AIDS research and human retroviruses最新文献

As innate immune cells, granulocytic eosinophils form part of the first line of defense against pathogens. While recent studies indicate that granulocytes have additional functions including anti-inflammatory roles, tissue homeostasis maintenance, remodeling, and trained innate immune memory, they remain understudied in viral infections, specifically in human immunodeficiency virus (HIV) infection. Using a rhesus macaque model of simian-human immunodeficiency virus (SHIV) infection, we evaluated the functional responses of peripheral granulocytes using a newly developed whole blood intracellular cytokine staining assay. We observed elevated secretion of interleukin 8 and reduced secretion of tumor necrosis factor α in peripheral eosinophils from SHIV-infected animals stimulated with lipopolysaccharide compared to experimentally naive animals. Our data suggest potential functional skewing of peripheral eosinophils towards an enhanced effector response against secondary stimuli, warranting further investigation into the mechanistic understanding of granulocyte functions to inform developing HIV therapeutics.

It remains unclear whether the history of switching antiretroviral therapy (ART) regimens is a stand-alone risk factor for lipid deterioration in people living with HIV (PLWH). This study aims to explore the relationship between ART regimen switching history and lipid profiles in PLWH. This is a retrospective analysis of data from individuals with HIV infection aged 16-82, enrolled at Jinyintan Hospital in Wuhan, China, between January 2018 and June 2022. We investigated the potential link between their history of switching ART regimens and their lipid profiles. Locally weighted scatter plot smoother (LOESS) curves were used to depict the dynamic changes in lipid profiles over time. Linear mixed-effects models were employed to assess the differences in lipid levels between individuals with and without a history of ART switches. Out of 708 patients with HIV who began ART between January 2018 and June 2022, 207 (29%) switched regimens at least once, while 501 (71%) remained on their initial regimen throughout the study. Individuals with a history of switching ART exhibited less favorable lipid profiles as identified by LOESS analysis. Linear mixed-effects models indicate that participants who had not previously altered their ART regimens displayed notably lower levels of total cholesterol to high-density lipoprotein (HDL) ratio, total cholesterol, and triglycerides compared to those with a history of ART regimen changes (total cholesterol to HDL ratio, difference -0.19, 95% CI: -0.34 to -0.04; total cholesterol, difference -0.13, 95% CI: -0.25 to 0.00; triglycerides, difference -0.27, 95% CI: -0.43 to -0.11). In contrast, individuals with a history of ART regimen switching had noticeably lower HDL cholesterol (HDL-C) levels [difference: 0.04; 95% confidence intervals (CI) 0.00 to 0.07]. This means that the history of switching ART regimens may be associated with lipid deterioration in PLWH.

Although HIV-1 infection has now become a treatable chronic condition and not the deadly illness it once was, the costs of that treatment are substantial, and each infection prevented saves both financial and other costs. In China, the most predominant subtypes are CRF07_BC, CRF01_AE, and CRF55_01B, and the various second-generation recombinants are produced from the recombination between these subtypes. HIV full-length genome sequences can provide important information on their epidemiology. In this study, we identified two unique recombinant forms (URFs) designated as JLCC230106 and XJWQ230011, which are composed of CRF01_AE/CRF07_BC and CRF07_BC/CRF55_01B, respectively. Phylogenetic and recombinant analyses utilizing near-full-length genome (NFLG) confirmed that these URFs originated from CRF01_AE/CRF07_BC and CRF07_BC/CRF55_01B strains. The emergence of novel recombinants is increasing the genetic diversity of HIV in China. This information can be shared with clinicians, human behavior specialists, or public health policymakers and used as an aid in discovering which methods are best or most cost-effective in combating the spread of HIV.

Kaposi sarcoma (KS) is a common malignancy for people living with HIV (PLWH), despite antiretroviral therapy (ART). Curiously, even with improved CD4⁺ T-cell counts and low viral loads following ART, some PLWH with KS may still experience KS progression or even death and require adjuvant chemotherapy to manage their KS. The factors associated with persistent or unresponsive KS after ART initiation remain poorly characterized, and biomarkers to identify patients at risk of KS progression are needed, particularly in resource-limited areas where access to chemotherapy is limited. Here we analyzed baseline KS tumor biopsies from PLWH with KS who required chemotherapy due to unresolved KS after ART initiation and those who did not require chemotherapy after ART initiation. By examining participant metadata and viral copy number for Kaposi sarcoma-associated herpesvirus (KSHV), HIV, cytomegalovirus, and Epstein-Barr virus and KSHV gene expression in the tumor biopsies prior to ART initiation, we identified a model of factors associated with KS progression after ART initiation, including biological sex, age, and the log ratio of KSHV/HIV copy number in the tumor. We believe that the ratio of KSHV/HIV may be linked to the cell types that each virus infects, and future work exploring the relationship between tumor and immune cells in the baseline tumors is planned. Innovation would be necessary to reduce costs and simplify the viral quantification assays, enabling the translation of these findings into routine clinical care, particularly in resource-limited settings.

