BACKGROUND:Tenofovir disoproxil fumarate (TDF) carries bone and renal toxicity risks. Data are limited on Chinese people living with HIV (PLWH) switching from TDF-based regimens to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and non-BIC/FTC/TAF. RESEARCH DESIGN AND METHODS:This retrospective cohort study enrolled virologically-suppressed PLWH receiving TDF (>48 weeks) at PUMCH (2014-2025). We analyzed efficacy/safety at 96 weeks post-switch to BIC/FTC/TAF or non-BIC/FTC/TAF. Primary endpoints: viral suppression, immune recovery, and safety [bone mineral density(BMD)/eGFR/weight/serum lipids], assessed from 48 weeks pre-switch to 96 weeks post-switch. RESULTS:After screening, 169 of 1,592 PLWH were enrolled (mean age 41 years; 89.3% male; mean TDF duration 67.8 month): 111 switched to BIC/FTC/TAF, 58 to non-BIC/FTC/TAF (25 dolutegravir-based). All BIC/FTC/TAF recipients maintained virologic suppression but one low-level viremia in non-BIC/FTC/TAF, CD4+ T-cell increased similarly (p > 0.05). Pre-switch (48-week on TDF) BMD decreased (spine/hip/femoral neck: -1.78%/-3.03%/-2.39%); At week 96 post-switch, BMD increased (BIC/FTC/TAF: +3.55%/+2.52%/+3.48%; non-BIC/FTC/TAF: +2.18%/+2.19%/+2.8%; p > 0.05). Pre-switch eGFR similarly decreased: -9 mL/min/1.73 m2, post-switch increased (BIC/FTC/TAF +3.6 vs non-BIC/FTC/TAF +5.1, p > 0.05). Pre-switch slight weight gain (+0.27 kg), post-switch: BIC/FTC/TAF (+1.59 kg), dolutegravir (DTG)-based (+3.54 kg), non-DTG/BIC (+0.95 kg). Serum lipids increased in all groups (p > 0.05). CONCLUSIONS:Switching from TDF to BIC/FTC/TAF or Non-BIC/FTC/TAF was associated with improved bone/renal safety with maintained efficacy in Chinese PLWH. But integrase strand transfer inhibitor(INSTI)-based regimens necessitate monitoring for weight and lipid changes. These findings warrant confirmation in larger studies.

Activating the type I interferon response in tumor cells and enhancing T cell-mediated anti-tumor immunity have broad clinical applications in tumor immunotherapy. However, the detailed mechanisms underlying the antitumor immune response and type I interferon response in nasopharyngeal carcinoma (NPC) remain unclear and require further elucidation. In this study, we identify CD38 in NPC cells as a key mediator impairing T cell antitumor immunity. Mechanistically, CD38 induces mitochondrial autophagy through PHB2, enhances the interaction between PHB2 and MAVS, leading to the degradation of MAVS protein, and inhibits the type I interferon response and CD8+T cell-mediated anti-tumor immunity. Importantly, CD38 promotes tumor progression and reduces the proportion of CD8+T cells and IFNγ+CD8+T cells in vivo via MAVS. In conclusion, these findings reveal previously unrecognized roles and mechanisms of CD38 in regulating anti-tumor T cell immunity, suggesting that inhibition of CD38 could initiate tumor-targeted immune responses, enhance anti-tumor immunity in patients, and provide new therapeutic strategies for NPC.

As a cell surface glycoprotein, CD90 plays a significant role in the initiation and progression of malignancies such as gastric cancer (GC) by influencing tumor cell proliferation, migration, and angiogenesis. However, its specific role in immune evasion in GC and its potential therapeutic value have not been fully explored. In this study, we report that CD90 is highly expressed in GC tissues and is positively correlated with macrophage immune infiltration. Furthermore, we demonstrate that CD90 can mediate immune evasion in GC by affecting the phagocytic function of tumor-associated macrophages (TAMs). Mechanistically, CD90 functions as a scaffold protein, inhibiting the interaction between IGF2BP2 and TRIM21. This inhibition stabilizes the expression of the m6A methylation reader protein IGF2BP2. Subsequently, IGF2BP2 enhances the mRNA stability of the immune checkpoint molecule CD47 in an m6A-dependent manner, leading to the activation of the CD47/SIRPα axis. Ultimately, by inhibiting the phagocytic function of TAMs, CD90 mediates immune evasion in GC. In summary, our work highlights the critical role of the CD90-IGF2BP2-CD47 axis in immune evasion in GC. This finding is expected to provide significant experimental evidence for elucidating the pathogenesis of GC and discovering potential molecular targets for clinical treatment.

