CAR-T Cell Therapy: Advances in Kidney-Related Diseases.

Background: Chimeric antigen receptor (CAR)-T cell therapy represents a significant advancement in the field of immunotherapy, providing targeted eradication of abnormal cells through the recognition between CAR and target antigens. This approach has garnered considerable attention due to its promising results in the clinical treatment of hematological malignancies and autoimmune diseases. As the focus shifts toward exploring novel targets and expanding the application of CAR-T cell therapy to solid tumors, including renal malignancies, researchers are pushing the boundaries of this innovative treatment. However, it is crucial to address the observed comorbidities associated with CAR-T cell therapy, particularly nephrotoxicity, due to the superseding release of cytokines and impairment of normal tissue. Summary: Our review discusses the research strategies and nephrotoxicity related to CAR-T cell therapy in various kidney-related diseases and provides insights into enhancing investigation and optimization. Key Messages: CAR-T cell therapy has captured the attention of researchers and clinicians in the treatment of renal malignancies, multiple myeloma, systemic lupus erythematosus, and acquired immunodeficiency syndrome, which may lead to potential nephrotoxicity as they involve primary or secondary kidney complications. Understanding and summarizing the current research progress of CAR-T cell therapies can provide valuable insights into novel targets and combinations to optimize research models and enhance their clinical value.

Impact of Metabolic Syndrome and Cardiovascular Risk on the Quality of Life of People Living with HIV.

BACKGROUND: The time elapsed since HIV infection diagnosis (TdiagHIV) affects the quality of life (QoL) and can get worse when chronic illnesses start. OBJECTIVE: The aim of this study was to analyze the impact of metabolic syndrome (MetS) and cardiovascular risk (CVR) on the QoL of people living with HIV (PLHIV). METHODS: Cross-sectional study, with 60 PLHIV followed at a Reference Center in the city of Jataí, Goiás, Brazil. Data collection involved sociodemographic, clinical, CVR, MetS, and QoL information. The data were analyzed using descriptive and inferential statistics, with the BioEstat 5.3 program adopting p0.05. RESULTS: There was a predominance of men (61.7%), aged ≥38 years (53.3%), with a TdiagHIV of 97.88Añ85.65 months and use of antiretroviral therapy (ART) of 80.13Añ69.37 months. The worst domain of QoL was concern about confidentiality (40 points), and the best was medication concerns (95 points). MetS predominated at 18.3% and a moderate CVR at 11.7%. MetS was positively associated with age 38 years, the female sex, with the lowest score in QoL for general function, and the highest for TdiagHIV and the use of ART (p0.05). A moderate CRV was positively related to higher TdiagHIV and ART use, and low HDL-c, and the lowest score for QoL was found for trust in a professional (p0.05). CONCLUSION: PLHIV who are older, have a higher TdiagHIV, and use ART are more likely to develop MetS and moderate CVR. The presence of these diseases in PLHIV causes impairment in areas of QoL.

Impact of HIV status on prognosis of malignancies among people living with HIV in Japan.

BACKGROUND: Antiretroviral therapy has reduced the incidence and mortality of AIDS-defining malignancies (ADM); however, non-AIDS-defining malignancies (NADM) are a major cause of death among people living with HIV (PLWH) today. Though current guidelines suggest that PLWH should receive the same treatment as the general population, there are limited studies focused on how HIV status affects the prognosis of cancers. The present study aimed to investigate the characteristics and prognosis of malignant diseases among PLWH in Japan. METHODS: Patients with HIV diagnosed with malignant diseases at our institution between 2011 and 2021 were retrospectively reviewed. RESULTS: There were 205 patients who were diagnosed with malignancies. Of these, 87 (42.4%) were diagnosed with ADM and 118 (57.6%) were diagnosed with NADM. Among 69 patients who received chemotherapy for ADM, 24 (34.8%) developed AIDS-defining opportunistic infections during treatment. In contrast, only one (1.8%) of the 56 patients administered chemotherapy for NADM developed AIDS-defining opportunistic infections. Complications of opportunistic infections at diagnosis of malignancies, low CD4+ T-cell count, positive HIV RNA, and nonadministration of antiretroviral therapy were associated with 5-year overall survival among patients with malignant lymphomas. However, the variables associated with HIV did not affect NADM prognosis. CONCLUSIONS: In this analysis, HIV status had a small impact on the prognosis of malignant diseases in PLWH. Few patients with NADM developed AIDS-defining opportunistic infections after receiving chemotherapy.

