BACKGROUND:Kaposi sarcoma (KS) is one of the most common tumors in patients with AIDS, while the occurrence of chylous effusions in KS patients is rare and often indicates a poor prognosis. This report present a case of successfully treated AIDS-associated KS complicated by both chylothorax and chylous ascites, along with a review of the relevant literature. CASE PRESENTATION:A 31-year-old male patient, who was recently diagnosed with HIV infection and oral KS at our clinic center, returned two weeks post-discharge. He reported significant enlargement of the oral tumor, increased abdominal girth with accompanying abdominal distension and pain, and a dry cough over the past week. Upon readmission, CT scans indicated the presence of extensive pleural and abdominal effusions. Aspirates from both the pleural and abdominal effusions exhibited a milky chylous appearance. After eliminating other potential etiologies for the chylous effusion, we associated it with the progression of KS. The patient's condition was ultimately successfully managed through a combination of antiretroviral therapy, systemic chemotherapy, and ntermittent thoracoabdominal paracentesis for drainage. CONCLUSIONS:The development of chylous effusions in patients with AIDS-associated Kaposi sarcoma signifies disease progression. Prompt initiation of systemic chemotherapy combined with antiretroviral therapy is critical for improving outcomes.

Probe-Capture Metagenomics is a newly developed method for detecting infectious pathogens. However, its application in HIV-infected patients with pulmonary infection remains limited. This study utilized Probe-Capture Metagenomics to analyze lung microbiomes and Drug Resistance Mutations of HIV and bacteria in people living with HIV (PLWH) with pneumonia. We retrospectively investigated lung microorganisms in PLWH hospitalized at Zhongnan Hospital of Wuhan University. A combination of bronchoalveolar lavage fluid Probe-Capture Metagenomics and conventional microbiological tests were performed in all patients. A total of 91 patients were included in the study. Excluding the EB and Torque teno virus, at least two organisms were identified in 85 patients using Probe-Capture Metagenomics combined with conventional microbiological tests. The top six detected organisms were CMV, Pneumocystis jirovecii, Mycobacterium tuberculosis complex, HHV-7, Candida albicans and Aspergillus. For specific organisms, the detection rate of CMV and Candida albicans by Probe-Capture Metagenomics was significantly higher than that of conventional microbiological tests (p < 0.0001). Moreover, the detection rates of CMV (p = 0.0167) and Pneumocystis jirovecii (p = 0.04) in patients with CD4+T count ≥ 200 cells/μL were higher than that with CD4+T count < 200 cells/μL. Importantly, Probe-Capture Metagenomics can uncover potentially clinically relevant drug-resistance mutations linked to HIV and bacteria. Probe-Capture Metagenomics provides a promising method of detecting suspected opportunistic infections in PLWH with pneumonia, especially for mixed infections and rare microorganisms. In addition, Probe-Capture Metagenomics was a potential valuable tool for genotyping resistance testing of HIV and bacteria.

To develop a risk prediction model for hepatocellular carcinoma (HCC) by screening differentially expressed proteins (DEPs) in HIV/HBV coinfected patients with HCC and liver cirrhosis using proteomic techniques. DEPs were identified in plasma from HIV/HBV co-infected patients with HCC and liver cirrhosis using quantitative liquid chromatography-mass spectrometry (LC-MS). Mapping discovered proteins to the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO) databases yielded annotation information for DEPs. Differential plasma apolipoprotein A-1(APOA1) and transthyretin (TTR) expression levels were validated in 88 HIV/HBV co-infected individuals with HCC and liver cirrhosis. In total, 150 DEPs were discovered. The GO entries were primarily enriched for cutaneous immunological response mediated by circulating immunoglobulin and complement activation, as well as lipoprotein particle. The KEGG pathway enrichment was dominated by complement and coagulation cascades. Six of the 15 items enriched in the DO entries were related to lipid metabolism. APOA1, TTR, Prothrombin (F2), Antithrombin-III (SERPINC1), Alpha-2-HS-glycoprotein (AHSG), Alpha-2-macroglobulin (A2M) and Haptoglobin-related protein (HPR) were finally identified as hub proteins. Finally, a visual logistic model using immunoglobulin heavy variable 3-13 (IGHV3-13) and A2M to predict HCC were constructed. Significant variations in plasma APOA1 and TTR levels were found in HIV/HBV co-infected patients with HCC and liver cirrhosis. The screened hub proteins from DEPs can be employed as possible markers for early HCC detection. The developed HCC prediction model can be used to assess the risk of HCC in HIV/HBV co-infected cirrhotic individuals.

