Adenosine Deaminase as a Biomarker of Tenofovir Mediated Inflammation in Naïve HIV Patients

Conesa-Buendía, Francisco Miguel; Llamas-Granda, Patricia; Atencio, Patricia; Cabello, Alfonso; Górgolas, Miguel; Largo, Raquel; Herrero‐Beaumont, Gabriel; Mediero, Aránzazu

doi:10.3390/ijms21103590

Cited by 4 publications

(4 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…TDF has been repeatedly associated with its toxic effect on bone. TDF directly interferes with bone homeostasis through the reduction of extracellular adenosine levels, mediated by inhibition of ATP release from cells ( 11 , p.; 12 ). As a result, there is a stimulation of osteoclast differentiation and osteoblast inhibition, with increased bone resorption.…”

Section: Discussionmentioning

confidence: 99%

Changes in bone quality after switching from a TDF to a TAF based ART: A pilot randomized study

et al. 2023

View full text Add to dashboard Cite

BackgroundThe impact of tenofovir disoproxil fumarate (TDF) antiretroviral (ART) regimens on bone health has been characterized mostly by bone mineral density (BMD), but recently also by bone quality (BQ). The aim of this pilot study is to assess the changes in BMD and BQ after switch from TDF to tenofovir alafenamide (TAF) ART.MethodsHIV individuals receiving TDF-based ART were randomized to switch to Bictegravir-TAF-Emtricitabine or to remain in the same regimen. At baseline and 24-weeks after randomization, participants underwent bone mineral density (BMD) by DXA and BQ assessment using bone microindentation, a validated technique that measures bone tissue quality expressed as bone material strength index (BMSi). A panel of plasma bone turnover biomarkers were measured by ELISA at the same time-points. Values are expressed as median [interquartile range] and non-parametric tests were used where appropriate.ResultsA total of 24 HIV individuals were included in the study, 19 of which were men (80%). Median age at baseline was 43 years (IQR 38-54). Half of individuals were allocated in the TDF group while the other half changed to TAF treatment. No differences at baseline between both groups were detected in any parameter. Non-significant changes nor in lumbar or femoral BMD at week 24 was found in any regimen. In contrast, there was an increase in BMSi in the TAF arm at 24 weeks, and thus an improvement in BQ[81.6 (79-83) to 86 (80-88) (+5.1%);p=0.041], whereas the TDF arm remained stable from 82 (76-85) at baseline to 82 (73-83);p=0.812. Hence, at week 24 there were significant differences in BQ between arms (p=0.049). A reduction in bone formation markers was found at week 24 in both regimens: N-terminal propeptide of type-1 collagen decreased a 20% (-35 - -0.6); p=0.031 with TAF and -16% (-25 - -5); p=0.032 with TDF. Also a decrease in bone resorption marker C-telopeptide with TAF was detected [-10% (-19 - -5);p=0.028] but not with TDF (p=0.232), suggesting a less metabolically active bone after switching to TAF.ConclusionA bone quality improvement was found after switching from a TDF to a TAF based ART independently of BMD, suggesting that the bone health benefits of TAF may extend beyond BMD. Future research should be directed to confirm these findings and to identify the underlying mechanisms of ART related bone toxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Changes in bone quality after switching from a TDF to a TAF based ART: A pilot randomized study

et al. 2023

View full text Add to dashboard Cite

show abstract

“…GEE significance was calculated from the Wald statistic after performing deviance analysis against a null model (54). Comparisons between demographic and physiological variables like biological sex, heart rate, and gestational or maternal age were analyzed using untransformed data (U/L) and rank sum Wilcoxon and Kruskal-Wallis tests (55) to allow for comparison with previously published data (3,(56)(57)(58)(59)(60) and hospital-based tests on absolute plasma ADA1, ADA2, and total ADA concentrations. For tables and graphs presenting absolute activity concentrations, the median and the interquartile range (IQR) were used for descriptive statistics (61).…”

Section: Methodsmentioning

confidence: 99%

Plasma Adenosine Deaminase (ADA)-1 and -2 Demonstrate Robust Ontogeny Across the First Four Months of Human Life

et al. 2021

View full text Add to dashboard Cite

BackgroundHuman adenosine deaminases (ADAs) modulate the immune response: ADA1 via metabolizing adenosine, a purine metabolite that inhibits pro-inflammatory and Th1 cytokine production, and the multi-functional ADA2, by enhancing T-cell proliferation and monocyte differentiation. Newborns are relatively deficient in ADA1 resulting in elevated plasma adenosine concentrations and a Th2/anti-inflammatory bias compared to adults. Despite the growing recognition of the role of ADAs in immune regulation, little is known about the ontogeny of ADA concentrations.MethodsIn a subgroup of the EPIC002-study, clinical data and plasma samples were collected from 540 Gambian infants at four time-points: day of birth; first week of life; one month of age; and four months of age. Concentrations of total extracellular ADA, ADA1, and ADA2 were measured by chromogenic assay and evaluated in relation to clinical data. Plasma cytokines/chemokine were measured across the first week of life and correlated to ADA concentrations.ResultsADA2 demonstrated a steady rise across the first months of life, while ADA1 concentration significantly decreased 0.79-fold across the first week then increased 1.4-fold by four months of life. Males demonstrated significantly higher concentrations of ADA2 (1.1-fold) than females at four months; newborns with early-term (37 to <39 weeks) and late-term (≥41 weeks) gestational age demonstrated significantly higher ADA1 at birth (1.1-fold), and those born to mothers with advanced maternal age (≥35 years) had lower plasma concentrations of ADA2 at one month (0.93-fold). Plasma ADA1 concentrations were positively correlated with plasma CXCL8 during the first week of life, while ADA2 concentrations correlated positively with TNFα, IFNγ and CXCL10, and negatively with IL-6 and CXCL8.ConclusionsThe ratio of plasma ADA2/ADA1 concentration increased during the first week of life, after which both ADA1 and ADA2 increased across the first four months of life suggesting a gradual development of Th1/Th2 balanced immunity. Furthermore, ADA1 and ADA2 were positively correlated with cytokines/chemokines during the first week of life. Overall, ADA isoforms demonstrate robust ontogeny in newborns and infants but further mechanistic studies are needed to clarify their roles in early life immune development and the correlations with sex, gestational age, and maternal age that were observed.