Experiences of patients living with HIV and AIDS on antiretroviral therapy in Accra, Ghana.

BACKGROUND:  The human immunodeficiency virus and acquired immunodeficiency syndrome (HIV and AIDS) pandemic has greatly affected Africa, particularly Ghana. The pandemic remains a public health concern, particularly in terms of accessing essential medication and improving quality of life for people living with the disease. OBJECTIVES:  This study aimed to explore and describe the experiences of persons diagnosed and living with HIV who are on antiretroviral therapy. METHOD:  A qualitative, exploratory, descriptive, and contextual design was used. The research population included persons diagnosed with HIV who were receiving antiretroviral therapy at three public hospitals in Ghana. Data saturation was achieved after conducting 15 semi-structured interviews. Creswell's six steps of data analysis were used to analyse the data, which resulted in the emergence of one main theme and six sub-themes. RESULTS:  The main theme identified by the researchers highlighted the participants' diverse experiences of being diagnosed and living with HIV. It was found that the study participants expressed shock, disbelief, surprise, and fear of death after being diagnosed with HIV. The participants also experienced stigmatisation, discrimination, and rejection. CONCLUSION:  There is a need for further research on the extent of discrimination and stigmatisation and the effect on optimal adherence to antiretroviral therapy. Continuous public education on HIV is required to limit the extent of discrimination and stigmatisation.Contribution: The study has highlighted the various emotions related to stigma and discrimination expressed by persons living with HIV (PLHIV). The findings will guide policy on eliminating discrimination and stigmatisation for people living with HIV.

Comment on 'Changing relationships between HIV prevalence and circumcision in Lesotho', and 'Age-incidence and prevalence of HIV among intact and circumcised men: an analysis of PHIA surveys in Southern Africa'.

Two articles by Garenne (2023a,b) argue that voluntary medical male circumcision does not reduce human immunodeficiency virus transmission in Africa. Here we point out key evidence and analytical flaws that call into question this conclusion.

Defining the Effects of PKC Modulator HIV Latency-Reversing Agents on Natural Killer Cells.

Background: Latency reversing agents (LRAs) such as protein kinase C (PKC) modulators can reduce rebound-competent HIV reservoirs in small animal models. Furthermore, administration of natural killer (NK) cells following LRA treatment improves this reservoir reduction. It is currently unknown why the combination of a PKC modulator and NK cells is so potent and whether exposure to PKC modulators may augment NK cell function in some way. Methods: Primary human NK cells were treated with PKC modulators (bryostatin-1, prostratin, or the designed, synthetic bryostatin-1 analog SUW133), and evaluated by examining expression of activation markers by flow cytometry, analyzing transcriptomic profiles by RNA sequencing, measuring cytotoxicity by co-culturing with K562 cells, assessing cytokine production by Luminex assay, and examining the ability of cytokines and secreted factors to independently reverse HIV latency by co-culturing with Jurkat-Latency (J-Lat) cells. Results: PKC modulators increased expression of proteins involved in NK cell activation. Transcriptomic profiles from PKC-treated NK cells displayed signatures of cellular activation and enrichment of genes associated with the NFκB pathway. NK cell cytotoxicity was unaffected by prostratin but significantly decreased by bryostatin-1 and SUW133. Cytokines from PKC-stimulated NK cells did not induce latency reversal in J-Lat cell lines. Conclusions: Although PKC modulators have some significant effects on NK cells, their contribution in "kick and kill" strategies is likely due to upregulating HIV expression in CD4+ T cells, not directly enhancing the effector functions of NK cells. This suggests that PKC modulators are primarily augmenting the "kick" rather than the "kill" arm of this HIV cure approach.

Expression and prognostic significance of the PD-1/PD-L1 pathway in AIDS-related non-Hodgkin lymphoma.

