Background The extended survival of people living with HIV (PLWH) has shifted cancer burdens toward urological malignancies. PLWH exhibit unique clinical patterns, including younger age at diagnosis for renal cell carcinoma and more advanced stage at manifestations for prostate and bladder cancers, which are compounded by health care access inequities and human immunodeficiency virus (HIV)-specific mechanisms such as chronic immunosuppression. Methods A systematic search was conducted across five databases (Web of Science, PubMed, Cochrane Library, Embase, and Scopus) up to 1 July, 2025. Random-effects models were used to pool hazard ratios (HRs) and adjusted hazard ratios (aHRs). Publication bias was assessed using Egger's test, and sensitivity analyses were performed. Results Nine studies with 6,615,444 participants were included. The risk factors for mortality such as kidney cancer (aHR = 1.74; 95% CI: 1.11–2.75), prostate cancer (HR = 1.77; 95% CI: 1.60–1.96; aHR = 2.27; 95% CI: 1.77–2.90), and bladder cancer (aHR = 4.29; 95% CI: 1.08–17.03) were significantly higher for PLWH. The pooled unadjusted HR for kidney cancer was 1.66 (95% CI: 0.83–3.00) ,which did not reach statistical significance. Subgroup analyses for prostate cancer confirmed a consistent increase in mortality risk across different mortality types and follow-up durations. Conclusion HIV infection is significantly associated with increased mortality among patients with prostate cancer. For kidney cancer, limited data suggest an adverse prognostic role of HIV. For bladder cancer, the evidence remains preliminary but highlights the urgent need for dedicated investigations. These findings highlight the need to integrate urological cancer screening and tailored management into long-term HIV care. Future multicenter studies will be essential to strengthen the evidence, particularly for kidney and bladder cancers, and to clarify the roles of HIV-specific factors, tumor biology, and social determinants of health in optimizing precision medicine for this population.

Antiretroviral therapy (ART) effectively suppresses HIV-1 replication, yet T cell dysfunction persists in ART-suppressed people living with HIV-1 (PLWH). While mammalian target of rapamycin (mTOR) signaling drives T cell dysregulation, the role of DNA damage-inducible transcript 4 (DDIT4), a stress-induced mTOR inhibitor, in HIV-1 infection remains undefined. In this study, we aimed to investigate the expression of DDIT4 in immune cells, and clarify its associations with T cell dysfunction in ART-suppressed PLWH. We enrolled 24 ART-suppressed PLWH and 16 people living without HIV (PWoH). DDIT4 mRNA expression in peripheral blood mononuclear cells (PBMCs) was quantified by RT-qPCR. Flow cytometry was employed to assess DDIT4 protein expression together with T cell activation, exhaustion, and senescence markers. DDIT4 transcriptional expression was significantly elevated in ART-suppressed PLWH and positively correlated with hemoglobin levels (r = 0.524, P = 0.010). Notably, DDIT4 was markedly upregulated in gammadelta T cells which displayed memory phenotypes with increased CD38, HLA-DR, TIGIT, and CD57 expression, but diminished CD28 expression. Furthermore, the frequency of DDIT4⁺gammadelta T cells was correlated positively with the frequencies of CD28−CD57+gammadelta T cells, but inversely with CD4⁺ T cell counts, total lymphocytes, and monocytes. During HIV-1 infection, DDIT4 may act as a stress-responsive checkpoint, inducing gammadelta T cell exhaustion and senescence in ART-suppressed PLWH. These findings highlight the potential of DDIT4 as a therapeutic target to restore gammadelta T cells competence and offer novel insights into ART-refractory immune dysfunction.

