HC and significantly exceeded PI-HIV across all tested variants. Both breakthrough infection cohorts exhibited immunological imprinting, with higher neutralizing titers against ancestral D614G than infecting BA.4/5 or BF.7 variants. Emerging variants XDV, KP.2, and KP.3 demonstrated substantial neutralization escape in all groups. PI-HIV showed markedly diminished neutralization breadth and failed to generate enough responses against all tested Omicron strains. Conclusions: Suppressive ART enables PLWH to mount hybrid immunity—conferred by vaccination followed by BF.7 or BA.4/5 breakthrough infection—with neutralizing and ADCC responses comparable to HIV-negative individuals, and significantly exceeding those of unvaccinated PLWH with primary infection. This underscores the critical role of vaccination in establishing effective hybrid immunity in this population. However, we observed immunological imprinting, with higher titers against ancestral strains than against infecting variants, and substantial escape by emerging sublineages XDV, KP.2, and KP.3 across all groups. These findings support prioritizing updated variant-containing vaccines for HIV-positive populations and reinforce the essential role of vaccination in this vulnerable group.

Azvudine (FNC) is a 2'-β-fluoro-4'-azidocytidine analog being investigated as a next-generation nucleoside reverse transcriptase inhibitor (NRTI). To address the treatment failure and rapid resistance emergence posed by HIV-1 variants, we evaluated FNC's resistance profile and structural rationale. Using site-directed mutagenesis, a panel of clinically relevant HIV-1 RT mutants was constructed to assess FNC's resistance profile and mechanistic behavior. FNC exhibited sub-nanomolar potency (EC50 = 0.0812-0.1596 nM) across diverse HIV-1 subtypes, achieving up to 3000-fold higher antiviral activity than lamivudine (3TC) and emtricitabine (FTC). Unlike clinically used NRTIs, FNC retained or enhanced potency against most strains harboring key resistance mutations (K65R, Y115F, TAMs, Q151M, and T69 insertion mutations) except for M184V and M184I amino acid substitutions. FNC also showed superior intracellular persistence and, accordingly, reduced both the proportion of HIV-infected cells and the copy number of intact proviral DNA more effectively than 3TC and FTC. Furthermore, FNC showed more pronounced synergy in the common clinical combination therapies via replacing their nucleoside drugs. Structural modeling and molecular dynamics simulations suggest that the 2'-fluoro and 4'-azido substituents formed extra interactions with the catalytic site via hydrogen bonding, hydrophobic contacts, and Mg2+ coordination. These interactions provide a plausible structural basis for the retained potency against resistant mutants by stabilizing the catalytic complex, reducing excision, and impeding strand translocation. Collectively, these findings identify FNC as a structurally optimized cytidine analogue with broad activity against clinically relevant resistance variants, highlighting its potential as a promising candidate for next-generation HIV-1 therapy.

Doravirine (DOR)-containing antiretroviral therapy (ART) has been recommended as first-line ART by China treatment guidelines since 2021. However, Real-world studies on DOR in China are scarce. We evaluated the real-world effectiveness of DOR-containing ART in Chinese people with HIV-1 (PWH), including treatment-naïve people regardless of viral load (VL) at baseline and treatment-experienced people regardless if they were virologic suppression (VS) or not. This was a retrospective, multicenter, observational study using medical chart review in seven hospitals, covering top-tier infectious disease hospitals across regions in China. All the participants who initiated DOR-containing ART during August 2021 and September 2023 were included and followed until September 2024. At baseline, higher proportions of the 352 participants were male (84.9

