AI Article Synopsis
- The study focuses on understanding the immune dysregulation in people living with HIV who are on combination antiretroviral therapy, aiming to identify new biomarkers and drug targets through a comprehensive multi-omics approach.
- Researchers are analyzing a large cohort of PLHIV, including untreated spontaneous controllers, utilizing various methods such as genomics, proteomics, and clinical assessments over a two-year period.
- The study includes a diverse population with notable extreme phenotypes, allowing for a thorough examination of immune responses and potential therapeutic interventions in the context of HIV infection.
Article Abstract
Background: Even during long-term combination antiretroviral therapy (cART), people living with HIV (PLHIV) have a dysregulated immune system, characterized by persistent immune activation, accelerated immune ageing and increased risk of non-AIDS comorbidities. A multi-omics approach is applied to a large cohort of PLHIV to understand pathways underlying these dysregulations in order to identify new biomarkers and novel genetically validated therapeutic drugs targets.
Methods: The 2000HIV study is a prospective longitudinal cohort study of PLHIV on cART. In addition, untreated HIV spontaneous controllers were recruited. In-depth multi-omics characterization will be performed, including genomics, epigenomics, transcriptomics, proteomics, metabolomics and metagenomics, functional immunological assays and extensive immunophenotyping. Furthermore, the latent viral reservoir will be assessed through cell associated HIV-1 RNA and DNA, and full-length individual proviral sequencing on a subset. Clinical measurements include an ECG, carotid intima-media thickness and plaque measurement, hepatic steatosis and fibrosis measurement as well as psychological symptoms and recreational drug questionnaires. Additionally, considering the developing pandemic, COVID-19 history and vaccination was recorded. Participants return for a two-year follow-up visit. The 2000HIV study consists of a discovery and validation cohort collected at separate sites to immediately validate any finding in an independent cohort.
Results: Overall, 1895 PLHIV from four sites were included for analysis, 1559 in the discovery and 336 in the validation cohort. The study population was representative of a Western European HIV population, including 288 (15.2%) -women, 463 (24.4%) non-whites, and 1360 (71.8%) MSM (Men who have Sex with Men). Extreme phenotypes included 114 spontaneous controllers, 81 rapid progressors and 162 immunological non-responders. According to the Framingham score 321 (16.9%) had a cardiovascular risk of >20% in the next 10 years. COVID-19 infection was documented in 234 (12.3%) participants and 474 (25.0%) individuals had received a COVID-19 vaccine.
Conclusion: The 2000HIV study established a cohort of 1895 PLHIV that employs multi-omics to discover new biological pathways and biomarkers to unravel non-AIDS comorbidities, extreme phenotypes and the latent viral reservoir that impact the health of PLHIV. The ultimate goal is to contribute to a more personalized approach to the best standard of care and a potential cure for PLHIV.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9809279 | PMC |
| http://dx.doi.org/10.3389/fimmu.2022.982746 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Impact of COVID-19, lockdowns and vaccination on immune responses in a HIV cohort in the Netherlands.
Front Immunol
January 2025
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
Article Synopsis
- The COVID-19 pandemic influenced population-level immune responses through infections, lockdowns, and vaccination efforts, potentially impacting various immune-mediated diseases.
- In a study of 1,895 asymptomatic individuals living with HIV, researchers assessed how these factors modified inflammatory profiles and immune responses between October 2019 and October 2021.
- Results showed that while mild COVID-19 infections had minimal long-term immune effects, lockdowns significantly increased immune responsiveness, and vaccinations moderately reduced it, suggesting lockdowns may have unexpected immunological consequences that warrant further investigation.
Innate Immune Cell Functions Contribute to Spontaneous HIV Control.
Curr HIV/AIDS Rep
November 2024
Department of Internal Medicine and Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA, Nijmegen, The Netherlands.
Purpose Of Review: To review the role of innate immune cells in shaping the viral reservoir and maintenance of long-term viral control of spontaneous Elite and Viremic HIV controllers.
Recent Findings: HIV controllers exhibit a smaller and transcriptionally suppressed viral reservoir. Different studies report that early responses from innate cells play a pivotal role in this reservoir configuration.
Plasma proteomic signatures of liver steatosis and fibrosis in people living with HIV: a cross-sectional study.
EBioMedicine
November 2024
Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands; Department of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Background: Insights into the mechanisms driving metabolic dysfunction-associated steatotic liver disease (MASLD) in people living with HIV (PLHIV) remain limited. Plasma proteomics holds promise for biomarker discovery and the elucidation of biological mechanisms.
Methods: We performed cross-sectional analyses on data from 1036 virally suppressed PLHIV using antiretroviral treatment (ART) from the Dutch multi-centre 2000HIV cohort.
Liver Steatosis is Prevalent in Lean People With HIV and Associated With Exposure to Antiretroviral Treatment-A Cross-sectional Study.
Open Forum Infect Dis
June 2024
Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Background: Steatotic liver disease is suggested to have a higher prevalence and severity in people with HIV (PHIV), including in those with a normal body mass index (BMI). In this study, we used data from the 2000HIV cohort to (1) assess the prevalence of liver steatosis and fibrosis in lean versus overweight/obese PHIV and (2) assess associations in these subgroups between steatosis and fibrosis with traditional risk factors and HIV-specific characteristics.
Methods: The 2000HIV study cohort comprises 1895 virally suppressed PHIV that were included between 2019 and 2021 in 4 HIV treatment centers in the Netherlands.
HIV immunological non-responders are characterized by extensive immunosenescence and impaired lymphocyte cytokine production capacity.
Front Immunol
May 2024
Department of Internal Medicine and Infectious Diseases, OLVG, Amsterdam, Netherlands.
Article Synopsis
- Immunological non-responders (INR) are HIV patients with persistently low CD4+ T-cell counts despite effective antiretroviral therapy, putting them at higher risk for health issues.
- A study comparing INR to immunological responders (IR) found that INR had older age, more severe HIV prior to treatment, and lower CD4+ T-cell counts, with an increase in activated and exhausted CD4+ T-cells.
- The research highlighted that INR demonstrated impaired lymphocyte cytokine production, while innate immune responses remained similar, suggesting a potential benefit of anti-PD1 therapy for this group.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!