Highly active antiretroviral therapy (ART) can effectively inhibit virus replication and restore immune function in most people living with human immunodeficiency virus (HIV). However, an important proportion of patients fail to achieve a satisfactory increase in CD4+ T cell counts. This state is called incomplete immune reconstitution or immunological nonresponse (INR). Patients with INR have an increased risk of clinical progression and higher rates of mortality. Despite widespread attention to INR, the precise mechanisms remain unclear. In this review, we will discuss the alterations in the quantity and quality of CD4+ T as well as multiple immunocytes, changes in soluble molecules and cytokines, and their relationship with INR, aimed to provide cellular and molecular insights into incomplete immune reconstitution.

https://www.frontiersin.org/articles/10.3389/fimmu.2023.1152951/pdf

Cellular and molecular insights into incomplete immune recovery in HIV/AIDS patients

HPV-16-immortalized genital and oral epithelial cells and HPV-negative oral cancer cells that undergo prolonged contact with cell-free HIV-1 virions or with viral proteins gp120 and tat respond by becoming more invasive. EMT cells induced by HIV-1 in cultures of HPV-16-immortalized anal and cervical epithelial cells express the stem cell markers CD133 and CD44. ABSTRACT The incidence of human papillomavirus (HPV)-associated anogenital and oropharyngeal cancer in human immunodeficiency virus (HIV)-infected individuals is substantially higher than in HIV-uninfected individuals. HIV may also be a risk factor for the development of HPV-negative head and neck, liver, lung, and kidney cancer. However, the molecular mechanisms underlying HIV-1-associated increase of epithelial malignancies are not fully understood. Here, we showed that HPV-16-immortalized anal AKC-2 and cervical CaSki epithelial cells that undergo prolonged exposure to cell-free HIV-1 virions or HIV-1 viral proteins gp120 and tat respond with the epithelial-mesenchymal transition (EMT) and increased invasiveness. Similar responses were observed in HPV-16-infected SCC-47 and HPV-16-negative HSC-3 oral epithelial cancer cells that were cultured with these viral proteins. EMT induced by gp120 and tat led to detachment of poorly adherent cells from the culture substratum; these cells remained capable of reattachment, upon which they coexpressed both E-cadherin and vimentin, indicative of an intermediate stage of EMT. The reattached cells also expressed stem cell markers CD133 and CD44, which may play a critical role in cancer cell invasion and metastasis. Inhibition of transforming growth factor (TGF)-β1 and MAPK signaling and vimentin expression, and restoration of E-cadherin expression reduced HIV-induced EMT and the invasive activity of HPV-16-immortalized anal and cervical epithelial cells. Collectively, our results suggest that these approaches along with HIV viral suppression with antiretroviral therapy (ART) might be useful to limit the role of HIV-1 infection in the acceleration of HPV-associated or HPV-independent epithelial neoplasia. IMPORTANCE HPV-16-immortalized genital and oral epithelial cells and HPV-negative oral cancer cells that undergo prolonged contact with cell-free HIV-1 virions or with viral proteins gp120 and tat respond by becoming more invasive. EMT cells induced by HIV-1 in cultures of HPV-16-immortalized anal and cervical epithelial cells express the stem cell markers CD133 and CD44. These results suggest that the interaction of HIV-1 with neoplastic epithelial cells may lead to their de-differentiation into cancer stem cells that are resistant to apoptosis and anti-cancer drugs. Thus, this pathway may play a critical role in the development of invasive cancer. Inhibition of TGF-β1 and MAPK signaling and vimentin expression, and restoration of E-cadherin expression reduced HIV-induced EMT and the invasiveness of HPV-16-immortalized anal and cervical epithelial cells. Taken together, these results suggest that these approaches might be exploited to limit the role of HIV-1 infection in the acceleration of HPV-associated or HPV-independent epithelial neoplasia.

HIV-1 Proteins gp120 and Tat Promote Epithelial-Mesenchymal Transition and Invasiveness of HPV-Positive and HPV-Negative Neoplastic Genital and Oral Epithelial Cells

Antiretroviral therapy (ART) induces persistent suppression of HIV-1 replication and gradual recovery of T-cell counts, and consequently, morbidity and mortality from HIV-related illnesses have been significantly reduced. However, in approximately 30% of people living with HIV (PLHIV) on ART, CD4+ T-cell counts fail to normalize despite ART and complete suppression of HIV viral load, resulting in severe immune dysfunction, which may represent an increased risk of clinical progression to AIDS and non-AIDS events as well as increased mortality. These patients are referred to as “immune inadequate responders”, “immunodiscordant responders” or “immune nonresponders (INR)”. The molecular mechanisms underlying poor CD4+ T-cell recovery are still unclear. In this sense, the use of omics sciences has shed light on possible factors involved in the activity and metabolic dysregulation of immune cells during the failure of CD4+ T-cell recovery in INR. Moreover, identification of key molecules by omics approaches allows for the proposal of potential biomarkers or therapeutic targets to improve CD4+ T-cell recovery and the quality of life of these patients. Hence, this review aimed to summarize the information obtained through different omics concerning the molecular factors and pathways associated with the INR phenotype to better understand the complexity of this immunological status in HIV infection.