BACKGROUNDS:To evaluate the role of guanylate-binding protein 6 (GBP6) in esophageal cancer (ESCA). METHODS:We comprehensively evaluated the expression pattern, clinical features, prognostic role, biological functions, and immunological role of GBP6 based on the public databases. Immunohistochemistry was used to validate the results in an ESCA tissue microarray. The proliferative activity of ESCA cells was evaluated using cell counting kit 8 assay. The cell cycle changes were determined using flow cytometry. We also analyzed potential compounds for combination therapy with GBP6. RESULTS:Among the GBPs family, we found that GBP6 was only specifically expressed in the normal oropharyngeal tract, while its expression was downregulated in ESCA tissues. Patients with low expression of GBP6 was associated with poor prognosis, worse grade and TNM stage. However, no significant relationship between GBP6 and the immune microenvironment in ESCA. Enrichment analysis showed that GBP2-high expression group was significantly enriched in the p53 signaling pathway. Then, we found that knockdown of GBP6 expression inhibited the proliferative of ESCA cells and induced the cell cycle arrest. Moreover, the expression of p53, p21, and p27 were also downregulated in the GBP6 knockdown group. Finally, drug response prediction revealed that several small molecule compounds may have better anti-cancer effects in samples with high expression of GBP6. CONCLUSION:The GBP6 could be a potential prognostic therapeutic target for ESCA treatment.

Easily accessible clinical warning signals of liver cirrhosis for optimal management in people living with HIV/HBV co-infection remains limited. Using proteomic techniques, a risk prediction model for liver cirrhosis through the screening of differentially expressed proteins (DEPs) in people living with HIV/HBV coinfection was developed. Quantitative liquid chromatography-mass spectrometry (LC–MS) was used to identify DEPs in plasma collected from HIV/HBV co-infected patients with or without liver cirrhosis. The annotation information of DEPs were obtained by mapping identified proteins to the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes(KEGG), and Disease Ontology(DO) databases. Differential expression levels of plasma L-selectin(CD62L) were validated in HIV/HBV co-infected patients. Proteomic profiling of 13 matched patient pairs with HIV/HBV coinfection revealed 111 differentially expressed proteins (DEPs) associated with liver cirrhosis. Functional analysis showed significant enrichment in immune processes and the Complement and Coagulation Cascades pathway, underpinning the chronic inflammatory and fibrotic aspects of the disease. A diagnostic signature derived from these DEPs was developed, with a model containing IGHV5-37 and L-selectin showing high predictive value. Critically, the elevated plasma level of L-selectin in cirrhosis was confirmed in a separate validation cohort of 90 patients, underscoring its clinical relevance. Our findings demonstrate that cirrhosis in HIV/HBV coinfected patients is characterized by a specific plasma proteomic profile. From this profile, we derived and validated a diagnostic model, highlighting L-selectin as a key validated biomarker. This model holds significant promise for development into a clinical assay to improve the detection and management of liver disease in this high-risk population. Not applicable

Objective To analyze the clinical characteristics of AIDS complicated with heterogeneous multiple primary malignant tumors (MPMTs), and to provide clinical accumulation for the diagnosis and treatment of AIDS complicated with malignant tumor and improve prognosis.Methods The clinical features, treatment and prognosis of 6 cases of AIDS complicated with heterogeneous MPMTs were analyzed retrospectively.Results The first primary malignant tumor of the 6 AIDS patients was non-Hodgkin lymphoma (2 cases), skin cancer (2 cases), cervical cancer (1 case) and laryngeal cancer (1 case), respectively. The median age was 49(43, 58) years old, and the median CD4 cell count was 100 (55, 306) /μL. The second primary tumor was lung cancer (2 cases), colon cancer (2 cases), gastric cancer (1 case), and parotid gland malignancies (1 case), with an average CD4 cell count of (354±177) cells/μL. The mean interval between the two primary malignancies was (67±53) months, and three patients with gastrointestinal malignancies died at the end of follow-up, with a survival time of 3-9 months.Conclusion The AIDS patients with malignant tumors should be followed up regularly for a long time and be vigilant about the occurrence of MPMTs. Regular gastroenteroscopy can reduce the risk of malignant tumors of digestive tract and is expected to improve the prognosis.