Abstract Immune non-responders (INRs), a subset of people living with HIV (PLWH), fail to achieve full immune reconstitution and remain at increased risk of morbidity, mortality, and non-AIDS-related illnesses. As the mechanisms underlying this impaired immune recovery remain poorly understood, we performed single-cell multi-omics profiling on peripheral blood mononuclear cells from 43 INRs, 47 immune responders and 53 healthy donors. Our dataset comprises 2,744,009 transcriptomes and 1,226,658 chromatin-accessibility profiles across 58 identified immune cell types. INRs exhibited markedly elevated inflammatory signaling, increased apoptotic activity, and dysregulation of immune-activating ligand-receptor interactions. Additionally, we identified 2,996 interaction cis -eGenes and 5,938 cis -caPeaks, and validated key cell type-specific cis -xQTL effects associated with immune reconstitution failure. Furthermore, we identified 3,551 sc-eQTLs and 872 cell-state interaction eQTLs (ieQTLs) in CD4 + T cells. A genotype-specific upregulation of OAS3 in INRs, likely regulated by STAT1, was identified based on these results. We developed scPRISM (single cell Predictive Reconstitution Immune Status Model), a multi-modal framework that integrates scRNA-seq and scATAC-seq data to perform the dual tasks of differentiating disease states and predicting gene expression from chromatin accessibility, thereby deciphering the cell type-specific cis -regulatory basis of the disease. Our study delineates the transcriptional and epigenomic landscape of immune dysregulation in INRs and provides new genetic insights into HIV-associated immune reconstitution failure. These findings offer a foundation for developing biomarkers and precision therapies to restore immune function in PLWH.

A substantial proportion of mpox cases occur in people with HIV, but how HIV coinfection and immune status affect clinical outcomes remains unclear. We systematically searched major databases up to March 2025 for observational studies comparing mpox patients with and without HIV coinfection. Pooled effect sizes were calculated using random-effects models. Risk ratios (RRs) or standardized mean differences (SMDs) with 95% confidence intervals were used for dichotomous or continuous outcomes. Post hoc subgroup analyses explored differences by economic development, viral suppression, and advanced HIV disease (AHD) proportion. Among 15,522 patients from 29 studies, 52.43% had HIV. HIV coinfection was associated with higher hospitalization [RR = 1.50, 95% CI (1.17, 1.93)] and mortality [RR = 4.54, 95% CI (2.11, 9.77)]. Coinfected patients had more syphilis, HBV, and HCV coinfections, and higher rates of fever, proctitis, malaise, rectal irritation syndrome, diarrhoea, skin and soft tissue infections, and pneumonia. Blood tests showed lower albumin, calcium, and haemoglobin, and higher CK-MB. Perianal lesions were more common with HIV. HIV coinfection is linked to greater clinical severity, mortality, and STI coinfections. Exploratory analyses suggest poor viral suppression may drive adverse outcomes, and lesion severity relates to immune status. All subgroup findings are post hoc and hypothesis-generating, limited by aggregate data. Intensified monitoring and supportive care, vaccination, and optimized ART initiation are crucial for this population.

CD39 exerts an inhibitory effect on tumour progression by impairing the cytotoxic capacity of natural killer (NK) cells against cancer cells. However, the impact of CD39 expression on the non-cytolytic functions of NK cells in treatment-naïve human immunodeficiency virus type 1 (HIV-1)-infected individuals remains poorly understood. In this study, thirty-four individuals with acute HIV-1 infection (AHI), thirty-eight with chronic HIV-1 infection (CHI), and twenty-four HIV-1-negative healthy controls (HC) were enrolled to explore the role of CD39 expression on NK cells in HIV-1 suppression at different infection stages. Flow cytometry was employed to analyze the immune phenotype and functional characteristics of NK cells. We found that CD39 expression on NK cells was significantly upregulated following HIV-1 infection, and its positive rate was positively associated with HIV-1 viral load in both AHI and CHI individuals. Compared with CD39- NK cells, CD39+ NK cells exhibited reduced activation; in AHI individuals, the activation level of CD39+ NK cells was positively associated with HIV-1 viral load but inversely correlated with CD4+ T-cell counts. In CHI individuals, the interleukin-10 (IL-10)-producing capacity of total NK cells, CD39+ NK cells, and CD39- NK cells was enhanced and positively correlated with HIV-1 viral load. Additionally, across the AHI and CHI groups, the overall IL-10-secreting ability of NK cells was positively correlated with the frequency of CD39+ NK cells. In both AHI and CHI individuals, CD39+ NK cells showed lower T-cell immunoglobulin and ITIM domain (TIGIT) expression than CD39- NK cells, while the CD39+TIGIT+ NK cell subset displayed significantly stronger IL-10-secreting capacity. POM-1, an inhibitor of CD39 ectonucleotidase activity, could enhance IL-10 secretion by NK cells in both HIV-1-infected individuals and the majority of healthy controls, but attenuate interferon-γ (IFN-γ) secretion by NK cells in HIV-1-infected individuals. In contrast, the CD39-blocking antibody A1 reduced IFN-γ secretion without affecting IL-10 secretion by NK cells in both HIV-1-infected individuals and healthy controls. Our findings reveal a novel CD39+ NK cell-associated mechanism that contributes to ineffective HIV-1 control, and suggest that CD39, alone or combined with TIGIT, may serve as a promising target to restore antiviral NK cell function in treatment-naïve individuals living with HIV-1.