Chemotherapy is one of the important means to improve the 5-year survival rate of nasopharyngeal carcinoma (NPC) patients, and commonly used chemotherapy drugs include cisplatin and gemcitabine. Previous studies have shown that chemotherapy can induce some tumor cells to exhibit a senescent phenotype, thereby altering the tumor microenvironment towards tumor immune suppression and tumor recurrence. However, the role and detailed mechanism of chemotherapy in the senescence of NPC cells are not yet clear, and further in-depth research is needed. This study focuses on the mechanism of cisplatin-induced cellular senescence, a major form of chemotherapy-induced senescence, in the progression of NPC. Our study found that cisplatin induces tumor cell senescence, upregulates EBI3 expression, and promotes abnormal secretion of IL-35 to mediate tumor immune escape. Specifically, senescent NPC cells release mtDNA due to mitochondrial damage, which in turn activates the cGAS-STING signaling pathway. Activation of this pathway induces the nuclear translocation of NF-κB p65, which directly binds to the EBI3 promoter and significantly upregulates EBI3 expression. Subsequently, EBI3 binds to the p35 subunit to form IL-35, which activates the JAK-STAT1 pathway of NK cells through IL-12Rβ2/GP130 receptors, inducing upregulation of the inhibitory receptor NKG2A and thereby weakening the anti-tumor function of NK cells. This study reveals for the first time a novel molecular mechanism by which cisplatin-induced senescent cells, a representative of chemotherapy-induced senescent cells, regulate NK cell anti-tumor function through the EBI3/IL-35 axis, and identifies EBI3 as a key molecular target involved in chemotherapy-induced senescence-mediated immune suppression in NPC, providing important experimental evidence for developing targeted immunotherapy strategies for NPC.

A‑Raf is a serine/threonine protein kinase that belongs to the RAF kinase family. A‑Raf serves key roles in various physiological and pathological processes, including cell cycle regulation, apoptosis, material transport and metabolism, embryonic development, bone mass maintenance and tumor progression. As research has advanced, the functional mechanisms of the A‑Raf gene have attracted increasing attention. To systematically summarize its biological functions, the present review focuses on the effects of A‑Raf on the cell cycle, apoptosis and cell proliferation, its influence on cellular material transport and metabolic processes, its role in organismal development and bone mass maintenance, its impact on tumor progression, the effects of genetic variations on A‑Raf function and the regulation of A‑Raf by upstream factors. The present review therefore aimed to provide a novel perspective for the comprehensive understanding of the function of A‑Raf.

