Soluble CD14, CD163, and CD27 biomarkers distinguish ART-suppressed youth living with HIV from healthy controls

Williams, Julie C.; Zhang, Xinrui; Karki, Manju; Chi, Yueh‐Yun; Wallet, Shannon M.; Rudy, Bret J.; Nichols, Sharon L.; Goodenow, Maureen M.; Sleasman, John W.

doi:10.1002/jlb.3a0717-294rr

Cited by 25 publications

(22 citation statements)

References 40 publications

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“…Contradictory results have been reported from different studies on the effect of cART on sCD14 (33–35) due to a variety of contributors (36, 37). On the other hand, sCD163, a marker of vascular inflammation (38) and neurocognitive impairment (39), was higher in PLHIV than in healthy controls, which is in contrast to previous reports (40) but in line with other studies which showed that sCD163 was higher compared to the HIV-negative controls within 2 years of therapy (41, 42). The novelty of our study was to explore a large panel of inflammatory markers and we showed significantly higher levels of MMP1 (43), ADA (44), CD8A (16), SLAMF1 (45), and CCL23 (46) in PLHIV on long term ART.…”

Section: Discussionsupporting

confidence: 67%

Systemic Inflammation and the Increased Risk of Inflamm-Aging and Age-Associated Diseases in People Living With HIV on Long Term Suppressive Antiretroviral Therapy

et al. 2019

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The ART program in low- and middle-income countries (LMIC) like India, follows a public health approach with a standardized regimen for all people living with HIV (PLHIV). Based on the evidence from high-income countries (HIC), the risk of an enhanced, and accentuated onset of premature-aging or age-related diseases has been observed in PLHIV. However, very limited data is available on residual inflammation and immune activation in the populations who are on first-generation anti-HIV drugs like zidovudine and lamivudine that have more toxic side effects. Therefore, the aim of the present study was to evaluate the levels of systemic inflammation and understand the risk of age-associated diseases in PLHIV on long-term suppressive ART using a large number of biomarkers of inflammation and immune activation. Blood samples were obtained from therapy naïve PLHIV (Pre-ART, n = 43), PLHIV on ART for >5 years (ART, n = 53), and HIV-negative healthy controls (HIVNC, n = 41). Samples were analyzed for 92 markers of inflammation, sCD14, sCD163, and telomere length. Several statistical tests were performed to compare the groups under study. Multivariate linear regression was used to investigate the associations. Despite a median duration of 8 years of successful ART, sCD14 ( p < 0.001) and sCD163 ( p = 0.04) levels continued to be significantly elevated in ART group as compared to HIVNC. Eleven inflammatory markers, including 4E-BP1, ADA, CCL23, CD5, CD8A, CST5, MMP1, NT3, SLAMF1, TRAIL, and TRANCE, were found to be significantly different ( p < 0.05) between the groups. Many of these markers are associated with age-related co-morbidities including cardiovascular disease, neurocognitive decline and some of these markers are being reported for the first time in the context of HIV-induced inflammation. Linear regression analysis showed a significant negative association between HIV-1-positivity and telomere length ( p < 0.0001). In ART-group CXCL1 ( p = 0.048) and TGF-α ( p = 0.026) showed a significant association with the increased telomere length and IL-10RA was significantly associated with decreased telomere length ( p = 0.042). This observation warrants further mechanistic studies to generate evidence to highlight the need for enhanced treatment monitoring and special interventions in HIV-infected individuals.

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Section: Discussionsupporting

confidence: 67%

Systemic Inflammation and the Increased Risk of Inflamm-Aging and Age-Associated Diseases in People Living With HIV on Long Term Suppressive Antiretroviral Therapy

et al. 2019

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“…Our findings are consistent with those of previous studies that, in mainly chronically-infected patients, compared treated PLHIV to appropriate controls [ 11 , 18 , 21 ]. Interestingly, a recent study from the MACS cohort reported abnormally elevated concentrations of certain inflammatory biomarkers including sCD14, sTNFRII, but also CXCL10 and TNF-α, even in MSM who reported 100% ART adherence [22] .…”

Section: Discussionsupporting

confidence: 93%

“…Interestingly, a recent study from the MACS cohort reported abnormally elevated concentrations of certain inflammatory biomarkers including sCD14, sTNFRII, but also CXCL10 and TNF-α, even in MSM who reported 100% ART adherence [22] . sCD14 and sCD163 have been identified several times as the markers that best discriminated between HIV-infected and uninfected individuals [ 11 , 18 , 21 ]. In an older population, with a median age 59 years, Booiman et al did not observe any difference in sCD14 according to HIV status, but still reported elevated levels of sCD163 and I-FABP in PLHIV after a median of eight years of ART [10] .…”