Combination antiretroviral therapy (ART) has improved outcomes for human immunodeficiency virus (HIV) associated non-Hodgkin lymphoma. This is an analysis of 127 patients with HIV with Burkitt lymphoma (HIV-BL) and diffuse large B-cell lymphoma (HIV-DLBCL) treated at the Zhongnan Hospital of Wuhan University over a 17-year period during the ART and rituximab era. The median CD4 count for the cohorts was 0.141 × 109/L (range, 0.001-0.861 × 109/L). DA-EPOCH ± R (54%) were most commonly used in HIV-BL. CHOP± R (42%) was most commonly used to treat HIV-DLBCL. The complete response rate after first-line curative therapy was 10/28 (36%) in HIV-BL and 25/57 (44%) in HIV-DLBCL. The 2-year progression-free survival (PFS) and overall survival (OS) for the HIV-BL cohort was 50% and 41% respectively. The 2-year PFS and OS for the HIV-DLBCL cohort was 55% and 47% respectively. Current China practice favours the treatment of HIV-BL and HIV-DLBCL similarly to the HIV-negative population with the use of concurrent ART. However, due to the extremely low percentage of patients receiving ART prior to the lymphoma diagnosis, the high percentage of patients with poor performance status, and the advanced stage at diagnosis, the treatment of HIV-related lymphoma remains the major challenge in China.

Objective The immune responses of COVID-19 convalescent patients have not been well described. Methods Blood from thirty COVID-19 convalescent patients who were virus-free were collected. Their clinical laboratory findings and SARS-CoV-2-specific humoral and cellular immunity were detected. Results At 283 days after diagnosis of SARS-CoV-2 infection, the levels of clinical laboratory indicators and lymphocyte subtypes returned to normal levels. However, the ratio of memory/naive CD4+ T lymphocytes cells was greater in COVID-19 convalescent patients and severe COVID-19 convalescent patients, when compared with that in healthy blood donors (P=0.0135) and non-severe patients (P=0.0431), respectively. The levels of anti-SARS-CoV-2-IgM (P=0.014), S1-IgM (P=0.0004) and RBD-IgM (P=0.0002) in severe COVID-19 patients were all significantly greater than those in non-severe COVID-19 patients. When the serums of COVID-19 convalescent patients were diluted as 1:125, the predictive of serum neutralization capabilities were persistent in all patients. SARS-CoV-2-specific T cells were generated and maintained in majority of tested convalescent COVID-19 patients, regardless of the severity of disease in acute phase. Conclusion At 283 days after diagnosis of SARS-CoV-2 infection, specific cellular and humoral immunity against SARS-CoV-2 could be detectable. The severity of disease in acute phase cannot affect the strength of cellular and humoral immunity in convalescent phase.

IntroductionThis study aimed to assess the diagnostic values of bronchoalveolar lavage fluid (BALF) real-time polymerase chain reaction (PCR) and BALF metagenomic next-generation sequencing (mNGS) for Pneumocystis jirovecii pneumonia (PJP) in patients infected with human immunodeficiency virus (HIV).MethodsA total of 99 HIV-infected PJP patients and 61 HIV-infected patients diagnosed with non-PJP pneumonia between March 2019 and December 2022 were enrolled. P. jirovecii and multiple other co-pathogens detected in BALF by mNGS were analyzed. The clinical final diagnosis was employed as a benchmark. We compared the diagnostic performance of mNGS in PJP with serum BDG and BALF real-time PCR. The mixed infections detected by mNGS and modifications of antimicrobial treatment were also analyzed.ResultsThe sensitivity of mNGS test of BALF samples reached 85.86%, which was significantly higher than serum BDG (39.39%, P < 0.001). The sensitivity of BALF P. jirovecii PCR (84.85%) was similar with mNGS (P > 0.05). The specificity of mNGS (100%) was also same as PCR (100.0%), and superior to serum BDG (88.52%, P < 0.001). Besides, mNGS performs remarkably well in identifying co-pathogens of PJP patients infected with HIV. In addition to P. jirovecii, 82 cases (82.83%) of other co-pathogens were identified based on mNGS. Moreover, thirty-four patients (34.34%) increased therapeutic dose of trimethoprim-sulfamethoxazole (TMP-SMZ) based on BALF P. jirovecii PCR. Based on the mNGS results, initial antimicrobial treatment was modified in 86.87% (86/99) of PJP patients.ConclusionBALF mNGS and real-time PCR are two powerful techniques for rapid diagnosis of PJP with high specificity and sensitivity. Moreover, the benefit of mNGS is that it may identify other organisms besides PJP and it may benefit proper and prompt treatment.