BackgroundIncomplete immune reconstitution (INR) affects 9%–45% of ART-treated people living with HIV (PLWH) and is associated with increased morbidity and mortality. Chronic immune activation and inflammatory signaling, particularly via the IP-10/CXCL10 pathway, are central to its pathogenesis. Whether Tripterygium wilfordii Hook F (TwHF), an immunomodulatory agent with established anti-inflammatory properties, can improve CD4+ T-cell recovery in virologically suppressed PLWH with INR remains unclear.MethodsWe conducted a retrospective longitudinal cohort study at Peking Union Medical College Hospital. ART-treated, virologically suppressed PLWH with persistent CD4+ T-cell counts <350 cells/μL were enrolled and classified into a TwHF group (n = 32, 10 mg three times daily) or a matched control group (n = 31). Participants were followed at five predefined time points spanning 12 months pre-treatment through 12 months post-discontinuation. Peripheral blood immunophenotyping assessed CD4+ T-cell subsets (naïve and memory), CD4/CD8 ratio, and CD8+ T-cell activation markers. A cytokine substudy measured IP-10/CXCL10 and eotaxin in 20 TwHF-treated and 14 control participants using multiplex immunoassay. Linear mixed-effects models were used for longitudinal analysis.ResultsTwHF was associated with a significantly accelerated rate of CD4+ T-cell recovery compared with controls (group × time interaction coefficient 4.98, P < 0.001), with median counts of 254 vs. 222 cells/μL at 12 months (P = 0.011). This gain was attributable predominantly to memory CD4+ T-cell expansion (216 vs. 164 cells/μL, P < 0.001), while naïve CD4+ T-cell counts remained unchanged. The CD4/CD8 ratio improved more rapidly in the TwHF group (0.409 vs. 0.278 at month 12, P = 0.008). A clinically meaningful response (≥50 cells/μL/year) was achieved in 75.0% of TwHF-treated vs. 9.7% of controls. Within-person IP-10/CXCL10 levels declined significantly after TwHF treatment (median Δ −31.96 pg/mL, P = 0.017), particularly in good immunological responders. Immunological gains attenuated after treatment discontinuation, suggesting a treatment-dependent effect. Routine hematological and renal parameters remained within normal limits throughout follow-up, with no significant between-group differences. No serious adverse events were observed.ConclusionTwHF accelerates CD4+ T-cell reconstitution in virologically suppressed PLWH with INR, primarily through memory subset expansion and modulation of IP-10/CXCL10 inflammatory signaling, supporting its potential as an adjunctive immunomodulatory strategy.

Fanconi anemia complement group I (FANCI), a core component of the Fanconi anemia pathway, has emerged as a potential oncogenic factor across multiple cancer types. Located on chromosome 15q26.1, FANCI encodes a protein named FANCI that forms a stable heterodimer with FANCD2, playing a central role in the DNA damage response and repair. Beyond its involvement in DNA repair, FANCI participates in ribosome biogenesis, meiosis, and mRNA export, underscoring its essential role in maintaining genomic stability. Although FANCI deficiency has traditionally been associated with Fanconi anemia, recent studies have demonstrated that FANCI is overexpressed in various malignancies, where it promotes tumor progression and correlates with poor prognosis. The expression and activity of FANCI are tightly regulated at multiple levels, including transcriptional and post-transcriptional regulation by transcription factors and non-coding RNAs, as well as post-translational modifications such as phosphorylation mediated by PP2A and ATR, monoubiquitination catalyzed by the FANCL–UBE2T complex, and deubiquitination by USP1-UAF1. This review summarizes the functional mechanisms of FANCI across diverse physiological and pathological processes, highlighting its role as a crucial molecular bridge linking genomic stability maintenance to cancer development, and emphasizing its potential as a promising therapeutic target in cancer.

The very low-density lipoprotein receptor (VLDLR), a member of the low-density lipoprotein receptor superfamily, mediates the endocytosis of very-low-density lipoproteins and participates in a wide range of physiological and pathological processes, including neurodevelopment, viral infection, and angiogenesis. Recent studies have shown that VLDLR facilitates alphavirus entry and exhibits a distinct spatiotemporal expression pattern in the liver. This review summarizes the structural features of VLDLR and systematically evaluates its multifaceted roles: mediating viral entry; promoting hepatic VLDL uptake to lower circulating lipid levels; transducing Reelin signaling for cortical and cerebellar lamination; suppressing pathological retinal angiogenesis; and modulating cancer progression. These insights provide a comprehensive overview of the versatile functions of VLDLR.

ATG9A is the only transmembrane protein among the components required for autophagosome formation and participates in multiple cellular biological processes. ATG9A undergoes intracellular transport via microtubules and actin. As a lipid scramblase, ATG9A facilitates the random movement of lipid molecules between the inner and outer leaflets of lipid bilayers. Additionally, it can influence the homeostasis of the plasma membrane and membranous organelles. In autophagy, ATG9A is recruited to autophagic initiation sites to initiate cellular autophagy and subsequently participates in the process by promoting lipid transfer. Moreover, ATG9A also plays roles in maintaining neuronal homeostasis and is involved in embryonic development, infection, and immune responses. In this review, we comprehensively and systematically summarize the roles and mechanisms of ATG9A, aiming to provide a new perspective for understanding its functions.

