AIDS research and human retroviruses最新文献

The epidemiology of human T-lymphotropic virus (HTLV) among sexual minority cisgender women (SMCW) remains poorly understood globally. We conducted a cross-sectional study of 251 SMCW in Belém, Brazilian Amazon, between March 2023 and April 2025. Participants underwent serological screening (ELISA) with molecular confirmation (qPCR). The prevalence of HTLV infection was 0.4% (1/251), with HTLV-2 identified in a 46-year-old asymptomatic bisexual woman with previous male partners and a current female partner. Serological testing showed strong ELISA reactivity (OD ratio 3.8), and qPCR confirmed HTLV-2 with a Ct value of 28.4 for the pol gene, while HTLV-1 remained negative. This represents the first documented HTLV-2 case in SMCW in the Amazon region, demonstrating viral circulation in an understudied population. Despite the low prevalence, comparable to the general population, these findings highlight the need for inclusive epidemiological surveillance and culturally sensitive prevention strategies for LGBTQIA+ communities in endemic regions.

Yunnan Province has historically been a major gateway for the introduction of HIV-1 into China. The border region with northern Myanmar has become a significant hotspot for HIV-1 recombination. This study identified and characterized a novel circulating recombinant form (CRF) of HIV-1 in the area, designating it as CRF181_BC. This viral strain was detected in three cases of heterosexual transmission in Baoshan City, Yunnan Province, China. Phylogenetic analysis of the near-full-length genome revealed that the three sequences formed a distinct branch, separate from all recognized subtypes and CRFs. The recombinant structure comprises 12 alternately distributed B and C subtype fragments, with subtype B accounting for 55.1% of the genome length. This contrasts with other known CRF_BC strains, which typically have a C-subtype backbone. Bayesian analysis revealed that this recombinant virus emerged between 2005 and 2006, coinciding with Yunnan Province's critical transition from HIV transmission dominated by injection drug use to HIV transmission predominantly occurring through sexual contact. The discovery of CRF181_BC underscores the intricate genetic diversity of HIV-1 and ongoing active recombination events along the China-Myanmar border. This poses new challenges for local viral diagnosis, treatment, and vaccine development.

The number and proportion of HIV/AIDS cases among older people in China have increased continuously and rapidly in recent years, with a more pronounced increase in males. In this study, we report a novel HIV-1 second-generation unique recombinant form isolated from a 79-year-old man in Hangzhou, for whom nonmarital commercial heterosexual contact as the potential transmission route. Phylogenetic analysis of the near full-length genome (NFLG) of strain 24HZ0410 reveals that a small genomic segment of CRF01_AE is inserted into the CRF07_BC backbone. Two recombinant breakpoints were observed in the tat and env gene regions, respectively. Our findings provide insight and a scientific basis in the genetic diversity in China. In addition, further molecular epidemiological surveillance of HIV-1 should be emphasized and strengthened among the elderly population in this region.

To explore the mechanism of action of San Ren Decoction (SRD) in people living with HIV (PLWH) treatment using network pharmacology, molecular docking technology, and cellular experiments. The active ingredients and potential targets of the Chinese traditional herb in SRD were determined from traditional Chinese Medicine Systems Pharmacology and Bioinformatics Analysis Tool for Molecular Mechanism of traditional Chinese medicine. The therapeutic targets of SRD in AIDS were identified using GeneCards, OMIM, DisGeNET, and DrugBank. The overlap between disease and component targets was determined to identify the potential targets of SRD in AIDS. The network of "Chinese herbs-active ingredients-targets" for SRD was accessed using Cytoscape. A protein-protein interaction network was prepared using STRING. The Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to perform enrichment analysis of signaling pathways. Molecular docking experiments and visualization of results were performed using Auto Dock Vina and PyMOL. Based on the results of network pharmacology, a drug-containing serum was prepared through cellular experiments. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples of PLWH and divided into three groups: the PLWH group, the PLWH + PI3K/Akt inhibitor group, and the PLWH + SRD drug-containing serum group (represented by PLWH, ZSTK474, and SRD, respectively). Healthy human PBMCs were used in the control group. After grouped culturing, quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were performed to detect and confirm gene and protein expression in each group. Quercetin, luteolin, myristic acid, honokiol, arachidonic acid, and other core components were the active ingredients in SRD. The core targets of SRD in AIDS included CAV1, SRC, HSP90AA1, AKT1, PI3K, STAT1, and RAF1. Gene ontology functional enrichment analysis revealed the positive regulation of gene expression, the response to foreign stimuli, and other observations. KEGG pathway enrichment analysis showed the involvement of the PI3K/Akt, TLR, and other pathways. Molecular docking results indicated that the primary active ingredients of SRD exhibited stable binding with the core proteins. In vitro and in vivo experiments showed that the mRNA and protein levels of AKT1, Caspase8, mTOR, PI3K, STAT1, and Bcl-2 were higher in PLWH. SRD may help regulate PLWH by inhibiting the PI3K/Akt signaling pathway. The results of this study indicated that SRD may play a role in PLWH treatment through multiple components and multiple targets to regulate the PI3K/Akt signaling pathway.