BackgroundHIV remains globally prevalent, and the long-term complications experienced by people living with HIV (PLWH) have increased interest in the functional heterogeneity of extracellular vesicle (EV) subpopulations. Defining these EV subsets may help clarify HIV-associated immune dysregulation and inform future diagnostic and therapeutic strategies.MethodsPlasma samples were obtained from three PLWH (HIV+ group) and three healthy controls (HC group). Single-EV surface membrane proteins were profiled using the proximity barcoding assay (PBA), and EV subpopulations were identified by FlowSOM clustering with t-SNE visualization. Functional enrichment analysis, protein-protein interaction (PPI) network analysis, and database-based annotation were used to infer putative subpopulation functions and cellular origins. Differentially expressed EV proteins (DEPs) were screened using limma, and ligand-receptor interaction networks were constructed with CellPhoneDB and cross-referenced with publicly available single-cell RNA sequencing data.ResultsHIV infection did not appear to alter overall EV abundance but was associated with selective remodeling of EV heterogeneity and expansion of distinct EV subpopulations. CD31+ EVs (cluster 2), inferred to be endothelial-derived, were markedly enriched in PLWH. Ligand-receptor analysis suggested that CD31+ EVs may communicate with CD16+ monocytes through F11R-ITGAL/ITGB2 and with plasmablasts through CD31-CD38 interactions; these interactions were associated with inflammatory, leukocyte transendothelial migration, and metabolic pathways. In addition, HIV-enriched B2M+ EVs (clusters 3) and MUC16+ EVs (clusters 9) showed predicted interactions with CD4+ T cells and with CD8+ effector memory T and NK cells, respectively, suggesting potential effects on reservoir-related and cytotoxicity-related programs.ConclusionsThese exploratory findings suggest that EV heterogeneity may encode cell-type-specific immune regulatory information in HIV infection and highlight CD31+ EVs as a candidate EV subset associated with HIV-related immune dysregulation. Larger cohorts and functional validation are required before these EV populations can be considered therapeutic targets for HIV cure strategies.

Antiretroviral therapy (ART) has significantly extended the life expectancy of people with HIV (PWH), rendering population ageing and immunosenescence prominent clinical priorities. T-cell senescence is linked to mitochondrial dysfunction and drives age-related immune remodelling, yet how HIV infection and ageing jointly shape CD4+ and CD8+ T-cell immunophenotypes and mitochondrial remodelling remains unclear. This cross-sectional study included 61 PWH on suppressive ART for ≥ 12 months and 61 age- and sex-matched HIV-negative men who have sex with men, stratified into younger (≤ 35 years) and older (≥ 50 years) groups. Multiparameter flow cytometry was used to profile CD4+ and CD8+ T-cell differentiation, stemness, activation/exhaustion, and metabolic phenotypes, together with mitochondrial mass and membrane potential. We found that ageing and HIV infection were associated with T-cell remodelling, characterized by expanded late-differentiated phenotypes and reduced stem-like, homeostatic and costimulatory CD4+ and CD8+ T-cell subsets, as indicated by upregulated CD57 and CX3CR1 and downregulated CD45RA+CD31+, FOXO1, and CD28. Notably, younger PWH had an ageing-like CD4+ T-cell profile, with higher CD57, CX3CR1 and TIGIT expression than younger HIV-negative individuals. In contrast, HIV-related CD8+ T-cell perturbations (KLRG1, CXCR3, NKG2C and CD95) were more pronounced in older PWH. PWH exhibited increased mitochondrial mass and membrane potential in both total and senescent-like CD4+ and CD8+ T cells, particularly in CD8+ T cells from older PWH. In CD4+ T cells, KLRG1 and CX3CR1 expression correlated positively with age, and inversely with CD4+ T-cell counts and CD4/CD8 ratio. By contrast, FOXO1 expression in CD8+ T cells was inversely associated with age, late-differentiation markers, and ART duration in PWH. Overall, age is a major driver of T-cell immunosenescence, and HIV infection modulates and exacerbates these alterations. Mitochondrial stress, FOXO1 downregulation and immune network remodelling support a multifaceted model of HIV-associated immune ageing that may contribute to heterogeneous immune reconstitution in PWH, highlighting potential targets to mitigate immune ageing.

