Persistent metabolic changes in HIV-infected patients during the first year of combination antiretroviral therapy

Peltenburg, N. Chantal; Schoeman, Johannes C.; Hou, Jun; Mora, Fernando; Harms, Amy C.; Lowe, Selwyn H.; Bierau, Jörgen; Bakker, J.; Verbon, Annelies; Hankemeier, Thomas; Boonstra, André

doi:10.1038/s41598-018-35271-0

Cited by 50 publications

(62 citation statements)

References 57 publications

(57 reference statements)

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“…Dillon et al and Brenchley et al stated that the altered microbiome is associated with systemic inflammation; these findings may be the reason for altered metabolism [38,39]. Peltenburg et al have found impaired biogenic amine levels in an untreated HIV(+) patient group [40]. Metabolic dysregulation was also common in this study; biogenic amine disturbances may have a role in the metabolic effects of HIV as well.…”

Section: Discussionsupporting

confidence: 56%

HIV, Antiretroviral Therapy and Metabolic Alterations: A Review

Ergin¹,

Inga²,

Maung³

et al. 2020

Cureus

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The introduction of antiretroviral therapy (ART) has caused some metabolic problems to people who suffer from HIV. ART probably is not the sole reason for these metabolic disorders. Most likely, HIV itself affects the metabolism as well. We conducted research to find the prevalence of the different types of metabolic disorders among HIV(+) patients. Female gender, high BMI, and older age are among the risk factors for the occurrence of metabolic disorders. Regarding dyslipidemia, hypertriglyceridemia and low high-density lipoproteins (HDLs) are the most common types of dyslipidemia in the studies we included. Protease inhibitors (PIs) are widely known as the most common class of antiretroviral drugs that cause metabolic disorders, and some studies in our review also demonstrated this knowledge. In our review, we concluded that HIV and ART concurrently alter the metabolism, but further research is required about this substantial topic.

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Section: Discussionsupporting

confidence: 56%

HIV, Antiretroviral Therapy and Metabolic Alterations: A Review

Ergin¹,

Inga²,

Maung³

et al. 2020

Cureus

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“…The use of ART to control HIV-1 has been associated with a number of cellular changes [44][45][46][47]. Since EpKS patients in our cohort had varying ART duration and some with detectable plasma HIV-1 viral load despite ART treatment, we tested the effect of ART duration and HIV-1 viremia on EpKS transcriptome profiles.…”

Section: Plos Pathogensmentioning

confidence: 99%

“…Whether the same dysregulations, or similar magnitude of changes, occur in EnKS, has not been investigated. Because lipid metabolic dysregulation is common in ART treated HIV-1 infected individuals [44][45][46][47], it will be important to determine whether the KS-associated lipid metabolism defects are due to KSHV infection, attributable to HIV-1 co-infection or result from ART. Moreover, a male gender bias in KS has been noted, especially for classical and EnKS, suggesting a potential involvement of androgens or androgen receptors in the disease pathogenesis [48][49][50][51][52].…”

Section: Introductionmentioning

confidence: 99%

Comparative transcriptome analysis of endemic and epidemic Kaposi’s sarcoma (KS) lesions and the secondary role of HIV-1 in KS pathogenesis

et al. 2020

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In sub-Saharan Africa, endemic Kaposi's sarcoma (EnKS) is still prevalent despite high incidence of epidemic Kaposi's sarcoma (EpKS) resulting from the ongoing HIV-1 epidemic. While KSHV is clearly the etiologic agent of KS, the mechanisms underlying KS development are not fully understood. For example, HIV-1 co-infection and concomitant immune dysfunction have been associated with EpKS development. However, the direct or indirect role(s) of HIV-1, and therefore of immune suppression, in EpKS remains unclear. How, or whether, EpKS is mechanistically distinct from EnKS is unknown. Thus, the absence of HIV-1 co-infection in EnKS provides a unique control for investigating and deciphering whether HIV-1 plays a direct or indirect role in the EpKS tumor microenvironment. We hypothesized that HIV-1 co-infection would induce transcriptome changes that differentiate EpKS from EnKS, thereby defining the direct intra-tumor role of HIV-1 in KS. Comparison of ARTtreated and-naïve patients would further define the impact of ART on the KS transcriptome. We utilized RNA-seq followed by multiparameter bioinformatics analysis to compare transcriptomes from KS lesions to uninvolved control skin. We provide the first transcriptomic comparison of EpKS versus EnKS, ART-treated vs-naïve EpKS and male vs female EpKS to define the roles of HIV-1 co-infection, the impact of ART, and gender on KS gene expression profiles. Our findings suggest that ART-use and gender have minimal impact on transcriptome profiles of KS lesions. Gene expression profiles strongly correlated between EpKS and EnKS patients (Spearman r = 0.83, p<10 −10). A subset of genes involved in tumorigenesis and inflammation/immune responses showed higher magnitude, but not unique dysregulation in EnKS compared to EpKS. While gender and ART had no detectable contribution, the trend toward higher magnitude of gene dysregulation in EnKS coupled with