Background:The long-term impact of low-level viremia (LLV), defined as two consecutive viral loads (VL) of <200 copies/mL, on virological failure remains unclear. This study aimed to investigate the association between viremia patterns and virological failure in people living with HIV (PLWH) in China who predominantly received non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapies. Methods:Data from six HIV-infected cohorts in China were analyzed. Adult antiretroviral therapy (ART)-naïve patients were included. Patients were excluded if they received less than 24 weeks of ART, had fewer than two documented VL and CD4+ T cell count, initiated ART during the acute infection stage, or had a follow-up duration of less than 48 weeks. All patients were stratified according to virological suppression (VS), virological blips (VB), or LLV. Cox regression analysis was used to evaluate the association between virological failure and patterns of viremia. Genotypic drug resistance mutations were compared at baseline and during LLV. Results:Among the 1532 patients, 374 (24.4%) had blips and 166 (10.8%) had LLV. The LLV group had a higher baseline viral load and lower CD4+ T cell count. Approximately 90% of patients received NNRTI-based regimens. In the adjusted Cox regression, neither the blip nor LLV groups demonstrated a significantly increased risk of virological failure compared to the VS group (Blip, adjusted HR = 0.5 [95% CI: 0.2-1.2], p = 0.116; LLV, aHR = 0.7 [95% CI: 0.3-1.9], p = 0.474). Among the 17 patients who successfully underwent sequencing, three (17.6%) developed new drug resistance mutations, but none experienced virological failure. Conclusion:Neither blip nor LLV were significantly associated with an increased risk of virological failure in China. Emerging drug resistance mutations in LLV are rare and do not correlate with subsequent virological failures. Further research is needed to understand the clinical significance of these patterns of viremia.

BACKGROUND:Pancytopenia, a severe hematologic comorbidity, raises significant clinical concern for increased morbidity and mortality in people living with HIV (PLWH). However, reports on its incidence, risk factors, real-world etiologies, longitudinal characteristics, or management strategies in PLWH are absent. Through a long-term study of a large Asian cohort, this work aims to provide insights into these aspects. METHODS:We conducted a nested case-control study involving 1586 PLWH visiting our institution from January 2000 to March 2023. Cases experienced at least one pancytopenia episode, while controls with no such history were matched by age, sex, and HIV transmission route. Demographic, clinical, and laboratory data were analyzed to identify risk factors, etiologies, clinical features, and outcomes regarding pancytopenia. RESULTS:Pancytopenia occurred for 1-3 times in 82 patients (5.17 %), with an annual incidence of 2.82 % and a prevalence of 3.71 %. Advanced disease (WHO Stage 3-4) was an independent risk factor (aOR 2.88, 95 % CI 1.07-7.78, P = 0.03). The leading etiologies of pancytopenia included advanced HIV infection (36.3 %) and medication toxicity (36.3 %); co-infection and malignancy contributed to fewer cases. The majority of pancytopenia episodes occurred once per patient, typically within the early years of HIV diagnosis, did not require hospitalization, and could be resolved with a median of 21 weeks. Resolution of pancytopenia was accompanied by viral control and immune recovery. However, life-threatening anemia (Hgb<65 g/L) was a significant predictor for irreversibility (P = 0.035). A history of pancytopenia significantly impaired patient survival (P = 0.008). CONCLUSIONS:Caution is warranted for the occurrence of pancytopenia in PLWH, particularly those with advanced disease. Effective antiretroviral therapy and medication review should be prioritized in managing pancytopenia, along with individualized screening for underlying opportunistic conditions. Attention is needed for patients with a history of pancytopenia due to poorer prognosis.