目的:探讨艾滋病合并霍奇金淋巴瘤（HL）、肝衰竭及肺结核病的诊断与治疗。方法:回顾性分析2022年1月武汉大学中南医院收治的1例艾滋病合并HL、肝衰竭及肺结核患者的诊治经过，并复习相关文献。结果:患者，31岁，男性，艾滋病合并肺结核，抗结核治疗效果不佳。经多次淋巴结病理活组织检查，最终诊断为HL。抗肿瘤治疗后患者病情好转，后续抗结核及抗艾滋病治疗使患者进一步好转。结论:病理活组织检查在艾滋病合并HL及肺结核的诊断中发挥重要作用，且当判断肿瘤是影响患者转归的主要因素时，应积极行抗肿瘤治疗。

To evaluate clinical value of metagenomic next-generation sequencing (mNGS) in people living with HIV/AIDS (PLWHA) who had CNS disorders. Cerebrospinal fluid (CSF) samples from 48 PLWHA presenting with CNS disorders were sequenced using mNGS and compared with clinical conventional diagnostic methods. In total, 36/48 ss(75%) patients were diagnosed with pathogen(s) infection by mNGS, and the positive detection proportion by mNGS was higher than that by clinical conventional diagnostic methods (75% vs 52.1%, X 2 = 5.441, P = 0.020). Thirteen out of 48 patients (27.1%) were detected with 3–7 pathogens by mNGS. Moreover, 77 pathogen strains were detected, of which 94.8% (73/77) by mNGS and 37.0% (30/77) by clinical conventional methods ( X 2 = 54.206, P < 0.001). The sensitivity and specificity of pathogens detection by mNGS were 63.9% (23/36) and 66.7% (8/12), respectively, which were superior to that by clinical conventional methods (23/36 vs 9/25, X 2 = 4.601, P = 0.032; 8/12 vs 5/23, X 2 = 5.029, P = 0.009). The application of mNGS was superior for its ability to detect a variety of unknown pathogens and multiple pathogens infection, and relatively higher sensitivity and specificity in diagnosis of CNS disorders in PLWHA.

Objective:To investigate the prevalence of liver fibrosis in patients with HBV infection detected by ultrasound transient elastography.Methods:A total of 2 689 patients with HBV infection who received liver transient elastography examination at the Department of Hepatology, Zhongnan Hospital of Wuhan University from November 2021 to April 2022 were enrolled in the study. The severity of liver fibrosis was graded according to the liver stiffness value. The association of liver fibrosis detection rate with gender, age and physiological stages of patients was analyzed, and the correlation between liver stiffness value and HBV DNA, HBsAg, HBeAg level, alanine aminotransferase (AST), aspartate aminotransferase (ALT) and serum albumin levels was further analyzed.Results:Among 2 689 patients with chronic HBV infection, there were 1 417 males aged 46 (34, 57) years and 1 272 females aged 45 (33, 55) years. A total of 1 382 patients (51.03%) showed varying degrees of liver fibrosis, including 381 cases (14.20%) of significant liver fibrosis and 259 (9.60%) cases of progressive fibrosis. Male patients had a significantly higher prevalence of liver fibrosis than that of female patients [60.78%(840/1 382) vs. 39.22%(542/1 382), χ2=74.566, P<0.001]. There were significant differences in liver stiffness values and liver fibrosis detection rates ( F=46.516, 199.079, P<0.001) among patients of different age groups. The liver stiffness index (9.41±4.49 vs. 8.10±3.89, t=9.011, P<0.001) and the prevalence of liver fibrosis in males was higher than those in females in age groups younger than 60 years [61.59%(643/1 044) vs. 38.41%(401/1 044), χ2=78.418, P<0.001]; However, there was no significant gender difference in people over 60 years of age [73.80%(200/271) vs. 71.71%(142/198), χ2=0.252, P>0.05; 20.30%(55/271) vs. 21.21%(42/198), χ2=0.059, P>0.05]. The prevalence of liver fibrosis was significantly lower in premenopausal and perimenopausal females than that in males of the same age groups [29.70%(188/633)and 52.20%(154/295) vs. 64.50%(202/313), χ 2=56.683, P<0.001; χ 2=9.519, P=0.029], whereas there was no significant difference between postmenopausal females and males in the same age group [65.40%(220/336) vs. 72.20%(319/441), χ 2=5.822, P=0.061]. The prevalence of liver fibrosis increased significantly in postmenopausal females as compared to premenopausal females[38.40%(497/1 294) vs. 67.50%(532/787), χ 2=56.683, P=0.002]. The value of liver stiffness in patients with chronic HBV infection was positively correlated with total bilirubin, AST and ALT levels( r=0.208, 0.227, 0.218, P<0.05). Conclusions:The prevalence of liver fibrosis detected by ultrasound transient elastography in chronic HBV-infected patients is substantial, the liver stiffness value and detection rate are higher in males than those in females, however, the prevalence is increased in postmenopausal females. The liver stifness value is related to some biochemical indicators of the liver.