BACKGROUND:Although the high efficacy and safety of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and dolutegravir/lamivudine (DTG/3TC) in treatment-naïve people living with HIV (PLWH) have been well established, their metabolic effects remain a concern. RESEARCH DESIGN AND METHODS:We retrospectively analyzed 499 treatment-naïve PLWH who initiated BIC/FTC/TAF or DTG/3TC at Beijing Ditan Hospital between January 2021 and December 2023 to compare metabolic outcomes over a 48-week follow-up period. RESULTS:Compared to DTG/3TC, the BMI at week 48 was higher in participants receiving BIC/FTC/TAF (24.65 vs. 23.14 kg/m2, p = 0.023) after propensity score matching, with a greater increase from baseline (+1.10 vs. +0.71 kg/m2, p = 0.011). PLWH receiving BIC/FTC/TAF exhibited an increase in uric acid over 48 weeks (median change 5 μmol/L vs. -6 μmol/L, adjusted change p = 0.034). No significant between-group differences were observed in the changes of lipid, glucose and renal parameters over 48 weeks. Both regimens achieved similar virologic suppression (95.5% vs. 94.5%, p = 0.857) and comparable CD4 recovery (+188 vs. +173 cells/μL, p = 0.726). CONCLUSION:In this cohort of treatment-naïve PLWH, initiation of BIC/FTC/TAF or DTG/3TC achieved comparable metabolic outcomes, immunologic and virologic after 48 weeks, while BIC/FTC/TAF was associated with significantly increases in BMI.

Incomplete immune reconstitution (IIR) is a serious complication affecting 10 to 40% of people living with HIV (PLWH) despite effective antiretroviral therapy, leading to increased morbidity and mortality. Current risk prediction models rely on single-time point measurements and lack dynamic assessment capabilities. We developed a dynamic joint prediction system for IIR risk (DJPSIIR) using Bayesian joint modeling to analyze longitudinal data from 21,862 PLWH across 31 Chinese provinces (2003-2024). The system integrates continuous CD4+ T cell counts and CD4/CD8 ratios with clinical parameters to generate real-time risk predictions. DJPSIIR demonstrated strong discriminatory performance with area under receiver operating characteristic curves of 0.890 to 0.912 for 5- to 7-year predictions, consistently outperforming expert assessments and 19 machine learning algorithms across multiple validation cohorts. Our dynamic prediction system enables precise identification of high-risk individuals and could transform clinical decision-making by facilitating timely interventions to prevent IIR progression in HIV care.

Monkeypox virus (MPXV), a zoonotic orthopoxvirus (OPXV), re-emerged as a global public health concern following the 2022 multi-country outbreak that disproportionately affected people with human immunodeficiency virus (HIV). In July 2023, the U.S. National Institutes of Health classified MPXV as an AIDS-defining opportunistic infection, underscoring the urgency of understanding immune features in immunocompromised populations. Existing studies provide limited data on the durability and coordination of MPXV-specific humoral and cellular immunity in people with HIV (PWH). Moreover, whether concomitant MPXV infection modulates HIV-specific immunity in PWH remains unclear. We aimed to evaluate the durability of immune responses against MPXV, compare immune profiles between PWH and people without HIV (PWoH), and assess the impact of MPXV coinfection on HIV-specific immunity. We conducted a prospective immunological analysis involving 28 PWH and 13 PWoH with confirmed MPXV infection. Peripheral blood samples were collected at 1–2 weeks, 1–6 months, and 12–18 months post-infection. Plasma IgG levels against MPXV antigens were measured using ELISA. Poxvirus- and HIV-specific memory T (Tm) cell responses were assessed using activation-induced marker and intracellular cytokine staining assays via flow cytometry. MPXV infection elicited durable humoral and cellular immune responses for up to 18 months, regardless of HIV status. However, PWH demonstrated attenuated MPXV-specific antibody responses, lower frequencies of poxvirus-specific Tm cells, and reduced polyfunctionality compared to PWoH. Notably, immune coordination in PWH was impaired, as evidenced by weakened concordance between humoral and cellular responses, disrupted interactions between CD4+ and CD8+ Tm cell subsets, and diminished consistency among antibody levels. Additionally, HIV-specific Tm cell responses remained stable in antiretroviral-treated PWH, irrespective of prior MPXV infection. MPXV infection induced long-lasting cellular and humoral immunity in both PWH and PWoH. However, HIV-mediated immune dysregulation compromised the strength and coordination of these responses.

