Peer-Led Community-Based Support Services and HIV Treatment Outcomes Among People Living With HIV in Wuxi, China: Propensity Score-Matched Analysis of Surveillance Data From 2006 to 2021.

BACKGROUND: Community-based organizations deliver peer-led support services to people living with HIV. Systematic reviews have found that peer-led community-based support services can improve HIV treatment outcomes; however, few studies have been implemented to evaluate its impact on mortality using long-term follow-up data. OBJECTIVE: We aimed to evaluate the associations between the receipt of peer-led community-based support services and HIV treatment outcomes and survival among people living with HIV in Wuxi, China. METHODS: We performed a propensity score-matched retrospective cohort study using data collected from the Chinese National HIV/AIDS Comprehensive Information Management System for people living with HIV in Wuxi, China, between 2006 and 2021. People living with HIV who received adjunctive peer-led community-based support for at least 6 months from a local community-based organization (exposure group) were matched to people living with HIV who only received routine clinic-based HIV care (control group). We compared the differences in HIV treatment outcomes and survival between these 2 groups using Kaplan-Meier curves. We used competing risk and Cox proportional hazards models to assess correlates of AIDS-related mortality (ARM) and all-cause mortality. We reported adjusted subdistribution hazard ratio and adjusted hazard ratio with 95% CIs. RESULTS: A total of 860 people living with HIV were included (430 in the exposure group and 430 in the control group). The exposure group was more likely to adhere to antiretroviral therapy (ART; 396/430, 92.1% vs 360/430, 83.7%; P<.001), remain retained in care 12 months after ART initiation (402/430, 93.5% vs 327/430, 76.1%; P<.001), and achieve viral suppression 9 to 24 months after ART initiation (357/381, 93.7% vs 217/243, 89.3%; P=.048) than the control group. The exposure group had significantly lower ARM (1.8 vs 7.0 per 1000 person-years; P=.01) and all-cause mortality (2.3 vs 9.3 per 1000 person-years; P=.002) and significantly higher cumulative survival rates (P=.003). The exposure group had a 72% reduction in ARM (adjusted subdistribution hazard ratio 0.28, 95% CI 0.09-0.95) and a 70% reduction in all-cause mortality (adjusted hazard ratio 0.30, 95% CI 0.11-0.82). The nonrandomized retrospective nature of our analysis prevents us from determining whether peer-led community-based support caused the observed differences in HIV treatment outcomes and survival between the exposure and control groups. CONCLUSIONS: The receipt of peer-led community-based support services correlated with significantly improved HIV treatment outcomes and survival among people living with HIV in a middle-income country in Asia. The 15-year follow-up period in this study allowed us to identify associations with survival not previously reported in the literature. Future interventional trials are needed to confirm these findings.

Improved detection of EGFR mutations in the tumor cells enriched from the malignant pleural effusion of non-small cell lung cancer patient.

Previous studies focus on developing high sensitive PCR-related technologies to detect EGFR gene mutation in malignant pleural effusion (MPE) of non-small cell lung cancer patient (NSCLC) instead of improving the quality of clinical samples themselves. We therefore hypothesized that the enrichment of tumor cells in MPE could improve the quality of MPE for the more accurate detection of EGFR gene mutation in the patients with NSCLC. MPE were collected from 28 patients with NSCLC. The tumor cells in MPE were firstly enriched by the depletion of leukocytes with bi-antibodies and identified by multiple flow cytometry. CastPCR was performed to detect the deletions in exon 19 (DelEGFR19) and point mutations in 20 (T790M, c.2369C>T) and 21 (L858R, c.2573T>G) of EGFR. All the detected mutations were confirmed their presence by Sanger sequencing. Before enrichment, the tumor cells in MPE were detected in 46.4% (13/28) of samples and the median value of the percentage of the tumor cells was only 0.64% including 3 (10.7%, 3/28) of samples more than 10% on it. After enrichment, the tumor cells were detected in all samples (100%) and the median value of the percentage of tumor cells was increased to 40.8% including only one (3.6%, 1/28) less than 10% on it. EGFR gene mutations were detected in 28.6% (8/28) and 42.9% (12/28) of the samples before and after enrichment, respectively. The sensitivity on the detection rate was relatively increased by 44.4%. Moreover, the mutations can be confirmed their presence by Sanger sequencing in 6 samples before enrichment (75%, 6/8) and 11 samples (91.7%, 11/12) after enrichment. It is valuable to improve the quality of the sample by the enrichment of the tumor cells from MPE for the following genetic analysis.