Objective:To evaluate the clinical value of metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid in acquired immune deficiency syndrome (AIDS)? complicated with central nervous system (CNS) infection, and to investigate the pathogetic spectrum.Methods:AIDS patients complicated with CNS infection in Zhongnan Hospital of Wuhan University from January 2021 to August 2022 were analyzed, including the clinical characteristics and pathogen information detected by mNGS and routine etiological examination. The pathogens detected by routine etiological examination and mNGS were compared, and the consistency with clinical diagnosis was evaluated.Results:Among the 61 patients with CNS infection, 60 patients (98.4%, 60/61) were identified by mNGS combined with routine etiological examination, which was significantly higher than that of routine etiological examination alone (49.2%, 30/61) and that of mNGS alone (83.6%, 51/61), with significant differences (χ2 = 38.125, P < 0.001; χ2 = 8.093, P = 0.004). The positive rate of mNGS 83.6% (51/61) was significantly higher than that of routine etiological examination [49.2% (30/61)], with significant difference (χ2 = 16.201, P < 0.001). The detection rate of two or more pathogens by mNGS was 41.0% (25/61), which was significantly higher than that by routine etiological examination (9.8%, 6/61), with significant difference (χ2 = 15.612, P < 0.001). For the detection rate of cryptococcal meningitis, conventional detection method [14.8% (9/61)] was in good agreement with mNGS [13.1% (8/61)], and the consistency with clinical diagnosis were 90% (9/10) and 80% (8/10), respectively. At least one virus was detected in 43 (70.5%) patients, of which 24 (39.3%) cases detected human herpesvirus 4 (EBV), 15 (24.6%) cases detected human herpesvirus 5 (CMV), and 8 (13.1%) cases detected JC polyomavirus. Total of 18 strains of fungi were detected in 14 (23.0%) patients, including 8 strains of Cryptococcus neoformans, 4 strains of Aspergillus, 3 strains of Candida parapsilosis, 1 strain of Talaromyces marneffei, 1 strain of Pneumocystosis jirovecii and 1 strain of Dosporium apiospermum. There were 8 (13.1%) atypical pathogens detected, including 3 strains of Toxoplasma gondii, 3 strain of Treponema pallidum, 1 strain of Legionella and 1 strain of Rickettsia felis. Tuberculosis and non-tuberculous mycobacterium were detected in 2 (6.6%) cases respectively. Total of 3 cases died, the mortality rate was 4.9% (3/61).Conclusions:Mixed infections are common in advanced AIDS patients complicated with CNS infection, and the pathogetic spectrum includes virus, fungi, bacterial and atypical pathogens. mNGS combined with routine etiological examination could significantly improve the rapid pathogen detection rate of intracranial infections and the survival rate of patients.

乙型肝炎病毒(HBV)再激活是HBV感染的肿瘤患者接受化疗期间常见并发症,轻者表现为无症状的自限性肝炎,重者出现急性肝衰竭而死亡.HBV表面抗原(HBsAg)阳性合并血液系统恶性肿瘤患者化疗后HBV再激活率高于其他肿瘤,约为 24％～53％[1].故血液肿瘤合并HBV感染者在接受化疗或骨髓移植前服用核苷(酸)类似物预防HBV再激活已获广泛共识.

