AIDS research and human retroviruses最新文献

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.

Heterosexual transmission (HETE) represents the predominant method of transmission for the human immunodeficiency virus type 1 (HIV-1) in Shijiazhuang, Hebei Province, China. The number of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) continues to increase in this region. In the present study, two novel URFs (TFH010919 and TFH010944) were identified, both derived from HETEs in the Shijiazhuang area. The phylogenetic and recombination breakpoint analyses conducted on the near-full-length genomes of the two novel URFs revealed that the CRF01_AE strains serve as the predominant backbones for both TFH010919 and TFH010944. TFH010919 is a second-generation recombinant form composed of CRF01_AE and CRF07_BC, whereas TFH010944 is formed by the combination of CRF01_AE and CRF68_01B. This finding indicates that HIV-1 prevalence among HETEs remains a significant concern, driven by complex sexual networks that facilitate the spread of diverse recombinant strains, providing more opportunities for the recombination of viruses. The emergence of these new URFs revealed the ongoing evolution of HIV-1 and underscores the critical need for continuous monitoring of viral diversity in Hebei Province and surrounding regions to control HIV-1 transmission within the vulnerable population and beyond.

Despite increased HIV testing and access to treatment in Australia, presentations with advanced disease occur, placing a significant burden on the health system. We sought to describe costs associated with HIV care in the first year post diagnosis in a specialized, tertiary-level HIV service and identify factors predicting increased health care costs. People newly diagnosed with HIV from 2016 to 2020 were included in the study. Data were gathered regarding their demographics (age, gender, birthplace, and first language), HIV parameters (viral load [VL] and CD4 cell count), antiretroviral therapy start date, opportunistic illness history, and health care costs (inpatient, outpatient, and emergency) from 12 months of diagnosis. Multivariable modeling was used to identify factors associated with increased costs. We identified 147 people; median age 38 years, 90% male, median CD4 count at diagnosis 338 cells/µL with median initial cost of care AUD $22,929 (interquartile range $11,902-$39,175). Costs associated with advanced HIV diagnosis (CD4 < 200 cells/µL; n = 52) were more than double an early HIV diagnosis (CD4 ≧ 350 cells/µL; n = 69) (median $46,406 vs. $20,274; p < .001). In univariate analysis, older age, higher VL, low CD4 count, and VL >200 copies/mL after 6 months were associated with increased costs. In multivariate analysis, older age (p = .001) and CD4 count <200 cells/µL (p = .001) were the only factors predicting increased cost in the first year after HIV diagnosis. Prioritizing HIV testing strategies to allow earlier diagnosis of HIV would significantly reduce the financial burden of HIV care.

HTLV-1 is the etiologic agent of adult T-cell leukemia/lymphoma (ATL/ATLL) and is related to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The factors that influence the development of the disease remain unknown. The majority of patients with HTLV-1 infection remain asymptomatic throughout their lives, while 2.5%-5% developed ATLL and 0.3%-2% HAM/TSP. About 10 to 20 million people worldwide are infected with HTLV-1. In Argentina, HTLV-1 infection has been documented particularly in the northeast provinces neighboring Bolivia and Paraguay. This study aims to analyze the nine complete genomes of HTLV-1 from asymptomatic and symptomatic patients using next-generation sequencing. Mutation analysis and identification of viral integration sites were performed. Mutation analysis revealed distinct mutation patterns, identifying clusters associated with patients with HAM/TSP and lymphoma. Multiple integration sites across different chromosomes were found, suggesting random integration without specific hotspots. A defective provirus was identified in a patient with lymphoma, potentially impacting immune evasion and clonal expansion. Complete HTLV-1 genome sequences from circulating strains in Argentina were obtained for the first time. This contributes to the knowledge of the genetic variability of the virus and its integration sites in the human genome and reveals that the nature of the HTLV-1 provirus in natural infection is complex.

Previously, we reported a T69S insertion in the circulating recombinant form 06_cpx in a patient infected with HIV-1 during the perinatal period. Through this study, we found that the T69S insertion in our previous report was actually an S68S insertion. The patient was treated with zidovudine and didanosine, followed by combination antiretroviral therapy. The introduction of Korean Red Ginseng (KRG) completely suppressed plasma viral RNA to <20 copies/mL and reverted the S68S insertion to wild-type; there was no evidence of an S68S insertion for 3 years. Here, we report the impact of integrase strand transfer inhibitor (INSTI) treatment on drug resistance mutations (DRMs) over a further 10 years. The S68S insertion disappeared after 3 months of INSTI therapy, and the number of DRMs decreased. There were no major DRMs to INSTI in either the patient or her parents. These data highlight the utility of combination therapy with INSTI and KRG.

The global fight against human immunodeficiency virus (HIV) is complicated by its extensive genetic diversity, which arises from high mutation rates, rapid replication, and frequent recombination events. These factors lead to the emergence of numerous recombinant forms of HIV-1, contributing to the virus's adaptability and complicating prevention and treatment efforts. In this study, we identified two novel, unique recombinant forms (URFs) of HIV-1, CRF01_AE/CRF79_0107 and CRF01_AE/CRF07_BC, through near full-length genome sequence analysis. These URFs were detected in two individuals within the student men who have sex with men (MSM) population of Shijiazhuang, Hebei Province, China. Both utilized CRF01_AE as the underlying template, and PQ585802 represents a second-generation recombinant form comprising CRF01_AE and CRF79_0107. It is a novel recombinant form that was initially identified. PQ585803 represents a second-generation recombinant form, composed of CRF01_AE and CRF07_BC, and exhibits distinctive characteristics when compared to previously identified recombinant forms. This study underscores the urgent need for targeted public health measures focusing on high-risk populations, such as MSM and students, to curb the spread of HIV-1. Tailored education, enhanced access to prevention services, and strategies addressing risky behaviors are critical in reducing HIV-1 prevalence and mitigating the challenges posed by recombinant forms.

A workshop entitled Beyond 2010: Gaps, Challenges, and Priorities for the Future of Preclinical HIV Pre-Exposure Prophylaxis (PrEP) was sponsored by the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), on October 20-21, 2009, in Bethesda, Maryland. The objective of the workshop was to identify the main gaps in current knowledge, challenges, and priorities for the establishment of a PrEP preclinical pipeline and to also provide guidance for future directions of the field and DAIDS activities in this area. This 2-day workshop, through various presentations and breakout group discussions, specifically addressed four main topics that will be critical in identifying and advancing the next generation of PrEP candidates for clinical testing. The topics were (1) drug discovery, (2) pharmacokinetics (PK) and pharmacodynamics (PD), (3) animal models, and (4) delivery systems for prolonged activity. We report here a summary of the presentations and highlights of salient discussion topics from this workshop.