OBJECTIVE: Immune tolerance and evasion play a critical role in virus-driven malignancies. However, the phenotype and clinical significance of programmed cell death 1 (PD-1) and its ligands, PD-L1 and PD-L2, in aggressive acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (AR-NHL) remain poorly understood, particularly in the Epstein-Barr virus (EBV)-positive subset. METHODS: We used in situ hybridization with EBV-encoded RNA (EBER) to assess the EBV status. We performed immunohistochemistry and flow cytometry analysis to evaluate components of the PD-1/PD-L1/L2 pathway in a multi-institutional cohort of 58 patients with AR-NHL and compared EBV-positive and EBV-negative cases. RESULTS: The prevalence of EBV+ in AR-NHL was 56.9% and was associated with a marked increase in the expression of PD-1/PD-L1/PD-L2 in malignant cells. Patients with AR-NHLs who tested positive for both EBER and PD-1 exhibited lower survival rates compared to those negative for these markers (47.4% vs. 93.8%, p = 0.004). Similarly, patients positive for both EBER and PD-L1 also demonstrated poorer survival (56.5% vs. 93.8%, p = 0.043). Importantly, PD-1 tissue-expression demonstrated independent prognostic significance for overall survival in multivariate analysis and was correlated to elevated levels of LDH (r = 0.313, p = 0.031), increased PD-1+ Tregs (p = 0.006), and robust expression of EBER (r = 0.541, p < 0.001) and PD-L1 (r = 0.354, p = 0.014) expression. CONCLUSIONS: These data emphasize the importance of PD-1-mediated immune evasion in the complex landscape of immune oncology in AR-NHL co-infected with EBV, and contribute to the diagnostic classification and possible definition of immunotherapeutic strategies for this unique subgroup.

[Bad luck or a common reality? Multiple exposures a nurse to potentially infectious material: a case report]. / Pech czy powszechna rzeczywistosc? Liczne ekspozycje pielegniarki na material potencjalnie zakazny: opis przypadku.

Presented is the case of a nurse who had 4 occupational exposures to potentially infectious material between December 2020 and June 2022. In 2 of the cases, the source patient was unknown, so pharmacological HIV post-exposure prophylaxis was implemented (in 1 of these cases, the nurse developed weakness and increased dyspeptic symptoms, necessitating a change in the antiretroviral medications used). During the interview collection, the nurse reported that multiple exposures to potentially infectious material are common in her work environment, but most of these are not reported. This is supported by the results of several studies devoted to the problem of non-reporting of occupational exposures by health care workers. However, there is significant discrepancy in the results of these studies, which may be due to different methods. The authors of this article believe that after 10 years since the entry into force of the regulation of the Minister of Health standardizing procedures for dealing with injuries caused by sharp instruments used in the provision of health care services, a serious problem remains of non-reporting of cases by employees (resulting in a lack of post-exposure prophylaxis). The authors call for the introduction of a nationwide reporting system. There is also a need to increase the importance of prophylaxis of stabbings and to improve the quality of training of medical personnel in post-exposure prophylaxis procedures. Med Pr Work Health Saf. 2024;75(2):173-179.

Exploring Stigma Experience and Coping Strategies Among Women Living with HIV/AIDS in China: A Phenomenological Study.

Purpose: As of the end of 2022, over 20 million women worldwide, aged 15 and above, are living with HIV. Stigma remains a formidable barrier for women living with HIV/AIDS, hindering their access to healthcare and exacerbating health disparities. Indeed, some women living with HIV/AIDS can successfully confront and overcome stigma. There remains a paucity of qualitative research exploring the stigma coping strategies of women living with HIV/AIDS in China. This study was aimed to gain the deeper understanding of stigma experienced by women living with HIV/AIDS and coping strategies. Patients and Methods: We recruited diverse participants using snowball sampling and purposive sampling. Semi-structured personal in-depth interviews were conducted with 30 women living with HIV/AIDS from December 2022 to June 2023. The samples were from four HIV/AIDS designated hospitals. The data were analyzed using the Colaizzi seven-step model. Results: The experiences of stigma among women living with HIV/AIDS included family role (wife/mother/grandmother) collapse and disgusted by family, resignation in being shunned by others, helplessness due to social exclusion, grief at being devaluated, and resentment for experiencing injustice. The coping strategies used to deal with stigma included concealing their conditions, avoiding socialization, and attempting to retaliate against society. Conclusion: Healthcare professionals are recommended to offer women living with HIV/AIDS effective emotional support and guidance to cope with stigma. The study highlights the stigma they face, providing valuable evidence for policymakers. Recommendations emphasize the importance of developing services addressing both physical and psychological needs of women living with HIV/AIDS.

