Assessing immune aging in HIV-infected patients.
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ABSTRACT:
SUBMITTER: Appay V
PROVIDER: S-EPMC5538339 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:ObjectiveSeveral pieces of evidence indicate that HIV-infected adults undergo premature aging. The effect of HIV and antiretroviral therapy (ART) exposure on the aging process of HIV-infected children may be more deleterious since their immune system coevolves from birth with HIV.DesignSeventy-one HIV-infected (HIV+), 65 HIV-exposed-uninfected (HEU), and 56 HIV-unexposed-uninfected (HUU) children, all aged 0-5 years, were studied for biological aging and immune senescence.MethodsTelomere length and T-cell receptor rearrangement excision circle levels were quantified in peripheral blood cells by real-time PCR. CD4 and CD8 cells were analysed for differentiation, senescence, and activation/exhaustion markers by flow cytometry.ResultsTelomere lengths were significantly shorter in HIV+ than in HEU and HUU children (overall, P < 0.001 adjusted for age); HIV+ ART-naive (42%) children had shorter telomere length compared with children on ART (P = 0.003 adjusted for age). T-cell receptor rearrangement excision circle levels and CD8 recent thymic emigrant cells (CD45RACD31) were significantly lower in the HIV+ than in control groups (overall, P = 0.025 and P = 0.005, respectively). Percentages of senescent (CD28CD57), activated (CD38HLA-DR), and exhausted (PD1) CD8 cells were significantly higher in HIV+ than in HEU and HUU children (P = 0.004, P < 0.001, and P < 0.001, respectively). Within the CD4 cell subset, the percentage of senescent cells did not differ between HIV+ and controls, but programmed cell death receptor-1 expression was upregulated in the former.ConclusionsHIV-infected children exhibit premature biological aging with accelerated immune senescence, which particularly affects the CD8 cell subset. HIV infection per se seems to influence the aging process, rather than exposure to ART for prophylaxis or treatment.
| S-EPMC4867984 | biostudies-literature
Project description:Access to antiretroviral therapy (ART) is improving worldwide. Immune reconstitution inflammatory syndrome (IRIS) is a common complication of ART initiation. In this review, we provide an overview of clinical and epidemiological features of HIV-associated IRIS, current understanding of pathophysiological mechanisms, available therapy, and preventive strategies. The spectrum of HIV-associated IRIS is described, with a particular focus on three important pathogen-associated forms: tuberculosis-associated IRIS, cryptococcal IRIS, and Kaposi's sarcoma IRIS. While the clinical features and epidemiology are well described, there are major gaps in our understanding of pathophysiology and as a result therapeutic and preventative strategies are suboptimal. Timing of ART initiation is critical to reduce IRIS-associated morbidity. Improved understanding of the pathophysiology of IRIS will hopefully enable improved diagnostic modalities and better targeted treatments to be developed.
| S-EPMC4334287 | biostudies-literature
Project description:ObjectiveThe purpose was to assess factors potentially affecting care pharmacists provide to HIV/AIDS patients including comfort level, confidence, education, experience, professional competence, continuity of care and patient-provider relationship between pharmacists and HIV-infected patients.MethodsA 24-item questionnaire assessed the constructs of this study. Surveys were distributed from October 2009 to April 2010 to pharmacists in Alabama with varying levels of experience treating HIV-infected patients. Chi-square tests determined whether relationships existed between responses, consisting of how often respondents reported treating HIV-infected patients, amount of HIV education respondents had, participants' confidence with HIV/AIDS knowledge and comfort level counseling HIV-infected patients about their medications.ResultsThirty-three percent of the pharmacists cared for HIV-infected patients on a monthly basis, yet 86% do not feel very confident with their HIV/AIDS knowledge. Forty-four percent were not comfortable counseling patients on antiretroviral medications, and 77% would feel more comfortable with more education. Significant, positive relationships were revealed concerning how often respondents treat HIV-infected patients and their comfort level counseling them (r=0.208, p<0.05). Similar relationships pertaining to the amount of education respondents had regarding HIV, how confident they are in their HIV/AIDS knowledge (r=0.205, p< 0.05), and their comfort level counseling HIV-infected patients on their medications (r=0.312, p<0.01) were found. The time spent treating HIV-infected patients and the education respondents had pertaining to HIV/AIDS related to increased comfort levels concerning counseling patients on their medications.ConclusionsThis research uncovered areas where pharmacists can improve care and treatment for HIV-infected patients. Increasing education on HIV/AIDS and treatment options may lead to increased comfort and confidence in therapeutic management. Through changes in pharmacists' perspectives and abilities to care for their patients, the patient-provider relationship could strengthen, potentially leading to improved medication compliance, enhanced overall health, and a better quality of life for HIV-infected patients.