Section: Discussionmentioning

confidence: 99%

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Persistence of monocyte activation under treatment in people followed since acute HIV-1 infection relative to participants at high or low risk of HIV infection

et al. 2020

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Background Interpretation of the increase in certain inflammatory markers in virally suppressed HIV-infected individuals must rely on an appropriate uninfected control group well characterized for non-HIV-related factors that contribute to chronic inflammation, e.g. smoking, alcohol consumption, or being overweight. We compared the inflammatory profiles of HIV-infected participants under long-term antiretroviral therapy (ART) with those of two HIV-uninfected groups with contrasting health behaviours. Methods We studied 150 HIV-infected participants (42 women, 108 men) under long-term ART (median, 6 years) followed in the ANRS PRIMO cohort since acute/early HIV-1 infection (AHI) diagnosis. Sex and age-matched controls were sampled from i) the ANRS IPERGAY pre-exposure prophylaxis trial among men at high risk for HIV infection and with high frequencies of non-HIV factors of inflammation ii) the ANRS COHVAC cohort of volunteers in vaccine trials with a low-risk profile for HIV infection . We measured the plasma levels of ten inflammatory markers. Findings After adjusting for smoking, alcohol use and body mass index, both HIV-infected men and women had higher levels of sCD14, sCD163, sTNFRII and I-FABP than their high-risk IPERGAY and low-risk COHVAC counterparts. Hierarchical clustering showed a subset of 15 PRIMO participants to have an inflammatory profile similar to that of most HIV-negative participants. These participants already had favourable markers at AHI diagnosis. Interpretation Long-term ART, even when initiated at a low level of immunodeficiency, fails to normalize monocyte/macrophage activation and gut epithelial dysfunction. Persistent inflammation under treatment may be related to an increased inflammatory profile since AHI. Funding ANRS and Paris-Saclay University.

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“…Finally, plasma levels of IP-10, sCD14, and sCD163 were measured. These molecules have been proposed as markers of persistent inflammation in HIV infection since their levels remain elevated despite years of cART, compared to healthy donors [30][31][32][33][34][35][36][37]. Both IP-10, sCD14, and sCD163 were detected in all the samples tested.…”

Section: Cohort Description and Experimental Determinationsmentioning

confidence: 96%

Pre-cART Immune Parameters in People Living With HIV Might Help Predict CD8+ T-Cell Characteristics, Inflammation Levels, and Reservoir Composition After Effective cART

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Trifone

et al. 2021

PAI

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Background: Combined antiretroviral treatment (cART) for HIV infection is highly effective in controlling viral replication. However, it cannot achieve a sterilizing cure. Several strategies have been proposed to achieve a functional cure, some of them based on immune-mediated clearing of persistently infected cells. Here, we aimed at identifying factors related to CD8TC and CD4TC quality before cART initiation that associate with the persistence of CD8TC antiviral response after cART, inflammation levels, and the size of the viral reservoir. Methods: Samples from 25 persons living with HIV were obtained before and after (15 months) cART initiation. Phenotype and functionality of bulk and HIV-specific T cells were assayed by flow cytometry ex vivo or after expansion in pre-cART or post-cART samples, respectively. Cell-Associated (CA) HIV DNA (total and integrated) and RNA (unspliced [US] and multiple spliced [MS]) were quantitated by real-time PCR on post-cART samples. Post-cART plasma levels of CXCL10 (IP-10), soluble CD14 (sCD14) and soluble CD163 (sCD163) were measured by ELISA. Results: Pre-cART phenotype of CD8TCs and magnitude and phenotype of HIV-specific response correlated with the phenotype and functionality of CD8TCs post-cART. Moreover, the phenotype of the CD8TCs pre-cART correlated with markers of HIV persistence and inflammation post-cART. Finally, exhaustion and differentiation of CD4TCs pre-cART were associated with the composition of the HIV reservoir post-cART and the level of inflammation. Conclusions: Overall, this work provides data to help understand and identify parameters that could be used as markers in the development of immune-based functional HIV cure strategies.

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Soluble CD14, CD163, and CD27 biomarkers distinguish ART-suppressed youth living with HIV from healthy controls

Abstract: Soluble inflammatory and lymphocyte biomarkers sufficiently distinguish YLWH from HC. Persistent macrophage activation biomarkers may provide a means to monitor consequences of HIV infection in fully suppressed YLWH.

Cited by 25 publications

References 40 publications

Systemic Inflammation and the Increased Risk of Inflamm-Aging and Age-Associated Diseases in People Living With HIV on Long Term Suppressive Antiretroviral Therapy

Systemic Inflammation and the Increased Risk of Inflamm-Aging and Age-Associated Diseases in People Living With HIV on Long Term Suppressive Antiretroviral Therapy

Persistence of monocyte activation under treatment in people followed since acute HIV-1 infection relative to participants at high or low risk of HIV infection

Pre-cART Immune Parameters in People Living With HIV Might Help Predict CD8+ T-Cell Characteristics, Inflammation Levels, and Reservoir Composition After Effective cART

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