Current methods for detecting and assessing HIV-1 antibody resistance

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 6, 2025

Antiretroviral therapy is the standard treatment for HIV, but it requires daily use and can cause side effects. Despite being available decades, there are still 1.5 million new infections 700,000 deaths each year, highlighting need better therapies. Broadly neutralizing antibodies (bNAbs), which highly active against HIV-1, represent a promising approach clinical trials have demonstrated potential of bNAbs in prevention HIV-1 infection. However, antibody resistance (HIVAR) due to variants envelope glycoproteins (HIV-1 Env) not well understood yet poses critical problem treatment. HIVAR also plays an important role future development vaccine, will require elicitation circulating strains sensitive. In recent years, variety methods been developed detect, characterize predict HIVAR. Structural analysis antibody-HIV-1 Env complexes has provided insight into viral residues neutralization, while testing viruses susceptibility verified impact some these residues. addition, vitro neutralization adaption assays shaped our understanding bNAb based on sequence. Furthermore, vivo studies animal models revealed rapid emergence escape mono- or combined treatments. Finally, similar were found first HIV-1-infected patients. These structural, vitro, led identification validation almost all bNAbs. defined detection patients lacking novel, potent broad-spectrum bNAbs, clearly defined. Here, we review currently approaches detection, characterization prediction

Language: Английский

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Urgent Focus on the Surgical Risks of People Living With HIV: A Systematic Review and Meta‐Analysis

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(2)

Published: Feb. 1, 2025

ABSTRACT With the widespread promotion and application of antiretroviral therapy in clinical practice, people living with HIV (PLWH) have potential to live as long non‐HIV probability surgery for PLWH has been increasing dramatically. However, overall postoperative outcome risk are still unclear. We performed comprehensive methodical searches PubMed, Embase, Web Science without date language restrictions. Study outcomes included: (1) cure rate, (2) mortality, (3) reoperation (4) incidence any complications, (5) length stay, (6) operation duration. NOS scores were employed evaluate bias risk, while publication was assessed using funnel plots Egger tests. Review Manager version 5.4.1, R 4.4.1, Stata 14.0 determine quantitative analysis, considering a significance level p < 0.05. A total 50 studies included, involving 54 565 undergoing surgical treatment. Synthesis analysis showed that mortality (OR = 1.70, 95% CI: 1.58−1.83, 0.00001), rate 1.78, 1.36−2.34, complication 1.56, 1.26−1.95, LOS 1.63, 1.28−1.99, time 7.37, 1.14−13.59, 0.02) increased PLWH. there no significant difference compared control group 1.27, 0.90−1.79, 0.18). Subgroup rates again orthopedic 1.65, 1.34−2.05, 0.00001) general 1.72, 1.08−2.74, 0.02). type procedure, quality, study type, patient origin not sources heterogeneity. Meta‐regression CD4 count had effect on but anti‐retroviral 34.89% explanatory power. There is an death, reoperation, prolonged hospital stay duration conducting extensive prospective across multiple centers crucial validate these findings.

Language: Английский

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Yoda1, a Piezo1 agonist, induced latent HIV reactivation associated with upregulation of CD3/TCR complex and HLA genes

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

There is currently no cure for HIV because of the presence latent viral reservoirs in people with (PWH) on antiretroviral therapy (ART). Latency-reversing agents (LRAs) that can effectively reactivate and destroy are being developed as a possible HIV. Here, we identify Yoda1, Piezo1 agonist, novel LRA. Yoda1 reactivated vitro ACH2 cells ex vivo PBMCs from an patient ART. induced infectious virus production gene expression via activation calcium signaling. Transcriptomic proteomic analyses revealed unique reactivation pathway involving T cell activation, upregulation TCR/CD3 HLA genes, well modulation host transcription translation favors expression. These findings suggest further testing development effective LRA to

Language: Английский

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Assessing HIV-1 subtype C infection dynamics, therapeutic responses and reservoir distribution using a humanized mouse model