DNA methylation is a hallmark of aging; yet, our understanding of epigenetic age acceleration (EAA) in relationship to frailty in people with HIV (PWH) is poor. We conducted an observational study among PWH from the Veterans Aging Cohort Study (VACS) to test the hypothesis that EAA markers were associated with frailty. Epigenome-wide DNA methylation data from blood samples were used to derive EAA markers based on four established epigenetic clocks: Horvath, Hannum, PhenoAge, and GrimAge. Frailty was defined using a previously studied VACS frailty-related phenotype based on ≥1 survey item characterizing frailty factors: exhaustion, slowness, low physical activity, or weight loss. Logistic regression tested the association of participant characteristics and EAA markers with frailty. Adjusted models included each EAA marker as the independent variable, with significant participant characteristics as covariates. Among 1,076 PWH, frailty was evident in 397 (36.9%) individuals. The characteristics associated with frailty included chronological age, CD4⁺ T-cell count, HIV-1 RNA viral load, smoking, and age-related comorbid conditions. GrimAge acceleration (GrimAA), PhenoAge acceleration (PhenoAA), and HannumAge acceleration (HannumAA) were associated with frailty, but HorvathAge acceleration (HorvathAA) was not. The strength of the association was attenuated with adjustment for characteristics but remained significant for the three markers. Age acceleration based on GrimAA (values >0) was independently associated with a 45% increased odds of frailty (OR_adj: 1.45, 95% CI, 1.10, 1.93). In post hoc analyses, only GrimAA was associated with exercise frequency. In conclusion, select EAA markers were associated with frailty, independently of the traditional predictors of frailty. GrimAA, in particular, may be useful in future research to develop treatment strategies for frailty tailored to PWH.

In China, the HIV-1 epidemic is predominantly dominated by the recombinant strains CRF01_AE and CRF07_BC. The high replication rate, error-prone reverse transcriptase, and frequent recombination events of HIV-1 have facilitated the emergence of circulating recombinant forms (CRFs) between these major lineages. In this study, a novel HIV-1 second-generation circulating recombinant form (CRF193_0107), consisting of CRF01_AE and CRF07_BC, was identified during routine molecular surveillance in Hebei Province, China. We successfully obtained near-full-length genome (NFLG) sequences from three samples with no epidemiological link and performed phylogenetic, recombination, and temporal evolutionary analyses. Phylogenetic analysis revealed that these NFLG sequences formed a distinct monophyletic cluster with a high bootstrap value. Recombination analysis showed that all NFLGs shared the same unique mosaic recombination pattern between CRF01_AE and CRF07_BC clades, with one CRF07_BC fragment in the vif-vpr-tat region (HXB2 positions 5,550-5,965) inserted into a CRF01_AE backbone. Further subregion phylogenetic analysis confirmed that segment I+III of CRF193_0107 originated from men who have sex with men (MSM)-associated CRF01_AE cluster 4, and segment Ⅱ from MSM-associated CRF07_BC cluster N. The temporal evolution analysis indicated that CRF193_0107 originated in 2016. The emergence of CRF193_0107 underscores the importance of monitoring HIV-1 second-generation recombinant forms (CRFs_0107), particularly the transmission and evolution among men who have sex with men (MSM).

Human immunodeficiency virus type 1 (HIV-1) binds to CD4 receptors. Chemokine receptors such as C-C chemokine receptor type 5 (CCR5), C-C chemokine receptor type 2 (CCR2), and stromal-derived factor (SDF1) are involved in HIV cell entry, and mutations in the genes encoding these chemokine receptors and their ligands may play a role against HIV and acquired immunodeficiency syndrome (AIDS) progression. This study aims to investigate the frequency of the above polymorphisms within the Iranian population, evaluating their contribution to a protective genetic background against HIV acquisition and progression. Two hundred eighty-five healthy individuals and 100 people with HIV were selected. CCR5 genotyping was performed by polymerase chain reaction (PCR). CCR2 and SDF-1 polymorphism were analyzed by tetra-primer amplification refractory mutation system-polymerase chain (Tetra-ARMS-PCR). No CCR5-Δ32 mutants were found in either group. The screening for the CCR2 polymorphism yielded 44 (44%) and 127 (44.6%) heterozygous genotypes in the people with HIV and healthy individuals. Homozygous mutants were seen in 1 (1%) and 28 (9.8%) of the people living with HIV and healthy individuals, respectively, revealing a CCR2-64I allele frequency of 29.7%. CCR2-64I is associated with HIV resistance and reduced AIDS progression (p-value = .018). Among our 385 analyzed samples, 2 (2%) and 12 (4.2%) were found to be SDF1 heterozygous in persons with HIV and healthy individuals, respectively. Three (3%) of the people with HIV and 25 (8.8%) of the healthy individuals carried homozygous mutant variants. The allele frequency of the above polymorphism reached 9.1%, but no statistically significant association was observed, albeit it is borderline (p-value = .062). There are different distributions between people with HIV and healthy individuals, suggesting that CCR2-64I and SDF1-3'A may have a protective effect on HIV and that CCR2-64I (genotype I/I) has an effect on protecting against HIV and delaying progression from HIV status to AIDS. It could be used for prognostic genotyping in people with HIV.