Chikungunya virus (CHIKV) is a globally emerging arthropod-borne virus causing widespread febrile outbreaks, with its endemic regions showing extensive geographical overlap with human immunodeficiency virus (HIV). Approximately 71% of people living with HIV (PLWH) reside in CHIKV high-risk areas globally, while the clinical features and underlying immunological interplay of CHIKV-HIV co-infection have not been systematically synthesized. This review integrates current evidence on CHIKV host immune responses, alongside the epidemiological characteristics, clinical manifestations, and immunopathological mechanisms of CHIKV infection in PLWH, to deliver integrated clinical and immunological insights into co-infection. Available data indicate that PLWH on suppressive antiretroviral therapy (ART) generally present with milder CHIKV disease, with potential mechanisms involving HIV-induced immune system alterations and direct antiviral activity of ART. This review provides an evidence-based framework for clinical management and public health prevention strategies for this vulnerable population.

Background:Large-scale, multicenter, long-term real-world studies investigating the associations between bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide fumarate (TAF) (B/F/TAF) versus dolutegravir (DTG)-based regimens and virologic, immunologic, metabolic outcomes, and mortality in people with HIV (PWH) are scarce. Methods:Our study incorporates anonymized clinical records of PWH who newly started antiretroviral therapy (ART) in 19 centers across China. We retrieved data for PWH who initiated ART between January 1, 2020 and December 31, 2023. Inclusion criteria: baseline age ≥18 years, ART naïve, and initiated one of the following regimens: B/F/TAF, DTG+ tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) (DTG+TDF+3TC), or DTG/3TC. Poisson regression models with time offset and robust variance were used to estimate adjusted incidence rate ratios (aIRRs) for virologic suppression (HIV RNA <50 copies/mL), all-cause mortality, AIDS-related mortality, and non-AIDS-related mortality, adjusting for key demographic and clinical variables. Linear mixed models with interaction terms (time-versus-treatment group) and restricted cubic splines with one knot at 1 year after ART initiation were used to evaluate differences in CD4 counts, CD4/CD8 ratios, body weight, blood glucose, triglycerides, and total cholesterol changes among treatment groups. Findings:13,895 Individuals (median age: 38 years [IQR 29-53], 86.6% male) were included. Compared to the B/F/TAF regimen, individuals initiating DTG+TDF+3TC were associated with an 8% increase in virologic suppression incidence (aIRRs 1.08, 95% CI 1.00-1.17), while those on DTG/3TC observed no significant differences. CD4 count and CD4/CD8 ratio were significantly smaller in the DTG/3TC group during the first year and over 2-4 years compared to B/F/TAF. DTG+TDF+3TC group were associated with significantly lower triglycerides (-0.41 mmol/L, 95% CI -0.48 to -0.35 in the first year; -0.06 mmol/L, 95% CI -0.12 to 0 over 2-4 years) and total cholesterol (-0.57 mmol/L, 95% CI -0.62 to -0.52 in the first year; -0.07 mmol/L, 95% CI -0.12 to -0.01 over 2-4 years) and less weight gain (-4.13 kg, 95% CI -4.73 to -3.54 in the first year; -1.39 kg, 95% CI -1.98 to -0.81 over 2-4 years) compared to B/F/TAF. All-cause mortality did not differ significantly between B/F/TAF and DTG+TDF+3TC users, but individuals who started DTG/3TC were observed to have a 37% higher all-cause mortality rate (1.37, 1.06-1.77) compared to B/F/TAF. Non-AIDS-related mortality was associated with 53% higher in DTG/3TC users (1.53, 1.15-2.03) compared to B/F/TAF. Among individuals with baseline weight >77 kg, each 10% increase in body weight at one year on ART was associated with 23% higher all-cause mortality and 38% higher non-AIDS-related mortality. Interpretation:PWH initiating B/F/TAF in China were observed to have comparable virologic suppression compared to those starting DTG/3TC and DTG+TDF+3TC, although differences were observed in immunologic improvement, mortality rates, and metabolic changes. Subsequent weight gain after ART initiation merits heightened attention among individuals with higher baseline body weight. Funding:National Key Technologies R&D Program of China.