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 16, 2025

While HIV-1 subtype C (HIV-1C) is the most prevalent and widely distributed in HIV pandemic, nearly all current prevention therapeutic strategies are based on work with B (HIV-1B). HIV-1C displays distinct genetic pathogenic features from that of HIV-1B. Thus, treatment approaches developed for HIV-1B need to be suitably optimized HIV-1C. A suitable animal model will help delineate comparative aspects infections. Here, we used a humanized mouse evaluate infection, disease progression, response anti-retroviral therapy (ART) viral rebound following interruption. limited study prototypical virus was also performed. Viral immune cell dynamics, acquisition resistance anatomical reservoir distribution extended interrupted were compared. In comparison, lower early plasma viremia observed HIV-1C, but similar rate CD4+ T depletion as suppression by ART delayed infected group evidence, one case, acquired class wide integrase inhibitors, critical component global regimens. Also, animals displayed faster interruption (ATI). Disparate patterns tissue proviral DNA ATI suggestive sources rebound. this preliminary study, discernible differences noted between implications prevention, therapeutics curative strategies. Results here highlight utility hu-HSC future expanded studies context.

Language: Английский

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Therapeutic efficacy of albuvirtide-based antiretroviral therapy in people living with HIV who have low-level viremia and non-AIDS-defining malignancies: two case reports

Retrovirology, Journal Year: 2025, Volume and Issue: 22(1)

Published: April 18, 2025

Abstract Background People living with HIV (PLWH) who experience low-level viremia (LLV) face unique challenges in disease management, particularly when diagnosed concurrent malignancies. Albuvirtide (ABT), a long-acting fusion inhibitor approved China, has shown promise clinical trials for treatment-experienced individuals. However, its efficacy managing LLV the context of malignancies remains under-explored. Case presentation We report two cases PLWH developed non-AIDS-defining cancers(NADCs). The first individual lung squamous cell carcinoma, and second was breast cancer. Both patients received ABT as part their optimized antiretroviral therapy (ART) regimen during cancer treatment course. After optimization, both achieved viral suppression (HIV-1 RNA < 50 copies/mL) improvements CD4 + T counts. appropriate treatments according to practice guidelines. patient required an adjustment his PD-1 monotherapy due intolerance chemotherapy, whereas successfully completed her planned multimodal regimen. Conclusions These suggest potential benefits ABT-containing ART regimens have NADCs. While cannot establish definitive conclusions, they highlight need larger studies investigating role this complex scenario.

Language: Английский

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Detection of HIV-1 DNA/RNA in Peripheral Blood, Bone Marrow and Femoral Head of Patients with Osteonecrosis of the Femoral Head

Infection and Drug Resistance, Journal Year: 2024, Volume and Issue: Volume 17, P. 551 - 559

Published: Feb. 1, 2024

Background: With the increasing life expectancy of people living with HIV (PLWH) following antiretroviral therapy (ART), there is a growing prevalence chronic diseases such as osteonecrosis femoral head (ONFH). Compared more accessible blood, viral infection profile in bone marrow and necrotic heads PLWH remains inadequately characterized. Methods: Femoral were collected from 15 undergoing total hip arthroplasty. For each head, samples obtained subchondral, necrotic, sclerotic, normal areas. DNA RNA assays employed to evaluate disparities load reservoir between well quantify distinct regions head. Results: Blood dropped below detectable levels 8 patients (below 20 copies/mL). The median was 255.89 copies/mL. blood 296.35 454.31 copies/10 6 cells. area about half that sclerotic area, twice difference statistically significant. Conclusion: Despite using ART, still substantial active potential marrow. Viral transcription most which may indicate itself directly involved ONFH. Keywords: HIV, AIDS, marrow,

Language: Английский

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New Therapies and Strategies to Curb HIV Infections with a Focus on Macrophages and Reservoirs