Analytical treatment interruption (ATI) is a planned and monitored pause of ART used in HIV-related studies that enables measurement of viral rebound kinetics and immune responses, yet it may pose psychological risks to participants. Evidence has largely come from predominantly male cohorts in high-income settings; far less is known about how women living with HIV (WLHIV) in Southern Africa experience ATIs. We conducted a longitudinal sociobehavioral study nested within an ATI-inclusive Phase 2A clinical trial occurring in Durban, South Africa (NCT05281510). Twenty WLHIV who initiated ART during acute HIV and who were enrolled in an ATI clinical trial agreed to participate in this sociobehavioral research study. Participants completed validated psychological assessments at baseline (T1), pre-ATI (T2), post-ATI (T3), and end of clinical trial (T4). Outcomes included decisional certainty, self-esteem, resilience, anxiety, and depression; analyses were descriptive and stratified by time to ART restart: early restart (ER; <16 weeks, n = 6), delayed restart (DR; 16-44 weeks, n = 7), and long-term delayed restart (LTDR; >44 weeks, n = 6). Median decisional certainty increased from T1 4.70 (IQR 0.80) to T4 5.00 (0.00). Self-esteem remained high (T1 24.5; T4 26.0), with the largest gains in the DR group. Resilience was stable (median 4.75-4.50), rising modestly among participants in the LTDR group. Anxiety peaked pre-ATI (T2 33.3 [11.5]) then declined, except in the LTDR group, and anxiety and depression remained high (T4 anxiety 31.0; depression 8.0). ATI was well-tolerated across measures, anxiety spiked only pre-ATI and subsided, except in the LTDR group, where prolonged ATI kept both anxiety and depression elevated. These findings support the inclusion of South African WLHIV in ATI-inclusive clinical trials and highlight the need for psychosocial support for clinical trial participants.

The China-Myanmar border region is recognized as a hotspot for the emergence of HIV-1 recombinant forms. This study identified a novel HIV-1 circulating recombinant form (CRF) in this area, designated CRF184_BC. Near-full-length genome sequences were obtained from four individuals infected through heterosexual contact: one Chinese individual and three Burmese individuals. These sequences formed a distinct monophyletic clade with strong bootstrap support, separate from all known subtypes/CRFs. Recombination analysis revealed a conserved mosaic structure comprising four subtype C segments and three subtype B segments: I_C (790-2897), II_B (2898-3208), III_C (3209-5983), IV_B (5984-6435), V_C (6436-8821), VI_B (8822-8969), and VII_C (8970-9468). Bayesian Markov chain Monte Carlo analysis indicated that CRF184_BC emerged between the mid-2000s and the early 2010s. Identifying emerging CRFs highlights the ongoing dynamic evolution of HIV-1 in this region and emphasizes the need for enhanced molecular surveillance to inform effective public health strategies and vaccine development efforts.

The collection, storage, and transport of plasma, the ideal specimen for HIV-1 genotyping, is plagued by technical difficulties in resource-limited settings. We aimed to compare corresponding bio-samples for HIV-1 genotypic drug resistance testing. A total of 87 matched specimens of plasma, dried blood spots (DBS), and peripheral blood mononuclear cells (PBMCs) collected from 29 persons living with HIV (PLWH) in clinical, immunological, and/or virological failure were included. Drug resistance genotyping was done by nested PCR amplification and Sanger sequencing of the HIV-1 pol gene. The clinical reporting was based on the Stanford University HIV Drug Resistance Database. Amplification and genotyping success rates from the three sample types were compared. The level of agreement between the sample types was assessed using Cohen's kappa coefficient. In total, 89.7% (n = 26) of samples were amplified in plasma, 69% (n = 20) in DBS, and 100% (n = 29) in PBMC. In samples with plasma viral load >1,000 copies/mL, 96.2% were amplified in plasma, 73.1% in DBS, and 100% in PBMCs. The median number of mutations detected in plasma, DBS, and PBMCs was 6.5 (interquartile range [IQR]: 2-8.25), 5 (IQR: 0-6), and 5 (IQR: 2-7), respectively. The difference in the number of mutations across the three sample types was not statistically significant (p = 0.221). The agreement between the sample types was calculated based on susceptibility and resistance to different antivirals. The kappa values for nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors ranged from 0.70 to 0.88 and 0.75 to 0.87, respectively. Six samples showed discordance in HIV-1 drug resistance profiles when compared across the three compartments. DBS is a promising alternative to plasma for HIV-1 genotypic testing in resource-limited settings owing to the ease of sampling, storage, transportation, human resource efficiency, and cost-effectiveness. However, no single specimen type can satisfy all requirements and purposes. Selecting an appropriate specimen for a setting requires careful consideration of the practical constraints, logistical capacity, and application needs.