Advances in antiretroviral therapy (ART) have extended the life expectancy of people living with HIV (PLHIV). The long-term goals of ART for PLHIV were better medication convenience and fewer side effects. The development of the Internet and increased education allow PLHIV to understand evolving and optimized regimens and participated in decision-making. Understanding ART switching patterns can help identify key populations for medical institutions or social organizations’ publicity and education. This cross-sectional study recruited PLHIV (≥ 18 years) receiving ART at the Hospital’s outpatient clinic between February 13 and October 26, 2023. Social characteristics, ART switching patterns, and health education-related information were collected. The patient-driven switching pattern was defined as PLHIV volunteering to switch treatment regimens, while the physician-driven pattern was described as doctors suggesting regimen switches based on routine test results. Multinomial regression was used to explore factors associated with ART switching patterns. Out of 1877 PLHIV analyzed, 93.98

OBJECTIVES:Incomplete immune reconstitution (IIR) affects 10-40% of people living with HIV (PLWH) despite suppressive antiretroviral therapy (ART), increasing morbidity and mortality. We investigated whether baseline triglyceride-glucose index (TYG), a marker of insulin resistance, predicts long-term IIR risk in PLWH. METHODS:This multicentre retrospective cohort study analyzed 11076 PLWH from three Chinese HIV centers (2009-2020) using a 4-year landmark design. IIR was defined as CD4 <350 cells/μl after >4 years of ART with sustained virological suppression. Center-stratified Cox models with time-varying effects estimated hazard ratios (HRs) for TYG. RESULTS:Over a median follow-up of 7.74 years, higher baseline TYG was associated with a lower risk of IIR. There was borderline evidence of a stronger inverse association over time (P = 0.080), with the HR decreasing from 0.795 (95% CI: 0.733-0.862) at year 5 to 0.733 (95% CI: 0.639-0.842) at year 10. Results remained robust across sensitivity analyses. The association was more pronounced in younger participants (<60 years), those with better baseline immune status (CD4 ≥200 cells/µl, WHO stage I/II), virological suppression, favorable lipid profiles, and higher hemoglobin levels. CONCLUSIONS:Baseline TYG may aid risk stratification for IIR in PLWH.

Objectives : Low-frequency HIV-1 drug resistance mutations (DRMs) and mutation linkage within viral genomes may contribute to treatment failure and multidrug resistance but are difficult to resolve using conventional sequencing. We evaluated the performance of nanopore long-read sequencing for HIV-1 DRM detection and haplotype analysis. Methods : In this retrospective study, 230 plasma samples from people living with HIV undergoing resistance testing at Beijing Ditan Hospital between Aug 2024 and July 2025 were analysed using the nanopore-based G-seq500 platform. DRM profiles and subtype classifications were compared with Sanger sequencing, and discordant mutations were validated by next-generation sequencing (NGS, DNBSEQ-T7 platform). Long-read data were further used for haplotype reconstruction. Results : The overall concordance rate between G-seq500 and Sanger sequencing for DRM detection was 93.0%. Additional resistance-associated mutations identified by G-seq500 were confirmed by NGS and were predominantly low-frequency variants. Subtyping concordance was 92.2% (212/230). Haplotype reconstruction revealed substantial intra-host viral diversity, with nearly half of samples containing multiple viral haplotypes. Multiple DRMs frequently co-occurred within the same haplotype, indicating linked multidrug-resistant viral populations. Conclusions : G-seq500 sequencing showed comparable performance to Sanger sequencing for HIV-1 DRM detection and subtype classification. Long-read sequencing further enabled characterization of low-frequency resistance-associated variants and within-host viral haplotype structures, providing additional insights into the complexity of HIV-1 drug resistance beyond conventional consensus sequencing.