Viruses, Journal Year: 2024, Volume and Issue: 16(9), P. 1484 - 1484

Published: Sept. 18, 2024

More than 80 million people worldwide have been infected with the human immunodeficiency virus (HIV). There are now approximately 39 individuals living HIV/acquired syndrome (AIDS). Although treatments against HIV infection available, AIDS remains a serious disease. Combination antiretroviral therapy (cART), also known as highly active (HAART), consists of treatment combination several drugs that block multiple stages in replication cycle. However, increasing usage cART is inevitably associated emergence drug resistance. In addition, development persistent cellular reservoirs latent critical obstacle to viral eradication since rebound takes place once anti-retroviral (ART) interrupted. Thus, efforts being applied new generations drugs, vaccines and types cART. this review, we summarize antiviral therapies used for HIV/AIDS, both individual agents therapies, highlight role macrophages most recent clinical studies related

Language: Английский

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Eliminating the HIV tissue reservoir: current strategies and challenges

Infectious Diseases, Journal Year: 2023, Volume and Issue: 56(3), P. 165 - 182

Published: Dec. 27, 2023

Background Acquired immunodeficiency syndrome (AIDS) is still one of the most widespread and harmful infectious diseases in world. The presence reservoirs housing human virus (HIV) represents a significant impediment to development clinically applicable treatments on large scale. viral load blood can be effectively reduced undetectable levels through antiretroviral therapy (ART), higher concentration HIV sequestered various tissues throughout body, forming tissue reservoir - source viremia after interruption treatment.

Language: Английский

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Characterization of the intestinal microbiota in MSM with HIV infection

BMC Microbiology, Journal Year: 2024, Volume and Issue: 24(1)

Published: June 3, 2024

Abstract Background HIV-infected persons demonstrate notable disturbances in their intestinal microbiota; however, the impact of microbiota on HIV susceptibility men who have sex with (MSM), as well effects and antiretroviral therapy (ART) gut microbiota, remains under active study. Thus, our research focuses clarifying distinctions composition among uninfected MSM non-MSM healthy controls, investigating alterations early-stage microbial communities following infection, assessing how ART affects microbiota. Methods This study enrolled four participant groups: MSM, Recent HIV-1 infection (RHI) ART, 30 individuals each group. We utilized 16S ribosomal DNA (16S rDNA) amplicon sequencing to analyze fecal employed Luminex multiplex assays measure plasma markers for translocation (LBP, sCD14) inflammatory marker CRP. Findings Comparing no substantial variances were observed α β diversity. Uninfected had higher average relative abundances Bacteroidetes, Prevotella , Alloprevotella while Bacteroides Firmicutes, Faecalibacterium lower abundances. diversity than RHI MSM. In Megasphaera Fusobacterium increased, Roseburia decreased at genus level. Additionally, treatment a non-nucleoside reverse transcriptase inhibitor (NNRTI) led significant compared The random forest model showed that biomarkers effectively distinguished between newly diagnosed HIV-negative an ROC AUC 76.24% ( 95% CI : 61.17-91.31%). Conclusions early imbalances after new infection. experienced worsened dysbiosis, indicating combined effect ART. NNRTI-based notably changed suggesting potential direct NNRTI drugs

Language: Английский

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HIV-Infected Hepatic Stellate Cells or HCV-Infected Hepatocytes Are Unable to Promote Latency Reversal among HIV-Infected Mononuclear Cells

Pathogens, Journal Year: 2024, Volume and Issue: 13(2), P. 134 - 134

Published: Feb. 1, 2024

Due to a common mode of transmission through infected human blood, hepatitis C virus (HCV) and immunodeficiency (HIV) co-infection is relatively prevalent. In alignment with this, HCV associated an increased size the HIV reservoir in highly active antiretroviral therapy (HAART)-treated individuals. Hence, it crucial comprehend physiological mechanisms governing latency reactivation reservoirs. Consequently, our study delves into interplay between HCV/HIV liver cells its impact on modulation latency. We utilized latently monocytic cell line (U1) T-cell (J-Lat) found that mediators produced by infection hepatic stellate hepatocytes HCV, respectively, were incapable inducing reversal under studied conditions. This may favor maintenance among mononuclear liver. Further investigations are essential elucidate role interaction regulating and/or reactivation, providing physiologically relevant model for comprehending microenvironments vivo.

Language: Английский

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