Objective:To summarize the clinical features and survival differences between human immunodeficiency virus (HIV)-positive and HIV-negative cervical cancer patients, and to explore the factors influencing the prognosis.Methods:The clinical data of patients with cervical cancer diagnosed and treated in Zhongnan Hospital of Wuhan University from January 2015 to January 2022 were retrospectively analyzed. There were 46 HIV-positive cases and 587 HIV-negative cases; all 46 HIV-positive patients had squamous cell carcinoma, while 504 HIV-negative patients had squamous cell carcinoma. According to age and clinical staging, 230 HIV-negative squamous cell carcinoma patients were screened to match with 46 HIV-positive squamous cell carcinoma patients according to 1∶5. The clinical features of HIV-positive and HIV-negative patients were compared in all matched patients with pathological type of squamous cell carcinoma; the Kaplan-Meire method was used to analyze the overall survival (OS) and the comparison of OS was made by using log-rank test. Multivariate Cox proportional risk model was used to analyze the independent factors affecting the OS of patients with cervical squamous cell carcinoma.Results:The differences in the age, pathological types, clinical staging between 46 HIV-positive patients and 587 HIV-negative patients were statistically significant (all P < 0.05). There were statistically significant differences in age and clinical staging between 46 HIV-positive squamous cell carcinoma patients and 504 HIV-negative squamous cell carcinoma patients (all P < 0.05). After 1∶5 matching, there were no statistically significant differences in the age, clinical staging between 46 patients with HIV-positive squamous cell carcinoma and 230 patients with HIV-negative squamous cell carcinoma. The OS of HIV-positive patients in the entire group,pathological type of squamous cell carcinoma or after pairing was worse than that of HIV-negative patients (all P < 0.001). The median OS time of HIV-positive patients was 63 months (95% CI 61-109 months), while the median OS time of HIV-negative patients was not reached (95% CI 165-178 months, 164-178 months, 143-173 months, respectively). Multivariate Cox regression analysis showed that clinical staging Ⅲ-Ⅳ was an independent risk factor for OS in patients with cervical squamous cell carcinoma (Ⅲ-Ⅳ vs. Ⅰ-Ⅱ: HR = 1.573, 95% CI 1.032-2.397, P = 0.035); HIV infection was an independent protective factor for OS (HIV-positive vs. HIV-negative: HR = 0.087, 95% CI 0.042-0.182, P < 0.001), indicating that HIV-positive patients had an advantage in OS compared to HIV-negative patients at the same age and clinical staging. Age was not an independent influencing factor for OS ( P > 0.05). Conclusions:The onset age of HIV-positive cervical cancer tends to be younger and the clinical staging is late when patients are diagnosed. HIV-positive patients have poor prognosis.

卡波西肉瘤(KS)是一种艾滋病(AIDS)相关的恶性肿瘤,与卡波西肉瘤相关疱疹病毒(KSHV)感染有关.KS是AIDS患者最常见的临床表现之一,是一种AIDS指征性疾病.联合抗反转录病毒治疗是首选治疗方案.局部治疗主要用于KS的局灶病变.全身治疗主要针对局部侵袭性和播散性卡波西肉瘤,推荐药物是阿霉素脂质体和紫杉醇脂质体.免疫治疗与靶向治疗目前尚处于发展阶段.

梅毒性直肠炎是由梅毒螺旋体引起的肠道疾病,一期、二期梅毒均可发生.由于梅毒螺旋体和HIV有相同的传播途径,所以二者常合并感染.梅毒性直肠炎缺乏特异性临床表现及影像学特征,容易误诊及漏诊.根据患者性行为史,临床表现及梅毒血清学、肠镜、病理检查可综合诊断.本文现对 1 例HIV阳性梅毒性直肠炎患者临床特征进行总结,并进行相关文献复习.