Background:This study evaluated the diagnostic value of metagenomic next-generation sequencing (mNGS) in identifying pathogens causing pulmonary infections in 64 acquired immunodeficiency syndrome (AIDS) patients at Beijing Ditan Hospital. Methods:Bronchoalveolar lavage fluid (BALF) samples were analyzed using mNGS and conventional microbiological tests (CMT). Diagnostic performance was compared, and random forest analysis was used to assess pathogenicity. Results:mNGS detected 45 pathogens, including 14 viruses, 3 fungi, and 28 bacteria. Compared with CMT, mNGS showed higher sensitivity for detecting bacteria (75.0% vs 29.17%), fungi (45.0% vs 16.67%), and viruses (80.0% vs 20.83%). Mixed infections were identified in 55.2% of cases, predominantly Pneumocystis pneumonia (PCP) with bacterial coinfections. However, mNGS had lower concordance with CMT for viruses (24.1% for cytomegalovirus) and Mycobacterium tuberculosis (75.0%). Random forest analysis highlighted Candida albicans and Stenotrophomonas maltophilia as highly pathogenic. Conclusions:While mNGS demonstrated superior broad-spectrum detection, its limitations in viral and TB diagnosis underscore the need for optimized protocols. The study supports mNGS as a complementary tool for diagnosing complex pulmonary infections in AIDS patients, enhancing precision medicine but requiring further refinement for widespread clinical adoption.

BACKGROUND:Recent findings on the outbreak of mpox indicate that immunosuppressed people are at significantly higher risk of death. The aims of the research were to provide a summary of the clinical features of mpox fatal cases, explore the effects of immunosuppression, monkeypox virus (MPXV)/human immunodeficiency virus (HIV) co-infection, and delayed antiretroviral therapy (ART) on prognosis, and offer evidence-based recommendations to inform clinical practices. METHODS:Demographic information, detailed HIV disease characteristics, ART history, mpox clinical features, laboratory results, and radiological evaluations were retrospectively extracted from electronic medical records. RESULTS:Six fatal cases were men who have sex with men (MSM), with a median age of 35 years (range: 23-37 years). Their median CD4+ count was 51 cells/μL (range: 2-116 cells/μL). Of these cases, two were simultaneously diagnosed with MPXV/HIV infection, one was diagnosed with HIV infection and never initiated ART, and the other three had interrupted ART prior to mpox diagnosis. All patients started or restarted ART, with a medium time from initiation of ART to death being 52 days (range: 20-148 days). Besides such symptoms like skin lesions and lymphadenopathy, all of them developed severe complications, including bacterial co-infections (n = 5), pneumonia (n = 5), intestinal obstruction (n = 2), and ocular involvement (n = 3). The median intervals between symptom onset and hospitalization or death were 30 days (range: 6-36 days) and 59 days (range: 32-110 days), respectively, with all death being due to sepsis or related multiple organ failure. CONCLUSION:The combination of MPXV with advanced HIV infection carries an excessive risk of death, generated by severe immunodeficiency that facilitates serious secondary infections and MPXV dissemination. Even if ART is initiated as soon as possible, immune function cannot be restored quickly enough to clear MPXV.