Toxoplasmic encephalitis with high 201Tl uptake and retention mimicking malignant lymphoma in a patient with human immunodeficiency virus infection.

Various opportunistic infections develop during immunodeficiency due to human immunodeficiency virus (HIV) infection. The treatment options for malignant lymphoma (ML) and toxoplasmic encephalitis (TE) are completely different; therefore, their discrimination is critical. A 25-year-old female of foreign nationality had been experiencing headaches for several weeks and suddenly developed convulsions. Brain computed tomography revealed multiple intracranial lesions; therefore, the patient was referred to the neurosurgery department. Brain magnetic resonance imaging (MRI) revealed multiple masses with surrounding edema, accompanied by enhanced contrast. The largest mass (2 cm) in the left occipital lobe exhibited ringed contrast enhancement. Her blood test results showed a CD4 count of 40/µL, positive HIV Ag/Ab, HIV-RNA level of 56 × 104 copies/mL, positive anti-Toxoplasma IgG (63 IU/mL), and negative anti-Toxoplasma IgM. 201Tl- single photon emission computed tomography (201Tl-SPECT) revealed abnormal accumulation only in the tumor in the left occipital lobe (early T/N ratio, 3.034; delayed T/N ratio, 2.738; retention index, 0.9), which was suspected to be a ML. Both tumors, with or without high accumulation of 201Tl, were subjected to craniotomy biopsy. Pathological examination revealed infiltration of small lymphocytes with a necrotic background. The patient was diagnosed with TE based on a positive result of a tissue polymerase chain reaction test for Toxoplasma gondii. Two weeks after sulfamethoxazole and trimethoprim combination therapy, MRI imaging showed dramatic improvement in multiple brain tumors. This case is atypical because ML was ruled out despite high 201Tl-SPECT uptake and retention. Careful diagnosis through pathological examination and DNA testing is important.

Peer interventions to improve HIV testing uptake among immigrants: A realist review.

Background: As a vulnerable group in HIV control programs, immigrants face various obstacles to HIV testing. Despite the effectiveness of peer interventions on health promotion in HIV testing, relatively little is known about how these interventions work. This realist review aims to understand why, how, and under what conditions peer interventions can improve immigrants' HIV testing uptake. Methods: We followed the steps suggested by Pawson and colleagues for conducting the realist review. To test a initial program theory, we first systematically searched databases of PubMed, Web of Science, Scopus, Embase, and Cochrane, as well as the websites of UNAIDS, World Bank, Global Fund, WHO, and IOM. After data extraction and quality appraisal, data synthesis was conducted to explain the intervention pathways corresponding to context-mechanism-outcome configurations. Results: Seventeen studies were included in the review. Peer interventions for improving immigrants' HIV testing uptake worked through four pathways: Following the improvement of communications (as a proximal mechanism): 1) increasing awareness, 2) reduced stigma, 3) improved support, and 4) increased access to services could lead to improved HIV testing uptake among immigrants. The identified mechanisms were influenced by three groups of individual/ interpersonal, service delivery, and structural factors. Conclusion: Peer interventions with multiple strategies to be designed and implemented considering the barriers to HIV testing and also moving beyond one-size-fits-all approaches can successfully improve the immigrants' HIV testing uptake. The refined program theory in this study can help the healthcare providers and policy-makers promote the immigrants' HIV testing uptake and reduce the risk of disease transmission.

Enhancing indicator condition-guided HIV testing in Taiwan: a nationwide case-control study from 2009 to 2015.