Purpose-Immunotherapy has revolutionized cancer therapy, becoming the standard of care for various malignancy treatments. Human immunodeficiency virus (HIV) patients, however, are an underserved group with limited access to clinical trials and cancer therapy. This study was to evaluate the safety and efficacy of programmed cell death 1 (PD - 1) inhibitors in patients with advanced cancer and HIV/acquired immunodeficiency syndrome (AIDS). Methods and Materials-We performed a prospective, open-label, nonrandomized, phase 1 single center study. Patients with advanced cancer and HIV/AIDS received the treatment of PD - 1 inhibitors (camrelizumab, 200 mg, administered intravenously every 3 weeks), along with combination antiretroviral therapy (cART) for HIV. Results-Sixteen participants (12 men and 4 women; median age, 46.5 (29 - 78) years) were enrolled; 1 had non - Hodgkin lymphoma (NHL), and 15 had non - AIDS - defining cancers. Safety was observed over 130 cycles of treatment with camrelizumab. Most treatment-emergent adverse events at least possibly attributed to camrelizumab were grade 1 or 2, including reactive cutaneous capillary endothelial proliferation (RCCEP) (9 participants), hearing loss (1 participant), hypophysitis (1 participant). 3 participants experienced hemorrhage due to poor performance status. HIV was controlled in all participants. Best tumor responses included 3 complete response, 5 partial response, 2 stable disease, and 6 progressive disease. The 2 years progression-free survival (PFS) was 67.0% (95% CI: -0.05, 0.00) and overall survival (OS) was 55.3% (95% CI: -0.05, 0.01) for the 16 patients who had received camrelizumab. Conclusions-This study demonstrates that camrelizumab treatment in patients with advanced cancers and HIV/AIDS was feasible and the clinical outcomes were acceptable.

Objective:To investigate the pathogen spectrum of acquired immunodeficiency syndrome (AIDS) patients with pulmonary opportunistic infections in the local area, and to evaluate the clinical application of metagenomic next-generation sequencing (mNGS) in these patients.Methods:From January to December 2021, AIDS patients with pulmonary infections admitted to Zhongnan Hospital of Wuhan University were enrolled. Their bronchoalveolar lavage fluid (BALF) was subjected to mNGS and coventional pathogen detection.Routine pathogen detection methods included smear, culture, polymerase chain reaction (PCR), and immunochromatographic colloidal gold. Fisher′s exact probability method was used for statistical analysis.Results:A total of 69 patients were included, and all of them were tested positive for mNGS. Among them, 53 cases (76.8%) were positive for fungi and viruses, 40 cases (58.0%) were positive for bacteria (excluding Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM)), six cases were positive for MTB, 11 cases were positive for NTM, and seven cases were positive for other pathogens. Mixed infections with two or more pathogens were found in 89.9%(62/69) of the patients. Among the conventional pathogen detections of BALF, 79.7%(55/69) of the patients were positive for pathogens, including 42 cases positive for Pneumocystis jirovecii PCR, 16 cases positive for BALF culture, nine cases positive for MTB PCR, and five cases positive for Cryptococcus antigen. The total detection rate of mNGS was 100.0%(69/69), which was higher than that of the conventional pathogen detection rate of 79.7%(55/69), and the difference was statistically significant (Fisher′s exact probability method, P<0.001). The specificity of mNGS detection was 88.4%. Combining clinical and two detection methods, the top five pathogens were Pneumocystis jirovecii (62.3%(43/69)), Candida (29.0%(20/69)), MTB (20.3%(14/69)), NTM and Talaromyces marneffei (15.9%(11/69), each). Fifty-three patients (76.8%) had co-infection with virus. Conclusions:The main cause of pulmonary infection in AIDS patients in this area is mixed infection, and Pneumocystis jirovecii is the most common pathogen. mNGS could significantly improve the pathogen detection rate in AIDS patients with pulmonary infections.

To establish a plasma model to predict the risk of liver fibrosis in HIV/HBV co-infected individuals. Quantitative liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to identify differentially expressed proteins (DEPs) in plasma collected from HIV/HBV co-infected individuals with and without liver fibrosis. In total, 97 DEPs were identified, among which 11 were further validated as potential biomarkers, with immunoglobulin and complement components being the most common proteins. These markedly altered proteins were found to mediate pathophysiological pathways, including humoral immune response, complement and coagulation cascades, and complement activation. A visual logistic model, in which immunoglobulin heavy variable 3-20 (IGHV3-20), immunoglobulin heavy variable 1-24 (IGHV1-24), and macrophage colony-stimulating factor 1 receptor (CSF1R) proteins were included, has been established to predict liver fibrosis in HIV/HBV co-infected individuals. The preliminary conclusion showed that the combination of IGHV3-20, IGFHV1-24, and CSF1R is expected to become a predictive model for liver fibrosis in the context of HIV/HBV co-infection and a further validation should be performed.