Although highly active antiretroviral therapy (HAART) suppresses HIV viral load and extends life, rising non-AIDS-defining events (NADEs) underscore the importance of long-term health, including reproductive tract health in women living with HIV (WLWH). This study compared vaginal microbiota in WLWH versus women without HIV infection (WLWNH) to inform reproductive health assessment and intervention. Vaginal swabs from 76 WLWH and 74 WLWNH (Beijing Ditan Hospital, Sept-Oct 2022) underwent 16S rRNA gene sequencing. We used hierarchical clustering to categorize community state types (CSTs I–V) and Adonis for inter-group differences. Pearson correlation assessed relationships between CD4 + T cells and differential bacteria, while Spearman correlation evaluated microbial co-occurrence network interactions (visualized via Gephi0.10.1). Neutral community modeling evaluated assembly processes. WLWH exhibited higher vaginal microbial diversity. Compared to WLWNH, Gardnerella vaginalis showed higher relative abundance in WLWH CST III (P = 0.001). Additionally, urogenital pathogens Aerococcus christensenii and Ureaplasma urealyticum were significantly enriched in WLWH CST III (P = 0.028, P = 0.033; AUC = 0.704, 0.721, respectively) and CST IV (P = 0.024, P = 0.031; AUC = 0.657, 0.646, respectively). In CST III, CD4 + T cell counts correlated positively with Aerococcus christensenii (r = 0.49, P = 0.044). Neutral community modeling demonstrated that microbiota assembly in WLWH was primarily shaped by stochastic processes (R2 = 0.37 vs 0.219) with significantly restricted microbial dispersal (Nm = 9 vs14). WLWH exhibit a distinct, highly diverse vaginal dysbiosis enriched with anaerobic and urogenital pathogenic bacteria. This post-HIV infection dysbiosis may predispose women to subsequent genital infections; future longitudinal research comparing pre- and post-infection microbiome dynamics will be crucial for optimizing gynecological management.

BACKGROUND:Persistent low-level viremia (pLLV) remains clinically challenging among people living with HIV (PWH) receiving antiretroviral therapy (ART), and whether ART regimen switching improves virologic outcomes remains controversial. METHODS:We conducted a multicenter retrospective real-world cohort study across seven Chinese medical institutions. Adults with pLLV (50 copies/mL ≤ plasma viral load [VL] < 1000 copies/mL) were included and classified into a non-switch (control) group or a switch group based on the management decision of treating physicians at pLLV. The primary outcome was viral suppression at week 48; week 24 and week 96 suppression were secondary. Adjusted odds ratios (aOR) and risk differences (aRD) were estimated using logistic regression. Longitudinal viral load and CD4 trends were assessed using rank-based nonparametric longitudinal models. RESULTS:162 participants were included (97 control; 65 switch). Viral suppression at week 48 was 64.37% in the control group and 68.52% in the switch group (aOR 1.40, P = 0.427; aRD 0.07, P = 0.423). At week 24, suppression occurred in 40.98% and 50.00%, respectively (aOR 1.34, P = 0.521; aRD 0.07, P = 0.518). HIV RNA levels decreased and CD4 increased modestly over time in both groups without between-group differences. CONCLUSIONS:In this retrospective cohort, regimen switching after pLLV was not associated with improved virologic suppression.

In China, approximately 13% of people living with human immunodeficiency virus (HIV) (PLWH) are receiving lopinavir/ritonavir (LPV/r)-based regimens. These PLWH typically have a history of either treatment failure or intolerance to first-line efavirenz-based regimens. Given the considerable pill burden and adverse effects associated with LPV/r, treatment optimization is important for this population. This multicenter retrospective study aimed to evaluate the efficacy and safety of switching from LPV/r-based regimens to the single-tablet regimen of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Virological suppression rates (HIV-RNA < 40 copies/mL) were primarily compared between the 48-week periods before and after switching to BIC/FTC/TAF. CD4 counts and metabolic data were also assessed. A total of 461 PLWH were recruited between January 2021 and December 2023, with 92.2% being male, a median age of 38 years, and a median antiretroviral therapy duration of 8 years. Prior to initiating LPV/r, 23.0% (106/461) had documented virological failure. During LPV/r treatment, 18.9% (20/106) of these individuals experienced viral rebound. Among all participants, the overall virological suppression rates significantly increased from 94.6% (pre-switch) to 98.6% (post-switch) (P < 0.001). Notably, among participants with prior virological failure, suppression rates improved significantly from 81.1% to 97.2% (P < 0.001), whereas no significant difference was observed in those without such history (from 98.6% to 99.2%, P = 0.764). The median triglyceride level decreased from 2.4 mmol/L to 1.8 mmol/L (P < 0.001), while no difference in CD4 counts was observed. These findings demonstrate that BIC/FTC/TAF is an effective and metabolically favorable treatment option for PLWH switching from LPV/r based regimens, regardless of whether they have a prior history of virological failure.