BACKGROUND: Although indicator condition (IC)-guided HIV testing (IC-HIVT) is effective at facilitating timely HIV diagnosis, research on IC categories and the related HIV risk in Taiwan is limited. To improve the adoption and spread of IC-HIVT in Taiwan, this study compared the IC categories of people living with HIV (PLWH) and non-HIV controls and investigated delays in the diagnosis of HIV infection. METHODS: This nationwide, retrospective, 1:10-matched case-control study analyzed data from the Notifiable Diseases Surveillance System and National Health Insurance Research Database to evaluate 42 ICs for the 5-year period preceding a matched HIV diagnostic date from 2009 to 2015. The ICs were divided into category 1 ICs (AIDS-defining opportunistic illnesses [AOIs]), category 2 ICs (diseases associated with impaired immunity or malignancy but not AOIs), category 3 ICs (ICs associated with sexual behaviors), and category 4 ICs (mononucleosis or mononucleosis-like syndrome). Logistic regression was used to evaluate the HIV risk associated with each IC category (at the overall and annual levels) before the index date. Wilcoxon rank-sum test was performed to assess changes in diagnostic delays following an incident IC category by HIV transmission routes. RESULTS: Fourteen thousand three hundred forty-seven PLWH were matched with 143,470 non-HIV controls. The prevalence results for all ICs and category 1-4 ICs were, respectively, 42.59%, 11.16%, 15.68%, 26.48%, and 0.97% among PLWH and 8.73%, 1.05%, 4.53%, 3.69%, and 0.02% among non-HIV controls (all P < 0.001). Each IC category posed a significantly higher risk of HIV infection overall and annually. The median (interquartile range) potential delay in HIV diagnosis was 15 (7-44), 324.5 (36-947), 234 (13-976), and 74 (33-476) days for category 1-4 ICs, respectively. Except for category 1 for men who have sex with men, these values remained stable across 2009-2015, regardless of the HIV transmission route. CONCLUSIONS: Given the ongoing HIV diagnostic delay, IC-HIVT should be upgraded and adapted to each IC category to enhance early HIV diagnosis.

Prevalence of Selected Cardiovascular Risk Factors and Their Associated Factors among People Living with HIV/AIDS in India.

Background: Low- and middle-income countries face the dual problem of infectious and non-infectious diseases. Persons living with HIV/AIDS (PLHIV) are also at risk of cardiovascular diseases. Hence, we did this study to determine the prevalence of cardiovascular risk factors (CVRF) among PLHIV and to find the factors associated with it. Methods: We carried out a cross-sectional analytical study among all adults aged ≥18 years registered at a facility-integrated anti-retroviral therapy center in Puducherry, India, from September 2016 to February 2018. After obtaining informed consent, we interviewed the participants to assess physical activity, alcohol, and tobacco use. We measured weight, height, abdominal circumference, and blood pressure, with biochemical investigations such as blood glucose and lipid profile. Results: Of the total 316 adults PLHIV studied, the most common cardiovascular risk factor found was dyslipidemia (82.7%), followed by inadequate physical activity (74.4%). Other behavioral risk factors studied, such as current tobacco use and current alcohol use, showed a prevalence of 12.8% and 5.4%, respectively, among male participants. The prevalence of hypertension among adult PLHIV studied was 15.8%, and diabetes was 12.3%. In the multivariate analysis, diabetes, and hypertension were significantly associated with age and literacy. Obesity was found to be associated with diabetes and abdominal obesity with dyslipidemia. Conclusion: Dyslipidemia was the most common cardiovascular risk factor, followed by inadequate physical inactivity among PLHIV. Regular screening with blood glucose, blood pressure, and lipid profile, and timely cross-referrals can help in the early detection of CVRF among PLHIV and hence improve their quality of life through appropriate treatment.

Psychometric properties of stigma and discrimination measurement tools for persons living with HIV: a systematic review using the COSMIN methodology.