BACKGROUND:Corrected QT (QTc) interval prolongation elevates fatal arrhythmia risk in people living with HIV (PLWH). Ainuovirine (ANV), a novel non-nucleoside reverse transcriptase inhibitor, demonstrates a favorable preclinical safety profile. This study evaluated ANV's effects on QTc interval and creatine kinase MB (CK-MB) levels in humans. METHODS:A pooled analysis was conducted using data from four phase 1 clinical studies: a single ascending dose (SAD), a food effect (FED), a multiple ascending dose (MAD), and a drug-drug interaction (DDI) study with lamivudine/tenofovir disoproxil fumarate (3TC/TDF). The analysis included healthy adults and treatment-naïve PLWH receiving ANV monotherapy or combination therapy. Concentration-QTc (C-QTc) modeling was performed using linear regression and linear mixed-effects (LME) models. The relationship between drug exposure (ANV, 3TC, TDF) and serum CK-MB levels was also assessed. RESULTS:Analysis of 85 participants with 838 time-matched C-QTc pairs revealed statistically insignificant negative slopes for ANV C-QTc relationships across all models. This indicates no significant ANV effect on QTc prolongation, consistent from subtherapeutic to supratherapeutic doses (75-300 mg). Bootstrapping validated model precision and reliability. ANV and lamivudine exposures showed no correlation with CK-MB elevation, while tenofovir disoproxil fumarate exposure demonstrated a positive correlation that remained clinically insignificant. CONCLUSIONS:ANV exhibits no statistically significant or clinically meaningful effect on QTc interval prolongation in healthy adults and treatment-naïve PLWH, even at supratherapeutic doses. CK-MB elevations were associated with tenofovir disoproxil fumarate exposure rather than ANV or lamivudine. These findings support the favorable cardiac safety profile of ANV-based regimens.

BackgroundGlobal and Chinese efforts still face significant gaps in achieving the first 95% of the “95-95-95” target, with persistently high and rising rates of late HIV diagnosis. This study evaluates RNA/DNA quantification, RNA qualitative, and ELISA assays to optimize HIV testing strategies.MethodsA prospective cross-sectional study evaluated 215 first-time HIV testers from June 2024 to May 2025. Using clinical diagnosis as the reference standard, we assessed four methods' sensitivity, specificity, and subgroup performance, with tandem testing strategies simulation for optimal detection.ResultsDNA quantitative detection demonstrated optimal performance with 100% sensitivity and specificity. RNA quantitative assay showed 99.02% sensitivity and 100% specificity, while ELISA achieved 99.02% sensitivity and 98.23% specificity. RNA qualitative testing exhibited 99.02% sensitivity but lower specificity (75.22%). ROC revealed superior diagnostic performance for DNA quantitative (AUC = 1.000) and RNA quantitative (AUC = 0.995) compared to RNA qualitative (AUC = 0.871). All methods maintained consistent sensitivity across CD4+ T cell levels. Simulation of tandem strategies identified ELISA combined with DNA quantitative testing as optimal (net sensitivity: 99.02%, net specificity: 100%, total tests: 318). For 18 WB-indeterminate samples, DNA/RNA quantitative methods achieved 100% diagnostic accuracy, outperforming RNA qualitative (94.44%) and ELISA (83.33%).ConclusionDNA quantitative detection shows high diagnostic value in initial HIV testing, overcoming challenges from undisclosed ART-induced RNA suppression and resolving WB-indeterminate misclassifications to reduce late diagnosis risks. This study supports Nucleic acid tests into diagnostic algorithms and validates the superior performance of ELISA screening followed by DNA confirmation, offering actionable strategies to shorten diagnostic delays and advance national AIDS control objectives.