Background:Mycobacterial infections represent a major cause of morbidity and mortality in HIV-infected individuals. This study evaluated diagnostic techniques for mycobacterial identification and compared clinicopathological features between HIV-positive and HIV-negative patients. Methods:We analyzed 88 tissue samples (with 41 matched blood and 28 sputum samples) using histopathology (HE and acid-fast staining), bacterial culture, MTB-PCR (sputum/biopsy), PCR-reverse dot blot hybridization (RDBH), and metagenomic pathogen detection technology (MetaPath™). Logistic regression analyses were performed to identify factors affecting detection rates. Results:Mycobacterial infection was detected in 95.5% (84/88) of patients. Among HIV-positive patients (n=63), 46% (29/63) had Mycobacterium tuberculosis (MTB) infections, and 44% (28/63) had non-tuberculous mycobacteria (NTM) infections, significantly higher than the 20% (5/25) NTM rate in HIV-negative patients. Univariate analysis identified HIV-positive status (p=0.009), lymph node involvement (p=0.020), and positive MetaPath™ results (p=0.002) as significant predictors of detection, while multivariate analysis confirmed these as independent factors (p=0.036; p=0.042; p=0.006). Lymph nodes were the most common infection site in HIV-positive patients (42.9%, 27/63), while lung tissue predominated in HIV-negative patients (48%, 12/25). MetaPath™ demonstrated superior sensitivity and specificity for detecting both MTB and NTM. Biopsy samples provided higher diagnostic accuracy than sputum or blood for lung and lymph node infections, but not for brain. In HIV-positive patients, NTM infections showed significantly more granuloma formation (p=0.032) and foam cells (p=0.005), but less necrosis (p=0.0005) compared to MTB infections. No significant differences were observed in HIV-negative patients. Conclusions:MetaPath™ is a highly effective diagnostic tool for mycobacterial infections, particularly in tissue biopsies. HIV-positive status, lymph node involvement, and MetaPath™ positivity independently predict mycobacterial detection. HIV-positive patients exhibit distinct clinicopathological features, emphasizing the need for tailored diagnostic and therapeutic approaches based on immune status.