BACKGROUND: The development of antiretroviral therapy broadly extends the life expectancy of persons living with HIV (PLHIV). However, stigma and discrimination are still great threat to these individuals and the world's public health care system. Accurate and reproducible measures are prerequisites for robust results. Therefore, it is essential to choose an acceptable measure with satisfactory psychometric properties to assess stigma and discrimination. There has been no systematic review of different stigma and discrimination tools in the field of HIV care. Researchers and clinical practitioners do not have a solid reference for selecting stigma and discrimination measurement tools. METHODS: We systematically searched English and Chinese databases, including PubMed, EMBASE, CINAHL, Web of Science, PsycINFO, ProQuest Dissertations and Theses, The Cochrane Library, CNKI,, and Wanfang, to obtain literature about stigma and discrimination measurement tools that have been developed and applied in the field of HIV. The search period was from 1st January, 1996 to 22nd November 2021. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline (2018 version) was applied to assess the risk of bias for each involved study and summarize the psychometric properties of each tool. The modified version of the Grading of Recommendations Assessment, Development, and, Evaluation (GRADE) method was used to grade the evidence and develop recommendations. RESULTS: We included 45 studies and 19 PROMs for HIV/AIDS-related stigma and discrimination among PLHIV. All studies had sufficient methodological quality in content validity, structural validity, internal consistency, and the hypothesis testing of structural validity. Limited evidence was found for cross-cultural validity, stability, and criterion validity. No relevant evidence was found concerning measurement error and responsiveness. The Internalized AIDS-related Stigma Scale (IARSS), Internalized HIV Stigma Scale (IHSS), and Wright's HIV stigma scale (WHSS) are recommended for use. CONCLUSIONS: This study recommends three PROMs for different stigma and discrimination scenarios, including IARSS for its good quality and convenience, IHSS for its broader range of items, higher sensitivity, and greater precision, and WHSS for its comprehensive and quick screening. Researchers should also consider the relevance and feasibility of the measurements before putting them into practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022308579.

Multiple carcinomas in a woman with HIV infection: a case report and literature review.

Non-acquired immunodeficiency syndrome-defining cancers (NADCs) are malignancies in persons living with human immunodeficiency virus (PLWHIV) and are not primarily due to the host's immunodeficiency. There is renewed clinical interest in long-term morbidities in PLWHIV as well as malignancies that occur in this population. We herein describe a 36-year-old woman with a 2-year history of an anal wound and right breast mass. She had been diagnosed with HIV infection prior to the development of these lesions. Clinical and laboratory evaluations led to diagnoses of breast and anal cancers. Chemotherapy and antiretroviral therapy were begun, but the patient discontinued these treatments early and was lost to follow-up. NADCs will continue to be a major clinical issue as the global population ages. This presentation of two NADCs (breast and anal cancers) in a PLWHIV further highlights the burden of multiple malignancies on the depleted health of HIV-infected patients. Early identification and treatment of HIV upon patients' presentation to cancer care sites and screening for NADCs at HIV/AIDS care sites are recommended for improved outcomes.

Effectiveness of human immunodeficiency virus prevention strategies by mapping the geographic dispersion pattern of human immunodeficiency virus prevalence in Nanning, China.

BACKGROUND: The Guangxi government initiated two rounds of the Guangxi AIDS Conquering Project (GACP) in 2010 (Phase I) and 2015 (Phase II) to control human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemics. However, the effectiveness of GACP in HIV prevention and treatment has rarely been reported. This study aimed to assess the effectiveness of the GACP implemented in Guangxi, China and provide data for strategy and praxis improvements to achieve Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95 targets. METHODS: We used spatial approaches to trace the spatiotemporal distribution properties, epidemic trends, and correlation between macroscopic factors and HIV incidence using data from the Chinese HIV/AIDS case reporting system to explore the effects of the GACP. RESULTS: During the GACP era, the HIV epidemic stabilized in urban centers, showing a downward trend in the Hengzhou and Binyang Counties in the eastern region, whereas it continued to increase in rural areas of the northwest region, such as the Long'an, Mashan, Shanglin, and Wuming Districts. The linear directional mean (LDM) of HIV infection reported cases displayed a southeast-northwest direction, with an LDM value of 12.52°. Compared with that in Phase I, Hengzhou withdrew from the high-high clustering area, and the west-north suburban counties pulled out the low-low clustering area during Phase II. Significant HIV clusters were identified in the eastern region during Phase I, whereas these clusters emerged in the northwestern areas during Phase II. Regarding HIV, socioeconomic status, population mobility, and medical care levels were the key social drivers of heterogeneous spatial distribution. CONCLUSIONS: The GACP assisted in effectively managing the HIV epidemic in urban and eastern areas of Nanning City. However, prevention and control efforts in rural regions, particularly those located in the northwest, may not have yielded comparable outcomes. To address this disparity, allocating additional resources and implementing tailored intervention measures for these rural areas are imperative.

