AIDS research and human retroviruses最新文献

Yunnan Province is one of the provinces in China severely affected by HIV-1. To track the evolution and epidemiological characteristics of HIV-1 genetics in Yunnan Province, this study conducted a retrospective molecular epidemiological study of HIV-1 in new infections in Yunnan Province. From the newly reported HIV-infected individuals throughout Yunnan Province from January to March 2018, cases with CD4⁺ T lymphocytes less than 200 cells/µL were excluded for BED capture enzyme immunoassay (BED-CEIA). Samples identified as recent infections by BED-CEIA were subjected to viral gene amplification to analyze the distribution characteristics of HIV-1 genotypes and the prevalence of pretreatment resistance. Of the 1,740 samples tested by BED-CEIA, 448 were identified as newly infected, and 323 were successfully genotyped; 14 HIV-1 genotypes were identified, including 2 subtypes, 11 circulating recombinant forms (CRFs), and several unique recombinant forms (URFs), of which CRF08_BC (37. 5%, 121/323), CRF07_BC (22.6%, 73/323), URFs (18.3%, 59/323), and CRF01_AE (14.9%, 48/323) were the predominant genotypes. CRF08_BC had higher proportions in the northeastern, southeastern, central, and southwestern regions of Yunnan Province than in the northwestern region and was more common in the 40-49-year age group, married, and heterosexual contacts. CRF01_AE had significantly higher proportions in the southeastern and northwestern regions and among those with homosexual contact, whereas no significant correlations were found for CRF07_BC and URFs. The overall prevalence of pretreatment resistance was 8.5% [95% confidence interval (CI): 5.5%-12.4%], with the highest proportion of resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs; 6.0%, 95% CI: 3.5%-9.4%). This study demonstrated the genetic diversity and regional and subpopulation distribution characteristics of the recently infected HIV-1 population in Yunnan Province, and that pretreatment resistance was at a moderate level, but resistance to NNRTIs needs attention. This study provided the baseline data for a systematic study of the evolution of HIV-1 genetics in a typical endemic area.

The advances in antiretroviral therapy (ART) bring forth an ever-growing percentage of aging people living with HIV (PLHIV) with successful immune restoration (SIR) but increased comorbidities and reduced quality of life. The current criteria for SIR, CD4 absolute count (AC) >500 cells/µL, are proving not to be sufficiently informative enough for preventing or monitoring these unwelcome changes. Messenger RNA (mRNA) of genes, such as CXCL8, IL-6, and CSF-2, that have shown relations with HIV/HIV-associated comorbidities could represent early indicators of increase in viral load and/or pathological changes leading development of comorbidities. Our results display an underexpression of CXCL8 and IL-6 in ART+ PLHIV with CD4 AC >1,000, but not with CD4 AC <1,000, compared to ART-PLHIV and lower levels of CSF-2 mRNA in ART+ CD4 AC >1,000 compared to ART+ CD4 AC <1,000. Taken together, these findings indicate the need to stratify and expand HIV monitoring beyond CD4 AC >500.

HIV cure research has advanced, utilizing analytical treatment interruption (ATI) as a research tool alongside therapeutic strategies such as latency-reversing agents, block and lock strategies, immune-based therapies, cell and gene therapies, and combination approaches to overcome viral persistence. While promising, participation in cure trials remains limited, particularly for long-term survivors (LTS) who have lived with HIV for decades. Many LTS are willing to participate but face barriers such as age-based exclusions, comorbidities, and trial design constraints. With over half of the people with HIV in the United States aged 50 or older, addressing these barriers is crucial to designing inclusive, equitable, and representative cure trials. We conducted 32 semi-structured interviews with LTS of HIV, aged 60 years and older, recruited through community-based organizations and research networks across the United States. Participants were diverse in age, sex, gender, race, and ethnicity. We transcribed, anonymized, and analyzed interviews thematically. Most participants expressed a willingness to participate in HIV cure research, driven by a sense of responsibility and hope for future generations. However, concerns were raised about age-based exclusions from HIV cure trials, which many participants viewed as unjust given their long-term experience with HIV and commitment to finding a cure that could potentially benefit people of their age. Additional concerns included the risks of ATIs, such as viral rebound and the development of viral resistance, along with logistical challenges, including transportation and invasiveness of certain procedures. Despite these barriers, most LTS indicated they would participate in HIV cure trials if researchers addressed their concerns about safety, accessibility, and inclusion. LTS emphasized the need for transparent communication, clear informed consent, and flexible trial designs that accommodate their needs. By addressing these concerns, researchers can engage LTS more meaningfully in HIV cure research, enriching the field and promoting more inclusive and ethical study designs.

Persons with HIV (PWH) have disproportionate hepatitis C virus (HCV) infection prevalence and liver-related morbidity and mortality. These sequelae may be alleviated by curative direct-acting antiviral (DAA) treatment; however, longitudinal effects of DAAs on clinical biomarkers are not well-characterized. We included PWH enrolled in the HIV Outpatient Study (HOPS) who were prescribed DAAs and DAA-naïve PWH of comparable age, sex, race/ethnicity, and fibrosis-4 (FIB-4) profiles. We contrasted the DAA effect on longitudinal trajectories of immunological and hepatic markers using generalized linear mixed models (GLMM) from 2010 to 2020. Of 347 PWH/HCV coinfection, median age was 53.8 years, 30.5% were women, 67.1% were publicly insured, 44.4% were non-Hispanic Black, and 153 (44.1%) were prescribed DAAs (median follow-up = 3.55 years). In multivariable GLMM analysis, DAA treatment was associated with [mean (95% confidence interval)] faster decline in alanine aminotransferase of -7.86 mu/µL/year (-15.39, -0.33) and faster increase in platelets of 6.99 mu/µL/year (2.89, 11.09). Changes in aspartate aminotransferase were comparable between groups. FIB-4 decreased in the DAA-treated but not the DAA-naïve group: -0.26 (-0.41, -0.11) versus 0.02 (-0.16, 0.20)/year, respectively. There was a faster increase in cluster of differentiation (CD)4 count of 0.05 (0.03-0.08) and CD8 count of 0.04 (0.02-0.07) log cells/mL/year in the DAA-treated compared with the DAA-naïve group (p < .001), but not in the CD4/CD8 ratio (p = .36). Among U.S. PWH/HCV coinfection treated with DAAs, we found modest changes in immunological markers and substantial improvements in hepatic markers modeled over 4 years of DAA treatment. Curative DAA treatment is critical to mitigate advanced liver fibrosis.

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.