Background:The extended survival of people living with human immunodeficiency virus (HIV) (PLWH) has shifted cancer burdens toward urological malignancies. PLWH exhibit unique clinical patterns, including a younger age at diagnosis for renal cell carcinoma and more advanced stage at presentation of prostate and bladder cancers, which are compounded by inequities in health care access and HIV-specific mechanisms such as chronic immunosuppression. Methods:A systematic search was conducted across five databases (Web of Science, PubMed, Cochrane Library, Embase, and Scopus) up to 1 July, 2025. Random-effects models were used to pool hazard ratios (HRs) and adjusted hazard ratios (aHRs). Publication bias was assessed using Egger's test, and sensitivity analyses were performed. Results:Nine studies with 6,615,444 participants were included. The risk factors for mortality such as kidney cancer (aHR = 1.74; 95% confidence interval [CI]: 1.11-2.75), prostate cancer (HR = 1.77; 95% CI: 1.60-1.96; aHR = 2.27; 95% CI: 1.77-2.90), and bladder cancer (aHR = 4.29; 95% CI: 1.08-17.03) were significantly higher for PLWH. The pooled unadjusted HR for kidney cancer was 1.66 (95% CI: 0.83-3.30), which did not reach statistical significance. Subgroup analyses for prostate cancer confirmed a consistent increase in mortality risk across different mortality types and follow-up durations. Conclusion:HIV infection is significantly associated with increased mortality among patients with prostate cancer. For kidney cancer, limited data suggest an adverse prognostic role of HIV. For bladder cancer, the evidence remains preliminary but highlights the urgent need for dedicated investigations. These findings highlight the need to integrate urological cancer screening and tailored management into long-term HIV care. Future multicenter studies will be essential to strengthen the evidence, particularly for kidney and bladder cancers, and to clarify the roles of HIV-specific factors, tumor biology, and social determinants of health in optimizing precision medicine for this population.

ObjectiveBoth B-cell- and T-cell-mediated immunity are crucial for the effective clearance of viral infection, but little is known about the dynamic characteristics of SARS-CoV-2-specific B-cell and T-cell responses in people living with HIV (PLWH) after a full course of inactivated SARS-CoV-2 vaccination.MethodsIn this study, fifty people living with HIV (PLWH) and thirty healthy controls (HCs) were enrolled to assess B-cell and T-cell responses at the day before the vaccination (T0), two weeks after the first dose (T1), two months after the first dose (T2), the day of the third dose (T3), one month after the third dose (T4), three months after the third dose (T5) and 12 months (T6) after the third dose.ResultsSARS-CoV-2-specific B-cell and T-cell responses were induced in people living with HIV (PLWH), and these responses lasted at least one year after the third vaccine dose. However, the peak frequencies of Spike-specific B-cell and T-cell responses in PLWH were lower than those in HIV-negative controls. In addition, the expansion of activated B cells, memory B cells and plasma cells after primary vaccination was observed, but the percentages of these cells were decreased at T6 and were comparable to those at T0. Additionally, the percentages of activated T cells, exhausted T cells and SARS-CoV-2-specific T cells with enhanced functional activity were increased following the administration of inactivated SARS-CoV-2 vaccine. In addition, PLWH had lower percentages of plasma cells, RBD-specific B cells, circulating Tfh (cTfh) cells and CD38+ cTfh cells, and the percentages of the latter two types of cells were positively correlated with the titer of neutralizing antibodies, indicating these differences may account for the weaker immune responses induced in PLWH.ConclusionThese data suggest that specific B-cell and T-cell responses could be sustained for at least one year after receiving the third vaccination. Our findings emphasize that the weak SARS-CoV-2-specific B-cell and T-cell responses induced in PLWH have implications for clinical decision-making and public health policy for PLWH with respect to SARS-CoV-2 infection.