show abstract

“…В работах ряда исследователей показано, что у пациентов с ВИЧ-инфекцией, получающих АРВТ, уровни активности АДА в сыворотке и плазме остаются повышенными, хотя и в меньшей степени, что может быть объяснено ко-инфекциями, антиретровирусной токсичностью или просто стойким воспалением и иммунной активацией, вызванными остаточной репликацией вируса, присутствующей даже при успешном лечении [27,28]. Полученную нами статистически значимо высокую активность общей АДА и АДА-2 у больных с туберкулезным плевритом и ВИЧ-инфекцией, получающих АРВТ, вероятно, можно объяснить тем, что при антиретровирусной терапии ответ АДА зависит как от предшествующего истощения CD4 + Т-клеток, так и от препаратов антиретровирусной терапии [29,30].…”

unclassified

Enzymes of purine metabolism — biomarkers for the diagnostics of tuberculous pleurisy in patients with HIV infection

Dyakova

Vladimirov

Esmedlyaeva

et al. 2023

VIČ-infekc. immunosupr.

View full text Add to dashboard Cite

The objective of the study was to evaluate the information content of determining the activity of adenosine deaminase and adenosine deaminase-2 in the diagnosis of tuberculous pleurisy in patients with HIV infection.Materials and methods. A total of 378 patients with pleural effusion were retrospectively examined. In 215 cases, tuberculous pleurisy was detected (TP); and 163 patients had non-tuberculous pleural effusion (non-TP). As much as 27 patients in the TP group were HIV co-infected (TP/HIV+), the remaining 188 patients were HIV — negative (TP/HIV–). In all the patients, the activity of total adenosine deaminase (ADA) and its isoenzymes (ADA-1 and ADA-2) in the pleural fluid was determined.Results and discussion. In the TP group, the activity of total ADA (95.5 [67.7; 115.4] versus 82.0 [59.6; 100.0] U/L, p=0.1), ADA-1 (14.2 [5.8; 20.5] versus 12.1 [6.1; 23.7] U/L, p=0.9) and ADA-2 (78,1 [38.1; 93.1] versus 62.4 [35.4; 82.2] U/L, p=0,1) did not depend on HIV status. The activity of these indicators was determined above the threshold level — total ADA in 96.3% and 95.2%, ADA-1 in 25.9% and 30.8% and ADA-2 in 92.6% and 83.3% of cases in the «TP/HIV+» and «TP/HIV–» groups, respectively. A negative correlation between ADA-1 activity and HIV viral load in the group of patients with tuberculous pleurisy and HIV infection (r=–0.45; p=0.008), as well as in the subgroup of TP/HIV+ patients who received (r=–0.9; p=0.008) and in those who didn’t receive ART (r=–0.47; p=0.04) was obtained. Our results show that a total ADA activity increase in the patients with tuberculous pleurisy, regardless of patients’ HIV status, occur due to ADA-2. Thus, the increase in activity of total ADA and ADA-2 in our study was caused by active tuberculosis, not by the presence or absence of HIV co-infection. Also, the ADA-2 activity in HIV-infected patients is likely consistent with ADA-2 important role in cellular immune responses.Conclusion. Our data indicate the participation of purine metabolism enzymes in the pathogenesis of HIV infection. At the same time, adenosine deaminase activity is not a specific biomarker of individual changes characteristic of HIV infection. The study results suggest that the total adenosine deaminase and adenosine deaminase-2 activity increase is a valuable and diagnostically significant marker of tuberculous pleurisy in HIV-infected patients. The value of adenosine deaminase and adenosine deaminase-2 activity remains high even in the patients having severe immunosuppression, which allows them to be actively used for rapid diagnostics and hence, early TB therapy initiation.

show abstract

Adenosine Deaminase as a Biomarker of Tenofovir Mediated Inflammation in Naïve HIV Patients

Cited by 4 publications

References 59 publications

Changes in bone quality after switching from a TDF to a TAF based ART: A pilot randomized study

Changes in bone quality after switching from a TDF to a TAF based ART: A pilot randomized study

Plasma Adenosine Deaminase (ADA)-1 and -2 Demonstrate Robust Ontogeny Across the First Four Months of Human Life

Enzymes of purine metabolism — biomarkers for the diagnostics of tuberculous pleurisy in patients with HIV infection

Contact Info

Product

Resources

About