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“… The Bio-Plex® 200 system Luminex analyser, Bio-Rad, CA, USA Plasma inflammation and cell stress biomarkers : In a subgroup of MIPs with different durations of exposures to ART from pregnancy to 12 months of age At least 25 inflammatory chemokines and cytokines measurements. The Bio-Plex® 200 system Luminex analyser, Bio-Rad, CA USA Plasma metabolomics: > 400 analytes, in a subgroup of MIPs with different durations of exposures to ART from pregnancy to 12 months of age to assess altered amino acid and lipid metabolism 3 platforms -Biogenic amines (Amino acids, catecholamines & polyamines), Signalling lipids (Sphingosine-1-phosphate etc., Positive lipids (Lysophospholipids, phospholipids, cholesterol esters, di/triglycerides & sphingomyelins) as described [ 76 ]. UPLC; TQMS; QToF –HPLC; UHPLC –; MS/MS – Triple Quadrupole Mass Spectrometer.…”

Section: Methodsmentioning

confidence: 99%

“…-Biogenic amines (Amino acids, catecholamines & polyamines), Signalling lipids (Sphingosine-1-phosphate etc., Positive lipids (Lysophospholipids, phospholipids, cholesterol esters, di/triglycerides & sphingomyelins) as described [ 76 ].…”

Section: Methodsmentioning

confidence: 99%

The University of Zimbabwe College of Health Sciences (UZ-CHS) BIRTH COHORT study: rationale, design and methods

Duri

Gumbo²,

Munjoma

et al. 2020

BMC Infect Dis

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Background Commencing lifelong antiretroviral therapy (ART) immediately following HIV diagnosis (Option B+), has greatly improved maternal-infant health. Thus, large and increasing numbers of HIV-infected women are on ART during pregnancy, a situation concurrently increasing numbers of HIV-exposed-uninfected (HEU) infants. Compared to their HIV-unexposed-uninfected (HUU) counterparts, HEU infants show higher rates of adverse birth outcomes, mortality, infectious/non-communicable diseases including impaired growth and neurocognitive development. There is an urgent need to understand the impact of HIV and early life ART exposures, immune-metabolic dysregulation, comorbidities and environmental confounders on adverse paediatric outcomes. Methods Six hundred (600) HIV-infected and 600 HIV-uninfected pregnant women ≥20 weeks of gestation will be enrolled from four primary health centres in high density residential areas of Harare. Participants will be followed up as mother-infant-pairs at delivery, week(s) 1, 6, 10, 14, 24, 36, 48, 72 and 96 after birth. Clinical, socio-economic, nutritional and environmental data will be assessed for adverse birth outcomes, impaired growth, immune/neurodevelopment, vertical transmission of HIV, hepatitis-B/C viruses, cytomegalovirus and syphilis. Maternal urine, stool, plasma, cord blood, amniotic fluid, placenta and milk including infant plasma, dried blood spot and stool will be collected at enrolment and follow-up visits. The composite primary endpoint is stillbirth and infant mortality within the first two years of life in HEU versus HUU infants. Maternal mortality in HIV-infected versus -uninfected women is another primary outcome. Secondary endpoints include a range of maternal and infant outcomes. Sub-studies will address maternal stress and malnutrition, maternal-infant latent tuberculosis, Helicobacter pylori infections, immune-metabolomic dysregulation including gut, breast milk and amniotic fluid dysbiosis. Discussion The University of Zimbabwe-College of Health-Sciences-Birth-Cohort study will provide a comprehensive assessment of risk factors and biomarkers for HEU infants’ adverse outcomes. This will ultimately help developing strategies to mitigate effects of maternal HIV, early-life ART exposures and comorbidities on infants’ mortality and morbidity. Trial registration ClinicalTrial.gov Identifier: NCT04087239. Registered 12 September 2019.

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Persistent metabolic changes in HIV-infected patients during the first year of combination antiretroviral therapy

Cited by 50 publications

References 57 publications

HIV, Antiretroviral Therapy and Metabolic Alterations: A Review

HIV, Antiretroviral Therapy and Metabolic Alterations: A Review

Comparative transcriptome analysis of endemic and epidemic Kaposi’s sarcoma (KS) lesions and the secondary role of HIV-1 in KS pathogenesis

The University of Zimbabwe College of Health Sciences (UZ-CHS) BIRTH COHORT study: rationale, design and methods

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