Prior research indicated low genotypic resistance testing (GRT) for human immunodeficiency virus (HIV) utilization in China due to partial cost coverage under national antiretroviral therapy policies, limited testing accessibility, and financial barriers. Temporal and spatial data on GRT trends were also scarce. We analyzed GRT patterns among 6,895 untreated individuals at a tertiary hospital using Joinpoint regression, multivariable logistic modeling, and spatial analysis (GeoDa/SatScan). GRT rates showed a significant two-phase upward trend, increasing from 5.36 % in 2014 to 74.17 % in 2023, with an average annual percentage change of 31.30 % ( P < 0.001). Beijing residency (adjusted odds ratio [aOR] = 2.596, 95 % confidence interval [CI]: 2.307-2.921) and older age were associated with higher GRT uptake. Specifically, ages 35-44 years (aOR= 1.207, 95 % CI: 1.026-1.420), 45-54 years (aOR = 1.335, 95 % CI: 1.104-1.613), and ≥ 55 years (aOR= 1.424, 95 % CI: 1.126-1.802) had significantly higher odds of testing. Lower testing rates were observed in individuals with lower education attainment (high school or technical secondary: aOR = 0.827; junior high school: aOR = 0.835; primary school: aOR = 0.695), unknown sexually transmitted diseases (STDs) history (aOR = 0.415), and non-heterosexual transmission routes (homosexual: aOR = 0.834). Spatial analysis identified GRT clustering across Beijing until 2021, with two space-time clusters identified in 2019-2023 and 2018-2022. This study demonstrates substantial increase in GRT uptake achieving more balanced district-level distribution since 2021. Age, educational attainment, STDs history, and transmission route influence GRT utilization. Improving access, reducing costs, and implementing targeted interventions are critical for optimizing testing and guiding antiretroviral therapy decisions.

Elite controllers (ECs) and post-treatment controllers (PTCs) represent important models for achieving a functional cure for HIV. This review synthesizes findings from immunological, genetic, and virological studies to compare the mechanisms underlying HIV suppression in ECs and PTCs. Although ECs maintain viral control without antiretroviral therapy (ART), PTCs achieve suppression following ART discontinuation. Both groups rely on adaptive and innate immunity, host genetic factors, and characteristics of the HIV reservoir; however, they exhibit distinct immune responses and genetic profiles. These differences provide insights into strategies for sustained ART-free remission. Understanding the shared and unique mechanisms in ECs and PTCs can inform the development of novel therapeutic approaches, including immune-based therapies and genome editing, to achieve a functional cure for HIV-1.