Abstract Background The prevalence of cardiac dysfunction in people living with HIV (PLWH) on long-term combination antiretroviral therapy (cART) in Asia remains unclear. This study sought to investigate the prevalence of echocardiographic dysfunction in Chinese PLWH on long-term cART and explore related risk factors. Methods The Chinese Long-Term Antiretroviral Treatment (CLTA) study is a multi-center, prospective cohort study aimed to determine the comorbidities in PLWH treated on long-term cART. 371 PLWH on long-term cART were enrolled in the echocardiographic substudy. 268 cART-Naïve PLWH and 110 HIV-negative individuals were included as control groups after being matched for gender, age and blood pressure. The prevalence of left ventricular systolic dysfunction (LVSD), pulmonary arterial hypertension (PAH) and left ventricular hypertrophy (LVH) was assessed and compared between different groups. Results The median age of the long-term CART (CLTA) group was 41.1 years (83.3% male). The CLTA participants had received cART for a median of 6.2 years with a current CD4+ T cell count 509 cells/mm3. 99.1% of them were viral suppressed. The prevalence of LVSD, PAH and LVH in the CLTA group was 1.1%, 3.9%, 10.3%, respectively. Among 268 pairs of CLTA and cART-Naïve PLWH, CLTA group had a significantly lower prevalence of PAH (4.0% vs 12.7 %, P=0.010). Among 110 pairs of CLTA and HIV-negative controls, the CLTA group had a significantly higher prevalence of LVH than HIV-negative controls (23.8% vs 5.5%, P=0.004). Incomplete immune reconstitution (CD4 <350 cells/mm3, OR=4.286, P=0.007), female gender (OR=18.014, P<0.001) and elevated triglycerides (OR=1.199, P=0.008) were associated with increased risk of LVH in PLWH on long-term cART. Conclusions In this Chinese PLWH on long-term cART cohort, the prevalence of LVSD and PAH are relatively low. Compared with HIV-negative controls, PLWH on long-term cART had a higher prevalence of LVH, which is associated with both traditional CVD risk factors and incomplete immune reconstitution. Trial Registration The study was registered in ClinicalTrials.gov (NCT04463810)

Several studies have reported that combination antiretroviral therapy (cART) enhances the hepatitis B surface antigen (HBsAg) clearance rate in Human Immunodeficiency Virus-1/Hepatitis B Virus (HIV/HBV) coinfected patients, yet the associated immunological characteristics remain unclear. Global and specific immune phenotypic profiles were examined in 48 patients with HIV/HBV coinfection before cART and at 1-year, and 3-year after cART using flow cytometry. In addition, 61 patients with HBV monoinfection were included for comparison. HBsAg response (sAg-R) was defined as > 0.5 log decrease within six months of cART initiation, and 16 patients achieved it. Patients with sAg-R (the sAg-R group) exhibited distinct immune phenotypes compared to those of HBsAg-retained patients (the sAg-NR group). Notably, patients with sAg-R had lower CD4+ T cell counts and a higher number of HBcAg-specific T cells. Further, the sAg-R group exhibited upregulation of HLA-DR, Ki67, and PD-1 in CD4+ T cells and heightened HLA-DR and T-bet in CD8+ T cells. However, the sAg-R group had fewer TEMRA cells but more TEM and Th17 cells than those in the sAg-NR group. Expression of various markers, including HLA-DR+CD4+, Ki67+CD4+, PD-1+CD4+, CD38+CD8+, HLA-DR+CD8+, TIM-3+CD8+, HBV-specific CD4+ T cell secreting IFN-γ and IL-2, and specific CD8+ T cell secreting IFN-γ and IL-2, correlated with HBsAg decrease. The decline in HBsAg levels during cART in HIV/HBV coinfection involves significant alterations in CD4+ and CD8+ T cells phenotypes, offering a novel perspective on a functional HBV cure.