Multi-omics in HIV: searching insights to understand immunological non-response in PLHIV

New insight into immune checkpoint inhibitors in the treatment of advanced renal cell carcinoma

Journal Article Accepted manuscript Current knowledge about long-term liver outcome among HBV/HIV coinfected patients Get access Cuiming Sun, Cuiming Sun The Second Department of Infectious Disease, The First Hospital of China Medical University, Shenyang, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Ziwei Yang, Ziwei Yang Department of Clinical Laboratory Medicine, The First Hospital of China Medical University, Shenyang, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Ying Wen Ying Wen The Second Department of Infectious Disease, The First Hospital of China Medical University, Shenyang, China Correspondence: Ying Wen, email: wenying666466@163.com Search for other works by this author on: Oxford Academic PubMed Google Scholar Clinical Infectious Diseases, ciae247, https://doi.org/10.1093/cid/ciae247 Published: 07 May 2024 Article history Received: 08 April 2024 Accepted: 02 May 2024 Published: 07 May 2024 

Current knowledge about long-term liver outcome among HBV/HIV coinfected patients.

T follicular helper (Tfh) cells and their interactions with B cells within the germinal center play extensive roles in human immunodeficiency virus (HIV) pathology. However, their association with immune reconstitution during antiretroviral therapy (ART) is still unclear. The aim of this study was to determine the impact of Tfh and memory B cell function on T helper cell recovery in patients with acute or chronic HIV infection. A total of 100 HIV‐infected individuals were enrolled in our study, classified into acute and chronic HIV infection groups (60 and 40, respectively), and subsequently classified into immunological responder (IR) and immunological nonresponder (INR) subgroups according to immune recovery outcomes after 96 weeks of ART. Liquid chromatography‐mass spectrometry was used to quantify the temporal regulation patterns of B and CD4+ T‐cell profiles among patients, and flow cytometry was used to investigate certain subsets of B and T cells. Here we showed that the prevalence of Tfh cells in the T helper cell population correlated negatively with CD4+ T‐cell recovery. The proportion of CXCR3− Tfh cells in patients with acute or chronic infection was associated with CD4+ T‐cell count recovery, and the proportion of CD21+ memory B cells at baseline was significantly higher in those with improved immune recovery outcomes. Universal proteomic dysregulation of B and CD4+ T cells at baseline was detected in patients with acute infected and poor CD4+ T‐cell recovery. Proteomics analysis revealed distinct temporal regulation profiles of both T helper cells and B cells between IRs and INRs among patients with acute infection. Our results suggest that the functions of memory B cells in INRs are dysregulated at the early stage of ART, possibly through disruption of Tfh cell function. The frequency and function of Tfh cells and their subsets are potential predictors of poor immune recovery.

Dysregulation of memory B cells and circulating T follicular helper cells is a predictor of poor immune recovery in HIV‐infected patients on antiretroviral therapy

Renal cell carcinoma (RCC), one of the most common genitourinary tumors, is induced by many factors, primarily smoking, obesity, and hypertension. As a non-acquired immunodeficiency syndrome (AIDS)-defining cancer, human immunodeficiency virus (HIV) may also play a critical role in the incidence and progression of RCC. It is evident that individuals who are infected with HIV are more likely than the general population to develop RCC. The age of RCC diagnosis among HIV-positive patients is younger than among HIV-negative individuals. However, many other characteristics remain unknown. With the increase in RCC incidence among HIV-infected patients, more research is being conducted to discover the relationship between RCC and HIV, especially with regard to HIV-induced immunodeficiency, diagnosis, and treatment. Unexpectedly, the majority of the literature suggests that there is no relationship between RCC and HIV-induced immunodeficiency. Nonetheless, differences in pathology, symptoms, or treatment in HIV-positive patients diagnosed with RCC are a focus. In this review, we summarize the association of RCC with HIV in terms of epidemiology, risk factors, diagnosis, and treatment.

Renal Cell Carcinoma Associated With HIV/AIDS: A Review of the Epidemiology, Risk Factors, Diagnosis, and Treatment

Background This study was the first to examine the association of baseline clinical factors with the rate of HBsAg clearance in a large retrospective cohort of Chinese patients with HIV/HBV coinfection treated with combination antiretroviral therapy (ART). Methods Our retrospective cohort included 431 patients with HIV/HBV coinfection treated with TDF-containing ART. The median follow-up was 6.26 years. Logistic regression was used to investigate the association of baseline variables with HBsAg clearance, and Cox regression was used to investigate the association of baseline variables with time to HBsAg clearance. Results The clearance rate of HBsAg in our study was 0.072 (95% CI 0.049~0.101). In the multivariate logistic regression, advanced age (OR=1.1, P=0.007), high CD4 cell count (OR=2.06, P=0.05), and HBeAg positivity (OR=8.00, P=0.009) were significantly associated with the rate of HBsAg clearance. The AUC of the model integrating the above three predictors was 0.811. Similar results were found in the multivariate Cox regression (HR = 1.09, P = 0.038 for age, HR = 1.05, P = 0.012 for CD4 count and HR = 7.00, P = 0.007 for HBeAg). Conclusions Long-term TDF-containing ART can lead to HBsAg clearance of 7.2% in Chinese patients with HIV/HBV coinfection. Advanced age, high CD4 cell count, and positive HBeAg at baseline could be regarded as potential predictors and biological markers for HBsAg clearance in patients with HIV/HBV coinfection.

/pdf/incidence-and-predictors-of-hbv-functional-cure-in-patients-ddxnl7j5.pdf

Incidence and predictors of HBV functional cure in patients with HIV/HBV coinfection: A retrospective cohort study

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Dysregulation of memory B cells and circulating T follicular helper cells is a predictor of poor immune recovery in HIV‐infected patients on antiretroviral therapy

Renal Cell Carcinoma Associated With HIV/AIDS: A Review of the Epidemiology, Risk Factors, Diagnosis, and Treatment

New insight into immune checkpoint inhibitors in the treatment of advanced renal cell carcinoma

Incidence and predictors of HBV functional cure in patients with HIV/HBV coinfection: A retrospective cohort study