Drug-resistant CXCR4-positive cells have the molecular characteristics of EMT in NSCLC.

High expression of Chemokine receptor 4 (CXCR4) is important in tumor invasion, metastasis, drug-resistance and maintenance of stemness in non-small cell lung cancer (NSCLC). We therefore studied the molecular characteristics of drug-resistant CXCR4-positive cells on epithelial-mesenchymal transition (EMT) for the future identification of the tumor cells with the properties of both EMT and stemness. EMT RT2 Profier PCR Array was performed to determine the expression levels of mRNA genes in A549 with TGF-ß1 induced EMT (A549/TGF-ß1) and gefitinib-resistant CXCR4-positive cells (A549/GR). TCGA database on the cBio Cancer Genomics Portal website and Gene Network Central (GNC) Pro Tutorial were used to analyze their clinical relevance and pathway interactions. CXCR4 was up-regulated both in TGF-ß induced EMT cells and in gefitinib-resistant cells. In 84 mRNA genes related to EMT, 17 mRNA genes were up-regulated in CXCR4-positive population of A549/GR when compared to those in CXCR4 negative fraction, while 66 mRNA genes were up-regulated during TGF-ß induced EMT. ITGA5, BMP7, MMP3, VIM, RGS2, ZEB2, TCF3, SNAI2, VCAN, PLEK2, WNT5A, COL3A1, SPARC and FOXC2 were doubly up-regulated during the two biological processes. Kaplan-Meier analysis indicated that the doubly up-regulated ITGA5, RGS2, SNAI2 and PLEK2 mRNA genes were related to poor overall survival in lung adenocarcinoma patients (P=9.291e-6, 0.0090, 3.81e-7 and 0.0013, respectively). In GNC analysis, SNAI2 mRNA gene but not ITGA5, RGS2 and PLEK2 was dependent on the signaling pathway of CXCR4. The molecular characteristics of drug-resistant CXCR4-positive cells have a crosstalk with EMT, which has the potential to find the marker with prognostic value on multiple signaling pathways in NSCLC.

Circulating Tumor Cells Enriched by the Depletion of Leukocytes with Bi-Antibodies in Non-Small Cell Lung Cancer: Potential Clinical Application.

BACKGROUND: It has been considered that the detection methods for circulating tumor cells (CTCs) based on epithelial cell adhesion molecule (EpCAM) underestimate the number of CTCs and may miss a metastatic subpopulation with cancer stem cell (CSC) properties. Therefore, we investigated EpCAM-positive and -negative CTCs in non-small cell lung cancer (NSCLC) patients at different stages, assessed the clinical value of these CTCs and explored their capacity in the following CSC model. METHODS: CTCs were enriched by the depletion of leukocytes with bi-antibodies using a magnetic bead separation technique and then identified by the expression of EpCAM and cytokeratin 7 and 8 using multi-parameter flow cytometry. We determined the distribution of CTCs classified by the expression of EpCAM in 46 NSCLC patients with stages I to IV, assessed the diagnostic value of these CTCs by longitudinal monitoring in 4 index patients during adjuvant therapy and characterized the stemness of these CTCs by the expression of CXCR4 and CD133 in 10 patients. RESULTS: EpCAM-negative (E-) CTCs were detected to be significantly higher than EpCAM-positive (E+) CTCs in stage IV (p = 0.003). The patients with the percentage of E-CTCs more than 95% (r > 95%) were detected to be significantly increased from 13.3% in stage I-II to 61.1% in stage IV (p = 0.006). Kaplan-Meier analysis indicated that the patients with r > 95% had significantly shorter survival time than those with r ≤ 0.95 (p = 0.041). Longitudinal monitoring of CTCs indicated that the patients with a high percentage of E-CTCs in the blood were not responsive to either chemotherapy or targeted therapy. Further characterization of CTCs revealed that a stem-like subpopulation of CXCR4+CD133+ CTCs were detected to be significantly more prevalent in E-CTCs than that in E+CTCs (p = 0.005). CONCLUSIONS: The enrichment of CTCs by the depletion of leukocytes with bi-antibodies is a valuable method for estimating the number of CTCs, which can be potentially applied in predicting the prognosis, monitoring the therapeutic effect of NSCLC patients and further analyzing the biology of CTCs.