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Cardiac and inflammatory biomarkers in perinatally HIV-infected and HIV-exposed uninfected children.

ABSTRACT: OBJECTIVES:To compare distributions of serum cardiac and inflammatory biomarkers between perinatally HIV-infected (PHIV) and perinatally HIV-exposed uninfected (PHEU) children, to evaluate their associations with echocardiographic measures, and among PHIV youth, with antiretroviral therapy (ART) and HIV disease severity measures. DESIGN:Cross-sectional analysis of temporally paired serum samples for biomarkers and echocardiograms in a prospective multicenter cohort study of PHIV and PHEU youth. METHODS:Serum samples were analyzed among 402 youth in the PHACS Adolescent Master Protocol (AMP) for high-sensitivity cardiac troponin-T (hs-cTnT, a cardiomyocyte injury marker), N-terminal-pro-brain natriuretic peptide (NT-proBNP, a myocardial stress marker), and inflammatory markers [high-sensitivity C-reactive protein, interleukin (IL)-1, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-? (TNF-?), and soluble TNF receptor II (sTNF-RII)]. Echocardiograms were centrally measured and parameters converted to z cores to account for differences in age and body size. RESULTS:Compared with PHEU (N?=?156), PHIV youth (N?=?246) more often had detectable hs-cTnT and higher levels of sTNF-RII and IL-18. Higher inflammatory biomarkers were generally associated with higher left ventricular (LV) wall stress and lower LV function and LV mass in the two groups. Among PHIV youth, the biomarkers were more strongly associated with current rather than historical immunologic and virologic status. CONCLUSION:PHEU and PHIV have modest, significant differences in serum levels of specific inflammatory and active myocardial injury biomarkers. Higher biomarker levels were associated with lower LV mass and shifts in LV structure. Further study is warranted on the longitudinal role of cardiac and inflammatory biomarkers for targeting interventions among PHIV and PHEU youth.

SUBMITTER: Wilkinson JD

PROVIDER: S-EPMC6387791 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Cardiac and inflammatory biomarkers in perinatally HIV-infected and HIV-exposed uninfected children.

Wilkinson James D JD Williams Paige L PL Yu Wendy W Colan Steven D SD Mendez Armando A Zachariah Justin P V JPV Van Dyke Russell B RB Shearer William T WT Margossian Renee E RE Lipshultz Steven E SE

AIDS (London, England) 20180601 10

<h4>Objectives</h4>To compare distributions of serum cardiac and inflammatory biomarkers between perinatally HIV-infected (PHIV) and perinatally HIV-exposed uninfected (PHEU) children, to evaluate their associations with echocardiographic measures, and among PHIV youth, with antiretroviral therapy (ART) and HIV disease severity measures.<h4>Design</h4>Cross-sectional analysis of temporally paired serum samples for biomarkers and echocardiograms in a prospective multicenter cohort study of PHIV a ...[more]

PMID: 29596110

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Project description:BackgroundHIV infection and its management confer a substantial health burden to affected individuals and have been associated with increased risk of oral and dental diseases. In this study, we sought to quantify HIV-associated differences in the prevalence and severity of dental caries in the primary and permanent dentition of 4-11-year-old Nigerian Children.MethodsWe used clinical, laboratory, demographic, and behavioral data obtained from an ongoing cohort study of age-matched HIV-infected (HI, n = 181), HIV-exposed-but-uninfected (HEU, n = 177), and HIV-unexposed-and-uninfected (HUU, n = 186) children. Measures of dental caries experience (i.e., prevalence and severity) were based on dmft/DMFT indices recorded by trained and calibrated clinical examiners. Differences in primary and permanent dentition caries experience between HI, HEU, and HUU were estimated using multivariable logistic and negative binomial regression modeling.ResultsHI children had significantly higher caries experience (33%) compared to HEU (15%) and HUU (22%) children. This difference persisted in fully adjusted analyses [odds ratio (OR) = 1.6; 95% confidence interval (CI) = 1.0-2.6], was most pronounced in the permanent dentition (OR = 3.4; 95% CI = 1.2-9.5), and mirrored differences in caries severity. While molars were predominantly affected in both primary and permanent dentitions, caries lesion patterns differed between dentitions. Caries severity was significantly associated with hypoplastic primary teeth, gingival inflammation, and lower CD4 counts.ConclusionsWe found that the higher prevalence and severity of dental caries among HI children was driven by increased burden of permanent dentition caries compared to their uninfected counterparts. The dentition-specific associations identified in this study highlight the need to design and implement age-specific caries prevention strategies. These may include intensified oral hygiene regimens aimed at mitigating the cariogenic impact of hyposalivation among HI children. Similarly, the long-lasting impacts of developmental defects of the enamel in the primary and permanent dentitions must not be ignored.

Project description:Highly active antiretroviral treatment (HAART) has greatly reduced opportunistic infections in HIV-infected individuals. However, even with the use of HAART, HIV-infected individuals are still at an increased risk of oral diseases, including dental caries. Dental caries development is associated with microbial community shifts leading to community dysbiosis. HIV infection can significantly alter the bacteriome and mycobiome composition in the oral cavity; however, these impacts have not been assessed for caries initiation and progression. The aim of this study was to characterize the mycobiome for supragingival plaque samples from HIV-infected (HI), HIV-exposed-but-uninfected (HEU), and HIV-unexposed-and-uninfected (HUU) children with and without caries. To accomplish this, ITS1 amplicons of 127 samples were sequenced. We found that HIV infection and exposure resulted in changes to the supragingival plaque mycobiome for both health and caries. Overall, a reduction in community diversity as caries progressed was observed, with HI children having the lowest diversity and HEU children the highest. Candida albicans was the most abundant species identified, with 177 different amplicon sequence variants (ASVs). Two C. albicans ASVs dominated the data (53.0% and 38.5% of all taxonomic assignments). The more frequent ASV dominated HI and HUU communities, whereas the second dominated HEU communities. HEU children also had the lowest abundance of C. albicans and the highest number of health-associated taxa (taxa statistically associated with caries-free teeth).IMPORTANCEGlobally, caries is among the most frequent chronic childhood disease, and the fungal component of the microbial community responsible is poorly studied despite evidence that fungi contribute to increased acid production exacerbating enamel demineralization. HIV infection is another global health crisis. Perinatal HIV exposure with infection are caries risk factors; however, the caries experience in the context of perinatal HIV exposure without infection is less clear. Using high-throughput amplicon sequencing, we find taxonomic differences that become pronounced during late-stage caries. Notably, we show a stronger correlation with health-associated taxa for HIV-exposed-but-uninfected children when compared to unexposed and uninfected children. This aligns with a lower incidence of caries in primary teeth at age 6 or less for exposed yet uninfected children. Ultimately, these findings could contribute to improved risk assessment, intervention, and prevention strategies such as biofilm disruption and the informed design of pro-, pre-, and synbiotic oral therapies.

Dataset Information

Cardiac and inflammatory biomarkers in perinatally HIV-infected and HIV-exposed uninfected children.

Publications

Cardiac and inflammatory biomarkers in perinatally HIV-infected and HIV-exposed uninfected children.

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