| S-EPMC3780495 | biostudies-literature
Project description:Immune checkpoint molecules (ICMs) regulate T cell responses. In chronic viral infections and cancer, where antigens can persistently stimulate the immune system, ICMs can serve as a barrier to effective immune responses. The role of ICMs in the setting of systemic low-grade inflammation as in aging and antiretroviral therapy (ART)-suppressed HIV infection is not known. In this study, we made use of stored samples from the FLORAH cohort of HIV-infected ART-suppressed adults (age range 19-77 years.) and age-matched HIV-uninfected controls. We measured the expression levels of ICMs: PD-1, LAG-3, TIGIT, TIM-3, and 2B4 on resting CD4 and CD8 T cells and maturation subsets. To determine how expression of these molecules can affect T cell function, we stimulated peripheral blood mononuclear cell with HIV Gag or p09/H1N1 antigen and performed intracellular cytokine staining by multiparameter flow cytometry. ICMs were expressed at higher levels in CD8 compared with CD4. PD-1 was the only molecule that remained significantly higher in HIV-infected individuals compared with controls. LAG-3 expression increased with age in CD4 and CD8 T cells. 2B4 expression on CD8 T cells was negatively associated with IL-2 production but showed no effect on CD4 T cell function. TIM-3 expression was negatively associated with IL-21 production in CD4 and CD8 T cells and also negatively correlated with flu vaccine responses in HIV-negative individuals. Taken altogether, this study demonstrates the marked variation in ICM expression in T cells among adults and sheds light on the biology of these molecules and their effects on antigen-specific T cell functions. Overall, our results point to TIM-3 as a potential biomarker for immune function in HIV+ individuals on ART.
| S-EPMC6862963 | biostudies-literature
Project description:Escherichia coli strain:HIV infected patients | isolate:HIV infected patients Genome sequencing
| PRJNA756167 | ENA
Project description:Escherichia coli strain:HIV infected patients | isolate:HIV infected patients Genome sequencing
| PRJNA756169 | ENA
Project description:Biological aging is associated with immune activation (IA) and declining immunity due to systemic inflammation. It is widely accepted that HIV infection causes persistent IA and premature immune senescence despite effective antiretroviral therapy and virologic suppression; however, the effects of combined HIV infection and aging are not well defined. Here, we assessed the relationship between markers of IA and inflammation during biological aging in HIV-infected and -uninfected populations. Antibody response to seasonal influenza vaccination was implemented as a measure of immune competence and relationships between IA, inflammation, and antibody responses were explored using statistical modeling appropriate for integrating high-dimensional data sets. Our results show that markers of IA, such as coexpression of HLA antigen D related (HLA-DR) and CD38 on CD4+ T cells, exhibit strong associations with HIV infection but not with biological age. Certain variables that showed a strong relationship with aging, such as declining naive and CD38+ CD4 and CD8+ T cells, did so regardless of HIV infection. Interestingly, the variable of biological age was not identified in a predictive model as significantly impacting vaccine responses in either group, while distinct IA and inflammatory variables were closely associated with vaccine response in HIV-infected and -uninfected populations. These findings shed light on the most relevant and persistent immune defects during virological suppression with antiretroviral therapy.
| S-EPMC5846952 | biostudies-literature
Project description:As HIV-infected adults on successful antiretroviral therapy (ART) are expected to have close to normal lifespans, they will increasingly develop age-related comorbidities. The objective of this cross-sectional study was to compare in the French Dat'AIDS cohort, the HIV geriatric population, aged 75 years and over, to the elderly one, aged from 50 to 74 years. As of Dec 2015, 16,436 subjects (43.8% of the French Dat'AIDS cohort) were aged from 50 to 74 (elderly group) and 572 subjects (1.5%) were aged 75 and over (geriatric group). Durations of HIV infection and of ART were slightly but significantly different, median at 19 and 18 years, and 15 and 16 years in the elderly and geriatric group, respectively. The geriatric group was more frequently at CDC stage C and had a lower nadir CD4. This group had been more exposed to first generation protease inhibitors and thymidine analogues. Despite similar virologic suppression, type of ART at the last visit significantly differed between the 2 groups: triple ART in 74% versus 68.2%, ART ≥ 4 drugs in 4.7% versus 2.7%; dual therapy in 11.6% versus 16.4% in the elderly group and the geriatric group, respectively. In the geriatric group all co-morbidities were significantly more frequent, except dyslipidemia, 4.3% of the elderly group had ≥4 co-morbidities versus18.4% in the geriatric group. Despite more co-morbidities and more advanced HIV infection the geriatric population achieve similar high rate of virologic suppression than the elderly population. A multidisciplinary approach should be developed to face the incoming challenge of aging HIV population.
| S-EPMC6150468 | biostudies-literature
Project description:ABTRACT Many sources have highlighted the high incidence of premature cardiovascular events in HIV infected patients. This raises the suspicion of an accelerated aging of the vascular system in this disease characterized by chronic systemic subliminal inflammation and immune dysregulation. Unfortunately all currently available risk assessment algorithms based on traditional risk factors, and even those containing more HIV-specific factors, fail to accurately predict risk in a large proportion of patients. In the general population several models have implemented imaging data to refine risk assessment, and the concept of vascular aging has been of value in improving the performance of these algorithms. It is expected that HIV patients may benefit from a similar approach as it becomes clearer that vascular imaging provides valuable prognostic information in this patient category.
| S-EPMC5538336 | biostudies-other
Project description:We conducted a nested case-control study in a cohort of patients initiating antiretroviral therapy (ART) to identify risk factors and common manifestations of immune reconstitution inflammatory syndrome (IRIS) and to validate the Robertson criteria for IRIS prediction. HIV-infected patients at the Tuberculosis Research Centre clinics, Chennai and Madurai, India, initiating ART between July 2004 and June 2005 were prospectively studied. Of 97 patients (62% men, median age 32 years, median CD4 count 63 cells/μL) included, 34 developed IRIS. IRIS was more common in patients with a prior history of tuberculosis (74% versus 52%, P = 0.04), median time to development was 46 days and the sensitivity and specificity of the Robertson criteria to predict IRIS were 91% and 22%, respectively. In this population, IRIS was a common event, more so among patients with prior tuberculosis, and neither the rate of CD4 increase nor the Robertson criteria were useful in predicting its development.
| S-EPMC5592838 | biostudies-literature