Abstract Background Ainuovirine (ANV) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) for treatment of HIV-1 infection. This study aimed to evaluate the safety, pharmacokinetics, and antiviral activity of short-term ANV monotherapy in antiretroviral treatment-naive adults with HIV-1.Table 1.Summary statistics of pharmacokinetic parameters of ainuovirine after single-dose and multi-doses in treatment-naïve HIV-infected adults. Data are expressed in median ± standard deviation (min, max); AUC0–t, area under the plasma concentration-time curve from time zero to time of the last quantifiable concentration; AUC0-t,ss, AUC0-t at steady state; AUC0-∞,ss, AUC from time zero to infinity at steady state; AUC0-τ, AUC at steady state; AUC_%Extrap, percentage of extrapolated AUC; Cmax, maximum plasma concentration; Cmax,ss, Cmax at steady state; Cmin,ss, minimum plasma concentration at steady state; Cav,ss, average steady state concentration; CLss/F, apparent clearance at steady state; DF, degree of fluctuation; MRT0-∞, mean retention time from time zero to infinity; Ra, accumulation ratio; Tmax, time to maximum plasma concentration; Tmax,ss, Tmax at steady state; T1/2z, plasma terminal half-life; Vz/F, apparent volume of distribution; λz, elimination rate constant. Methods A single-center, open-label, dose-ranging study was conducted among 28 treatment-naive adults with HIV-1. Participants received ainuovirine monotherapy, 75, 150, or 300 mg, once daily, for 10 days.Figure 1.Mean change from baseline in HIV RNA.Data are expressed in median±standard deviation. Results Baseline characteristics were similar across dose cohorts (75 mg, n=8; 150 mg, n=10; 300 mg, n=10). Across all dose cohorts, all adverse events were rated as mild to moderate in severity. No serious adverse event was reported. Pharmacokinetic parameters are shown in Table 1. ANV was readily absorbed, with the maximum concentration achieved at a median time of approximately 2-3 h after dosing. The ANV exposure (AUC and Cmax) increased slightly greater than the dose proportionality after single dose (day 1). Plasma ANV concentration reached the steady state at day 10 of dosing. Saturated Cmax,ss, AUCmax,ss, and C24h,ss were observed at 150 and 300 mg on day 10 after repeated dosing. Mean changes in HIV RNA from baseline (log10 copies/mL [90%CI]) were -1.73 [-1.90, -1.57], -1.72 [-1.87, -1.57], and -1.66 [-1.80, -1.51], respectively, on day 11 (Figure 1). Conclusion ANV demonstrated favorable safety and pharmacokinetics, and potent antiviral activity in treatment-naive adults with HIV-1.An once-daily dosing regimen of 150 mg was recommended for subsequent confirmatory efficacy trial. Disclosures Li Zhang, M.S., Jiangsu Aidea Pharmaceutical Co., Ltd.: Honoraria Xinming Yun, PhD, Jiangsu Aidea Pharmaceutical Co., Ltd.: Honoraria Hong Qin, MD, PhD, Jiangsu Aidea Pharmaceutical Co., Ltd: Honoraria

>In 2014, the Joint United Nations Programme on HIV/AIDS(UNAIDS) first proposed the vision of “ending AIDS by 2030”, aiming to reduce new HIV infections and AIDS-related deaths to minimal levels while eliminating all forms of HIVrelated stigma and discrimination(Kirby, 2018). In 2021, the United Nations General Assembly adopted a new global political declaration on AIDS, which committed countries to achieving the “95-95-95” target by 2030.

To assess the prognostic value of baseline HIV-1 DNA levels, a meta-analysis was conducted according to the PROSPERO protocol (CRD42024619050) based on data from studies published until March 4, 2025. Relevant studies were retrieved from the Web of Science, PubMed, Cochrane Library, Embase, and Scopus databases. Effect sizes (correlation coefficients, odds ratios [ORs], hazard ratios [HRs], and adjusted hazard ratios [aHRs]) were calculated using R software, with subgroup analyses and assessment of publication bias and sensitivity. Seventeen studies involving 4789 participants were included. The combined correlation coefficient between pre - and on-ART HIV-1 DNA levels was 0.71 (95% confidence Interval (CI): 0.63-0.78). Baseline DNA levels were significantly associated with viral rebound after viral suppression (combined OR = 1.74, 95% CI: 1.25-2.41; HR = 2.01, 95% CI: 1.58-2.56; aHR = 2.26, 95% CI: 1.75-2.92). For clinical progression, the combined HR and aHR for continuous baseline DNA were 3.66 (95% CI: 2.87-4.66) and 2.44 (95% CI: 1.87-3.20), respectively, with high baseline DNA levels associated with an increased risk of clinical progression (HR = 2.58, 95% CI: 1.96-3.39; aHR = 1.90, 95% CI: 1.41-2.55). For mortality, the HR and aHR were 3.22 (95% CI: 1.96-5.29) and 2.15 (95% CI: 1.21-3.84) respectively, with high baseline DNA levels associated with an increased risk of death (HR = 3.54, 95% CI: 1.39-9.00; aHR = 2.86, 95% CI: 1.01-8.08). Higher pre-ART HIV-1 DNA levels are associated with increased risks of viral rebound, clinical progression, and mortality. These results suggest that baseline HIV-1 DNA represents a potentially valuable supplementary biomarker for monitoring disease progression and treatment response.