This is the first study to report both greater BMD loss and muscle loss in Chinese HIV-infected males with lamivudine (3TC)-tenofovir disoproxil fumarate (TDF)-efavirenz (EFV) regimen, which highlights the importance of closely monitoring muscle mass and bone mineral density in patients treated with 3TC-TDF-EFV regimen and provides a foundation for the clinical intervention of sarcopenia and osteoporosis. To compare the effect initiating different antiretroviral therapy (ART) regimens have on muscle mass, bone mineral density (BMD), and trabecular bone score (TBS). We designed a retrospective study of ART-naive Chinese males with HIV (MWH) undergoing two different regimens at 1-year follow-up. All subjects underwent dual-energy absorptiometry (DXA) for BMD and muscle mass prior to ART initiation, and again 1 year later. TBS iNsight software was used for TBS. We analyzed differences in muscle mass, BMD, and TBS after different treatment arms and associations between ART regimens and changes in them. A total of 76 men were included (mean age 31.83 ± 8.75 years). Mean absolute muscle mass decreased significantly from baseline to follow-up after initiation of lamivudine (3TC)-tenofovir disoproxil fumarate (TDF)-efavirenz (EFV), whereas increased significantly after initiation of 3TC-zidovudine(AZT)/Stavudine(d4T)-Nevirapine(NVP). Assignment to 3TC-TDF-EFV resulted in greater percentage loss in BMD at lumbar spine (LS) and total hip (TH) compared to 3TC-AZT/d4T-NVP, but this difference was not statistically significant at the femoral neck BMD and TBS. In the multivariable logistic regression model adjusted for covariates, the 3TC-TDF-EFV regimen was associated with higher odds of decreased appendicular and total muscle mass, LS and TH BMD. This is the first study to report not only greater BMD loss but also muscle loss in Chinese MWH with 3TC-TDF-EFV regimen. Our work highlights the importance of closely monitoring muscle mass and BMD in patients treated with 3TC-TDF-EFV regimen and provides a foundation for the clinical intervention of sarcopenia and osteoporosis in them.

Background: Understanding immune responses after HBV vaccination is important to prevent HBV infection in PLWH and to achieve successful treatment. Methods: Thirty-two PLWHs with CD4+ cell count > 350 cells/µL and HIV RNA < 200 copies/mL were vaccinated with 20 µg of HBV vaccine at weeks 0, 4, and 24 in this prospective study. We measured total HIV DNA levels, HBsAb titers and HBsAg-specific T-cell responses during follow-up time. Results: All patients achieved protective HBsAb titer after immunization. The magnitude of the IFN-r and TNF-a response to HBsAg was 22.0 (IQR: 6.5–65.0) and 106.50 (IQR: 58.5–203.0) spot-forming cells (SFC)/105 PBMC, respectively at week 0. The level of IFN-r secreted at weeks 12 and weeks 36 to 48 was comparable with that at week 0. However, IFN-r response was higher at weeks 12 than that at weeks 36 to 48 (p = 0.02). The level of TNF-a secreted at weeks 12 was higher than that at week 0 (p < 0.001). Total HIV DNA levels were 2.76 (IQR: 2.47–3.07), 2.77 (IQR: 2.50–3.09), 2.77 (IQR: 2.41–2.89) log10 copies/106 PBMCs at weeks 0, 12, 36 to 48, respectively. No correlation was observed between IFN-r and TNF-a levels and HBsAb titer as well as total HIV DNA levels after immunization. Conclusion: Humoral immunity was satisfactory, but cellular immunity and decline in HIV reservoir were not optimal after HBV vaccine immunization in these patients.

Abstract Background The study aimed to investigate the relationship between muscle mass, bone mineral density (BMD) and trabecular bone score (TBS) in Chinese HIV-infected males. Methods We designed a retrospective and cross-sectional study of Chinese males with HIV. Muscle mass and BMD were measured by dual-energy X-ray absorptiometry (DXA). TBS iNsight software was used for TBS. Multiple linear regression was used to evaluate the correlations between bone parameters and muscle mass after adjusting for confounding variables. Results A total of 295 males were included in the study (mean age 36.49 ± 11.16 years). Low muscle mass and abnormal bone microarchitecture were observed in 105/295 (35.6%) and 96/295 (32.5%) patients, respectively. Men with low muscle mass had lower BMDs, T-scores, muscle mass and fat mass at all the evaluated sites, lower Z-score at total hip (TH) and lower percentage fat mass (PFM) than their counterparts. In the multiple linear regression model adjusted for age, BMI, CD4 + cell count, viral load, treatment status and PFM, appendicular skeletal muscle mass index (ASMI) was positively correlated with BMDs at lumbar spine (LS) and TH. Conclusions Low muscle mass is more common than low bone mass/ abnormal bone microarchitecture in Chinese HIV-infected males. The reduction of muscle mass was significantly associated with decreased bone mass, particularly at LS and TH.