Since combined antiretroviral therapy for human immunodeficiency virus-associated neurocognitive dysfunction (HAND) only slows the disease's progression, early identification and timely intervention are crucial for effective therapy. In this article, we review the latest evidence in body fluid biomarkers of HAND, providing an overview of research conducted on cerebrospinal fluid and blood samples to draw conclusions on promising biomarkers. Although the significance of biomarkers such as amyloid metabolites, tau proteins, neurofilament light chain, myelin oligodendrocyte glycoprotein, and brain-derived neurotrophic factor in the early detection of HAND may not be immediately clear, they could potentially play a crucial role in evaluating prognosis and tracking the effectiveness of treatment.

To assess the impact of anemia severity during antiretroviral therapy (ART) on in-hospital mortality among persons living with HIV. We conducted a retrospective cohort study of hospitalized persons living with HIV at the Fourth People's Hospital of Nanning, Guangxi, China, from 2018 to 2020. Kaplan-Meier analysis was used to calculate cumulative mortality rates. The Cox proportional hazards model, 1:1:1 propensity score matching (PSM), and three-group inverse probability of treatment weighting (IPTW) were used to assess the impact of anemia severity on mortality in hospitalized persons living with HIV. A total of 2,217 hospitalized persons living with HIV were included, among whom 409 (18.4%) had anemia: 50 (2.3%) with mild anemia, 174 (7.8%) with moderate anemia, and 185 (8.3%) with severe anemia. Among all AIDS-related complications, patients with severe anemia had a higher mortality rate [20.34/100 person-months, 95% confidence interval (CI): 13.29-27.39], significantly higher than that of persons living with HIV without anemia (7.74/100 person-months, 95% CI: 6.02-9.45); the adjusted hazard ratio (AHR) was 2.422, with a 95% CI of (1.500, 3.913). After PSM and IPTW analyses, results were similar, with PSM (AHR: 4.745, 95% CI: 2.231-10.091) and IPTW (AHR: 1.920, 95% CI: 1.146-3.216). Patients with CD4⁺ T cell counts below 350 per μL and severe anemia had an increased mortality risk. Severe anemia is an independent risk factor for in-hospital death in persons living with HIV in southern China. The importance of timely identification and assessment of anemia severity during ART and prompt treatment to correct anemia, which is crucial for improving anemia burden and prognosis for persons living with HIV.

Extraordinary HIV-1 recombination is occurring in China. Here, a novel second-generation circulating recombinant form (CRF174_0708) was found in Yunnan Province, China. First, Bootscanning revealed a mosaic structure with three subtype B segments inserted into a subtype C backbone. However, phylogenetic analysis showed that subregions 2B (2978-3267) and 4B (6023-6196) were related to CRF07_BC, whereas subregion 6B (8846-8997) was related to CRF08_BC, suggesting that the sequences could be recombined from CRF07_BC and CRF08_BC. Furthermore, Bootscanning-guided partitioning with subregion-specific phylogenetic analysis confirmed that subregions I (790-1902), III (2636-3746), V (4327-5825), VII (6023-6196) and IX (6379-6782) from CRF07_BC, and subregions II (1903-2635), IV (3747-4326), VI (5826-6022), VIII (6197-6378) and XI (7463-9512) from CRF08_BC. Bayesian dating traced the emergence to 2005-2007, consistent with the expansion of the parental strains. This discovery advanced our understanding of HIV-1 evolution.

Since HIV-1 is a retrovirus with a high mutation rate and recombination rate, the virus contains a variety of genotypes and recombinants. The men who have sex with men (MSM) population in Beijing has become the main group of HIV transmission, and the co-transmission of multiple HIV-1 subtypes in the same high-risk group has led to the continuous generation of recombinants between various subtypes. In this study, two unique recombinant forms were identified in the samples from Beijing, and the full-length sequences were amplified and sequenced for analysis. Through the construction of phylogenetic trees and recombination breakpoint analysis, the two recombinants were identified as second-generation recombinants composed of CRF01_AE and CRF07_BC. The emergence of more complex recombinant strains poses new challenges to HIV prevention, and it is necessary to focus on monitoring the epidemic in the MSM population.