Background: Defining the association of non-AIDS-defining events with inflammation and immune activation among human immunodeficiency virus (HIV)-infected persons with antiretroviral therapy (ART)-associated virological suppression is critical to identifying interventions to decrease the occurrence of these events.
Methods: We conducted a case-control study of HIV-infected subjects who had achieved virological suppression within 1 year after ART initiation. Cases were patients who experienced non-AIDS-defining events, defined as myocardial infarction, stroke, non-AIDS-defining cancer, non-AIDS-defining serious bacterial infection, or death. Controls were matched to cases on the basis of age, sex, pre-ART CD4(+) T-cell count, and ART regimen. Peripheral blood mononuclear cells and plasma specimens obtained at the visit before ART initiation (hereafter, baseline), the visit approximately 1 year after ART initiation (hereafter, year 1), and the visit immediately preceding the non-AIDS-defining event (hereafter, pre-event) were analyzed for activated CD4(+) and CD8(+) T cells, plasma interleukin 6 (IL-6) level, soluble tumor necrosis factor receptor I (sTNFR-I) level, sTNFR-II level, soluble CD14 level, kynurenine-to-tryptophan (KT) ratio, and D-dimer level. Conditional logistic regression analysis was used to study the association between biomarkers and outcomes, with adjustment for potential confounders.
Results: Higher IL-6 level, sTNFR-I level, sTNFR-II level, KT ratio, and D-dimer level at year 1 were associated with the occurrence of a non-AIDS-defining event. Significant associations were also seen between non-AIDS-defining events and values of these biomarkers in specimens obtained at baseline and the pre-event time points. Effects remained significant after control for confounders. T-cell activation was not significantly related to outcomes.
Conclusions: Interventional trials to decrease the incidence of non-AIDS-defining events among HIV-infected persons with virological suppression should consider targeting the pathways represented by these soluble markers. Clinical Trials Registration. NCT00001137.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192039 | PMC |
| http://dx.doi.org/10.1093/infdis/jiu254 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Plasma anti-CD4 IgG levels are associated with poor immune recovery in people with HIV initiating antiretroviral therapy.
AIDS
February 2025
Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY.
A segment of people with HIV on effective antiretroviral therapy (ART) continue to experience poor immune recovery, leaving them at heightened risk of non-AIDS-defining events (NAEs). The production of anti-CD4 IgG autoreactive antibodies is suggested as one contributing mechanism to these complications. Here, we found that plasma anti-CD4 levels do not discriminate immunological responders from nonresponders nor predict the occurrence of NAEs, suggesting it is unlikely a contributing immunopathological factor associated with these complications.
View Article and Find Full Text PDFThe risk of non-AIDS defining events is lower in ART-naive HIV controllers than in normal progressors on suppressive ART.
Clin Infect Dis
August 2024
Department of medical microbiology and infectious diseases, Erasmus MC, Rotterdam, the Netherlands.
Background: We aimed to compare the non-AIDS events (nADE) risk between normal progressors using ART (NP-ART) and people with HIV (PWH) that naturally control HIV infection (HIV controllers), as well as the outcomes after ART in HIV controllers on nADE.
Methods: The primary endpoint was major nADE defined as the composite of cardiovascular disease, non-AIDS malignancy or all-cause mortality, whichever came first..
Background: Non-AIDS defining malignancies present a growing challenge for persons with HIV (PWH), yet tailored interventions for timely cancer diagnosis are lacking. The Spanish IMPAC-Neo protocol was designed to compare two comprehensive cancer screening strategies integrated into routine HIV care. This study reports baseline data on the prevalence and types of precancerous lesions and early-stage cancer among participants at enrolment.
View Article and Find Full Text PDFTrends in Mortality in People With HIV From 1999 through 2020: A Multicohort Collaboration.
Clin Infect Dis
November 2024
Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Article Synopsis
- Mortality rates among people with HIV significantly dropped after the introduction of combination antiretroviral therapy, particularly between 1999 and 2009, but remained stable from 2010 to 2020.
- The study analyzed data from over 55,000 participants, revealing that AIDS-related deaths were most common in the earlier period, while deaths from non-AIDS-related malignancies increased in the later years.
- Despite the decline in overall mortality, the reduction was not entirely attributed to better immune function or the presence of other risk factors, suggesting other contributing elements may be at play.
Background: People living with HIV (PLWH) and receiving antiretroviral therapy (ART) have a goal of achieving and maintaining viral suppression; however, the existence of PLWH that show events of low-level viremia (LLV) between 50 and 1000 copies/mL and with different virological consequences have been observed. Moreover, some reports indicate that LLV status can lead to residual immune activation and inflammation, leading to a higher occurrence of non-AIDS-defining events (nADEs) and other adverse clinical outcomes. Until now, however, published data have shown controversial results that hinder understanding of this phenomenon's actual cause(s) and origin(s).
View Article and Find Full Text PDFWant 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!