Background:Several studies have described the rapid decline and clearance of hepatitis B surface antigen (HBsAg) in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfection after initiating combined antiretroviral therapy (cART). Early decline of HBsAg levels is associated with HBsAg seroclearance in the treatment of chronic HBV infection. This study aims to evaluate the HBsAg kinetics and the determinants of early HBsAg decline in patients with HIV/HBV coinfection during cART.Methods:A total of 51 patients with HIV/HBV coinfection were enrolled from a previously established HIV/AIDS cohort and followed for a median of 59.5 months after cART initiation. Biochemical tests, virology and immunology assessments were measured longitudinally. The kinetics of HBsAg during cART were analyzed. Soluble programmed death-1 (sPD-1) levels and immune activation markers (CD38 and HLA-DR) were measured at baseline, 1-year and 3-year during treatment. HBsAg response was defined as a decline of more than 0.5 log10 IU/ml at 6 months from the baseline after initiation of cART.Results:HBsAg declined faster (0.47 log10 IU/mL) in the first six months and attained a decrease of 1.39 log10 IU/mL after 5-year therapy. Seventeen (33.3%) participants achieved a decline of more than 0.5 log10 IU/ml at the first 6 months of cART(HBsAg response) of which five patients achieved HBsAg clearance at a median of 11 months (range: 6-51 months). Multivariate logistic analysis showed the lower baseline CD4+ T cell levels (OR=6.633, P=0.012) and sPD-1 level (OR=5.389, P=0.038) were independently associated with HBsAg response after cART initiation. The alanine aminotransferase abnormality rate and HLA-DR expression were significantly higher in patients who achieved HBsAg response than in those who did not achieve HBsAg response after cART initiation.Conclusion:Lower CD4 + T cells, sPD-1, and immune activation were related to a rapid HBsAg decline in patients with HIV/HBV-coinfection after the initiation of cART. These findings imply that immune disorders induced by HIV infection may disrupt immune tolerance to HBV, leading to a faster decline in HBsAg levels during coinfection.

Abstract Background Cytomegalovirus (CMV) was the common opportunistic pathogen among people living with HIV(PLWH), even in the combination antiretroviral therapy (ART) era. This study aimed to report the epidemiology and characteristics of CMV coinfection among Chinese PLWH. Methods Data were collected from two prospective longitudinal multicenter cohorts of PLWH initiating combination antiretroviral therapy (cART) from 2010 to 2015. This study extracted laboratory parameters, clinical symptoms, and serology of CMV baseline to 192 weeks of cART. Results 1552 patients were included in this analysis; the prevalence of CMV coinfection was 3.53% before cART. Logistics analysis showed that patients with lower CD4 T cell counts, RPR-seropositive, infected through homosexual contact, and from southern China had a higher risk of CMV/HIV coinfection at baseline. Patients with CMV coinfection at baseline had lower CD4/CD8 ratios at baseline (0.29 vs 0.22, p = 0.006), 96 weeks (0.63 vs 0.51, p = 0.015). After initiation of cART, the incidence of CMV recent infection was 10 cases/1000 PY. Cases coinfected with CMV during cART were mostly asymptomatic and had a comparable CD4, CD8 T cell counts, and CD4/CD8 ratio to non-coinfected patients. Conclusion This multicenter study reported a national prevalence and incidence of CMV recent infection among the Chinese PLWH before or on cART. CMV coinfection before cART initiation was associated with a slower recovery of CD4/CD8 ratio. However, CMV coinfection during successful treatment cART seems not to affect immunity parameters.