Genetic factors associated with age-related macular degeneration modulating plasma inflammatory biomarker levels in patients with AIDS.

INTRODUCTION: Patients with the acquired immunodeficiency syndrome (AIDS) have an increased prevalence and incidence of intermediate-stage age-related macular degeneration (AMD). Several elevated plasma inflammatory biomarkers are associated with increased incidence of intermediate-stage AMD in this population. We evaluated the association between AMD risk alleles and plasma inflammatory biomarker levels in persons with AIDS. MATERIALS AND METHODS: Cryopreserved plasma specimens of 229 non-Hispanic White and 252 non-Hispanic blacks from the Longitudinal Study of the Ocular Complications of AIDS cohort were assayed for plasma levels of soluble tumor necrosis factor receptor (sTNFR) 2, interleukin (IL)-18, C × 3motif chemokine ligand 1 (CX3CL1), C-reactive protein (CRP), and soluble CD14 (sCD14). Genotyping included AMD-associated variants rs10801553 and rs800292 for complement factor H (CFH) rs9332739 and rs547154 for complement factor 2 (C2), rs2230199 for C3, rs2285714 for CFI, and rs3732379 and rs3732378 for C × 3motif chemokine receptor 1 (CX3CR1). RESULTS: In Whites, AMD low-risk CX3CR1 variants (V249I and T280M) were associated with reduced plasma levels of IL-18. In Blacks, AMD low-risk C3 R102G and low-risk CX3CR1 T280M variants were associated with reduced CRP levels. CONCLUSIONS: Genetic variants in AMD-associated immune genes may influence AMD-associated systemic plasma inflammatory biomarker levels in patients with AIDS.

Exploring the experiences of peer support participation for HIV peer volunteers: A meta-synthesis of qualitative research.

BACKGROUND: Gaining insights and feedback from HIV peer volunteers about their peer support practice is crucial for optimizing and enhancing the effectiveness and sustainability of peer support for people with HIV. There is a dearth of systematic reviews that explore the experiences of HIV peer volunteers about their peer support experience. This study aims to consolidate qualitative research on the experiences of peer support participation for HIV peer volunteers, to provide inspiration and reference for HIV peer support practice. METHODS: A meta-aggregation approach was employed to synthesize qualitative studies. Electronic databases were searched for peer-reviewed and gray literature published in English and Chinese between 1996 and September 2022. Two independent reviewers assessed the methodological quality and extracted data from the included studies. The meta-aggregation approach developed by the Joanna Briggs Institute (JBI) was utilized to synthesize the findings. RESULTS: A total of 2610 studies were initially identified through the database search, and twenty-two eligible studies were included in the meta-synthesis. Among the included studies, five presented synthesized findings on the following topics: firstly, taking people with HIV as HIV peer volunteers shows specific motivations and advantages when engaging in peer support practice. Secondly, HIV peer volunteers reinforce the connections between people with HIV and medical institutions, ensuring continuity of care and compensating for the limited availability of medical resources. Thirdly, HIV peer volunteers are capable of providing people with HIV with a higher level of support. Additionally, participating in peer support practice can also yield personal benefits for HIV peer volunteers. Finally, HIV peer support programs face both opportunities and challenges. CONCLUSION: It is necessary to take more flexible and effective approaches to address resource allocation and social support for people with HIV. Peer support presents a mutually beneficial option that holds significant implications for public health systems, clinical healthcare providers, people with HIV, and HIV peer volunteers. It is imperative to develop effective models for HIV peer support practice. Collaborative efforts between relevant departments and personnel, alongside HIV peer volunteers, should be undertaken to formulate support strategies. Additionally, efforts should be made to identify and guide people with HIV into the healthcare system, facilitating comprehensive treatment and care continuity. These measures aim to further reduce HIV transmission, improve the quality of life for people with HIV, and advance the "normalization" of HIV.

The ecto-enzyme CD38 modulates CD4 T cell immunometabolic responses and participates in HIV pathogenesis.