Background:The WHO and international treatment guidelines recommend rapid initiation of antiretroviral therapy (ART) for all treatment-naive (TN) people living with human immunodeficiency virus (HIV) (PLWH). However, data on temporal trends and clinical outcomes of ART initiation and regimen selection among TN PLWH remain limited in China. This study is designed to evaluate the real-world effectiveness of contemporary treatment strategies within the Chinese context. Methods:We conducted a retrospective study of 1,460 TN PLWH who initiated ART between January 2021 and December 2023 at Beijing Ditan Hospital. Data on sex, age, initiation time, ART regimens, CD4 counts, and HIV viral load were collected. Initiation time was categorized based on the time from diagnosis to ART initiation: same-day initiation (0 days), rapid initiation (1 - 7 days), regular initiation (8 - 30 days), and delayed initiation (> 30 days). The main endpoint was the rate of PLWH with virological suppression (HIV-1 RNA < 40 copies/mL) during the study period. Additionally, the durability of ART regimens and the CD4 T-cell count recovery were also evaluated. Factors associated with regimen durability were assessed using univariate and multivariate Cox proportional hazards models. Generalized estimating equations (GEE) were used to identify factors associated with virological suppression among TN PLWH. Results:From 2021 to 2023, the proportion of patients with same-day initiation and that of patients with rapid initiation significantly increased, rising from 8.4% (55/656) to 14.0% (69/493) and from 49.5% (325/656) to 57.6% (284/493), respectively (P < 0.001). Furthermore, 32.9% (46/140) and 36.3% (269/741) of PLWH who underwent same-day and rapid initiation, respectively, chose initial regimens containing two nucleoside reverse transcriptase inhibitors plus a non-nucleoside reverse transcriptase inhibitor. A representative regimen was efavirenz, lamivudine, and tenofovir disoproxil fumarate (EFV+3TC+TDF). All patients achieved a viral suppression rate of over 95.0% at the 24- and 36-month follow-up visits. In TN PLWH who adhered to initial regimens, GEE analysis of virological suppression factors showed both bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and dolutegravir/lamivudine (DTG/3TC) were non-inferior to EFV+3TC+TDF (odds ratio [OR] = 1.34, 95% confidence interval [CI]: 0.75 - 2.39, P = 0.318; OR = 1.92, 95% CI: 0.54 - 6.80, P = 0.311, respectively). Moreover, BIC/FTC/TAF and DTG/3TC were associated with a lower likelihood of regimen switching, with hazard ratios of 0.35 (P < 0.001) and 0.39 (P  = 0.004). Besides, BIC/FTC/TAF achieved CD4 T cell counts above 350 cells/μL significantly earlier (P = 0.015). Conclusion:Our findings revealed the positive trend in rapid initiation in China and several challenges in clinical practice. More targeted interventions are needed to promote the use of BIC/FTC/TAF and DTG/3TC, enhance the accessibility, and ultimately improve health outcomes for PLWH.

OBJECTIVES:Recent years have witnessed unprecedented strides in comprehending non-CD4 regulatory T cells (Tregs), such as CD8 + Tregs and double-negative T cells (DNT cells), and their role in sustaining immune tolerance and restricting immune activation. This study investigates the role of Foxp3 + CD8 + T cells during HIV infection and assess the markers associated with CD4 + Tregs. DESIGN:This study was designed as a cross-sectional cohort study, comprising 21 age-matched healthy controls, 122 treatment-naive participants, and 60 people with HIV (PWH) receiving successful treatment (antiretroviral therapies, ARTs). METHODS:The frequency of Foxp3 + CD8 + T cells was assessed alongside CD4 + Treg-associated markers and plasma inflammatory factor levels. RESULTS:Foxp3 + CD8 + T cells were enriched in PWH with CD4 + T cell count less than 350 cells/μl and persisted after ART. Moreover, the Foxp3 + CD8 + T cells were correlated with CD4 + T cell count, CD4/CD8 ratio, and the parameters of activation and systematic inflammation in PWH. Moreover, Foxp3 + CD8 + T cells expressed different levels of Tregs related markers compared to CD4 + Tregs and Foxp3 + DNT cells. CONCLUSION:The Foxp3 + CD8 + T cells are associated with HIV disease progression and employ distinct mechanisms to exert their functions.

BACKGROUND:Despite antiretroviral therapy (ART), 10-40 % of people living with HIV (PLWH) fail to normalize CD4+ T cells, known as immune non-responders (INR), associated with poor clinical outcomes. Due to the complex pathogenesis and the absence of effective treatments, early prediction and intervention of INR are critical. With the rapid advancements in artificial intelligence, particularly in machine learning (ML), developing an interpretable ML model to identify individuals at high risk of INR can facilitate personalized treatment strategies and improve clinical management. METHODS:This retrospective study was conducted from a long-term multicenter cohort involving 30938 PLWH attending three hospitals from January 2003 to December 2023. Seven ML algorithms were employed to construct prediction models. The area under the receiver operating characteristic curve (AUC), precision-recall curves, calibration plots, clinical impact curves, and decision curve analysis were used to evaluate and identify the optimal model. We evaluated the final model using internal cross-validation and validated it in an external cohort. The Python-based Streamlit framework was applied to develop a web platform. RESULTS:11287 PLWH, including 1325 (11.74 %) INR, were analyzed in the derivation cohort. Twenty baseline clinical indicators of PLWH were used to construct ML models. After feature reduction and comparative evaluation, the 9-feature RF model demonstrated strong discrimination (AUC = 0.864), superior calibration, and favorable clinical utility, outperforming the traditional model (AUC = 0.856) and other models. The model performance was also confirmed in internal validation (mean AUC = 0.884 ± 0.003) and the external validation (AUC = 0.855). CONCLUSIONS:In this study, an interpretable ML model with nine baseline clinical indicators was constructed for early INR prediction in ART-naïve PLWH and was incorporated into a convenient web platform to facilitate individualized treatment and management.