Despite abundant evidence correlating T cell CD38 expression and HIV infection pathogenesis, its role as a CD4 T cell immunometabolic regulator remains unclear. We find that CD38's extracellular glycohydrolase activity restricts metabolic reprogramming after TCR-engaging stimulation in Jurkat T CD4 cells, together with functional responses, while reducing intracellular NAD and NMN concentrations. Selective elimination of CD38's ectoenzyme function licenses them to decrease the OCR/ECAR ratio upon TCR signaling and to increase cycling, proliferation, survival, and CD40L induction. Pharmacological inhibition of ectoCD38 catalytic activity in memory CD4 T cells from chronic HIV-infected patients rescued TCR-triggered responses, including differentiation and effector functions, while reverting abnormally increased basal glycolysis, cycling, and spontaneous pro-inflammatory cytokine production. Additionally, ecto-CD38 blockage normalized basal and TCR-induced mitochondrial morpho-functionality, while increasing respiratory capacity in cells from HIV+ patients and healthy individuals. Ectoenzyme CD38's immunometabolic restriction of TCR-involving stimulation is relevant to CD4 T cell biology and to the deleterious effects of CD38 overexpression in HIV disease.

Characteristics of Hepatitis B Virus, Hepatitis C Virus, and Syphilis Coinfection in People With HIV/AIDS Contracted Through Different Sources: Retrospective Study.

BACKGROUND: The burden of hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis coinfections remains disproportionately high among people living with HIV/AIDS. Hubei province is located in central China, where there are distinct regional characteristics of the distribution of people living with HIV/AIDS acquired via diverse transmission routes and the AIDS epidemic itself. OBJECTIVE: We aimed to estimate the magnitude of HBV, HCV, or syphilis coinfections among people living with HIV/AIDS with blood-borne transmission, which includes former paid blood donors, contaminated blood recipients, and intravenous drug users, as well as among people with sex-borne HIV transmission (including heterosexual people and men who have sex with men) and people with mother-to-child HIV transmission. METHODS: From January 2010 to December 2020, people living with HIV/AIDS were tested for hepatitis B surface antigen (HBsAg), HCV antibodies, and syphilis-specific antibodies. The positive patients were further tested for HBV markers, HBV DNA, and HCV RNA, and received a rapid plasma reagin circle card test. All people living with HIV/AIDS were first divided into transmission groups (blood, sex, and mother-to-child); then, people with blood-borne HIV transmission were divided into former paid blood donors, contaminated blood recipients, and intravenous drug users, while people with sex-borne HIV transmission were divided into heterosexual people and men who have sex with men. RESULTS: Among 6623 people living with HIV/AIDS, rates of chronic HCV infection were 80.3% (590/735) in former paid blood donors, 73.3% (247/337) in intravenous drug users, 57.1% (444/777) in contaminated blood recipients, 19.4% (21/108) in people with mother-to-child HIV transmission, 8.1% (240/2975) in heterosexual people, and 1.2% (21/1691) in men who have sex with men. Chronic HBV infection rates were similar among all people with blood-borne HIV transmission. However, compared to heterosexual people, the chronic HBV infection rate was greater in men who have sex with men (213/1691, 12.6% vs 308/2975, 10.4%; χ21=5.469; P=.02), although HBV exposure was less common (827/1691, 48.9% vs 1662/2975, 55.9%; χ21=20.982; P<.001). Interestingly, the combination of HBsAg and hepatitis B e antigen (HBeAg) was found in 11 patients with sex-borne HIV transmission, but in 0 people with blood-borne HIV transmission (11/196, 5.6% vs 0/521, 0%; χ21=29.695, P<.001). In people with sex-borne HIV transmission, the proportions of patients with a syphilis titer ≥1:16 and neurosyphilis were 8.6% (105/1227) and 7.8% (37/473), respectively, whereas these values were 0 in people with blood-borne HIV transmission. CONCLUSIONS: In people living with HIV/AIDS, HCV transmission intensity was significantly associated with specific exposure modes of blood or sexual contact. The rate of chronic HBV infection among men who have sex with men was higher than in any other population. Attention should be paid to the high prevalence of neurosyphilis in people living with HIV/AIDS who contract HIV by sexual intercourse.