Human immunodeficiency virus type 1 (HIV-1) infection is associated with over-activation, which contributes to disease progression. Platelet-leukocyte aggregates play a critical role in HIV-1 infection. However, research on the characteristics of platelet-natural killer (NK) cell aggregates in HIV-infected individuals still has certain limitations. Platelet-NK cell aggregates in the peripheral blood of participants were detected by flow cytometry and confirmed by imaging flow cytometry. Platelet activation was evaluated by CD62P expression. The expression of various activating and inhibitory receptors, markers of apoptosis, lipid droplets, interferon-gamma (IFN-γ), Granzyme B, and Perforin in platelet-NK cell aggregates were assessed. The signaling lymphocyte activating molecule (SLAM) family receptors in both platelets and NK cells and the levels of phosphorylation signals in NK cells were respectively measured through flow cytometry. In this study, we observed an increase in platelet-NK cell aggregates that were negatively correlated with CD4 count, a prognostic marker for HIV-1 disease progression. Furthermore, platelet activation was inversely associated with both HIV-1 disease progression and the platelet-NK cell aggregates. However, antiretroviral therapy (ART) couldn’t restore the levels of these aggregates or platelet activation. Compared to platelet-free NK cells, platelet-NK cell aggregates exhibited over-activation (CD69) and exhaustion phenotypes (CD39, LAG-3, PD-1), increased levels of apoptosis (Annexin V and CD95) and lipid droplets (Bodipy 493/503 and LipidTOX). Furthermore, NK cells' cytokine secretion (IFN-γ) and cytotoxic function (Granzyme B and Perforin) within the aggregates were declined. Screening results of SLAM receptors in NK cells and platelets suggested that platelets may transmit signals to NK cells via SLAMF5. Moreover, elevated levels of p-Fyn, p-PLC-γ2, p-SHP-1, and p-SHP-2 denoted disturbances in the downstream signals of the SLAM family within platelet-NK cell aggregates. Our study indicates that platelet-NK cell aggregates exhibit characteristics of over-activation and dysfunction during HIV-1 infection. Hyperactivated platelets and the formation of platelet-NK cell aggregates contribute to the HIV-1 disease progression and the inflammation of the immune system. These findings may implicate potential targets of overactivated platelets for HIV-1 disease progression.

With the advancement of combination antiretroviral therapy (cART), the global number of new human immunodeficiency virus (HIV) infections and HIV-related mortality has significantly declined. However, the high proportion of "late presentation" (defined as presenting to care with a low CD4 cell count or AIDS-defining events) among HIV-infected individuals remains a significant challenge in HIV prevention and treatment. HIV late presentation is associated with increased clinical risk, complex management, and higher risk of transmission, and represents a significant barrier to achieving the "95-95-95" targets and ending the HIV epidemic. Currently, both nationally and internationally, there is a lack of specific clinical guidelines for this population. Therefore, the China Association for Promotion of Health Science and Technology convened experts in the field to discuss the definition, clinical characteristics, risks, and cART of late presenters based on the latest research evidence and clinical practices both domestically and internationally. Specific recommendations were formulated to guide healthcare professionals in their clinical practice.