scholarly journals A Link Between Methylglyoxal and Heart Failure During HIV-1 Infection

2021 ◽  
Vol 8 ◽  
Author(s):  
Prasanta K. Dash ◽  
Fadhel A. Alomar ◽  
Jesse L. Cox ◽  
JoEllyn McMillan ◽  
Bryan T. Hackfort ◽  
...  
Keyword(s):  
Heart Failure ◽  
Hiv Infection ◽  
Post Infection ◽  
Fold Increase ◽  
Causal Link ◽  
Cardiac Tissues ◽  
Viral Loads ◽  
Microvascular Leakage ◽  
Biochemical Analyses ◽  
Hiv 1

Early-onset heart failure (HF) continues to be a major cause of morbidity and mortality in people living with human immunodeficiency virus type one (HIV-1) infection (PLWH), yet the molecular causes for this remain poorly understood. Herein NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ humanized mice (Hu-mice), plasma from PLWH, and autopsied cardiac tissues from deceased HIV seropositive individuals were used to assess if there is a link between the glycolysis byproduct methylglyoxal (MG) and HF in the setting of HIV-1 infection. At five weeks post HIV infection, Hu-mice developed grade III-IV diastolic dysfunction (DD) with an associated two-fold increase in plasma MG. At sixteen-seventeen weeks post infection, cardiac ejection fraction and fractional shortening also declined by 26 and 35%, and plasma MG increased to four-fold higher than uninfected controls. Histopathological and biochemical analyses of cardiac tissues from Hu-mice 17 weeks post-infection affirmed MG increase with a concomitant decrease in expression of the MG-degrading enzyme glyoxalase-1 (Glo1). The endothelial cell marker CD31 was found to be lower, and coronary microvascular leakage and myocardial fibrosis were prominent. Increasing expression of Glo1 in Hu-mice five weeks post-infection using a single dose of an engineered AAV2/9 (1.7 × 1012 virion particles/kg), attenuated the increases in plasma and cardiac MG levels. Increasing Glo1 also blunted microvascular leakage, fibrosis, and HF seen at sixteen weeks post-infection, without changes in plasma viral loads. In plasma from virally suppressed PLWH, MG was also 3.7-fold higher. In autopsied cardiac tissues from seropositive, HIV individuals with low viral log, MG was 4.2-fold higher and Glo1 was 50% lower compared to uninfected controls. These data show for the first time a causal link between accumulation of MG and HF in the setting of HIV infection.

CD4+ T cell count, HIV-1 viral loads and demographic variables of newly identified patients with HIV infection in Wuhan, China

2013 ◽  
Vol 85 (10) ◽  
pp. 1687-1691 ◽  
Author(s):  
Man-Qing Liu ◽  
Li Tang ◽  
Wen-Hua Kong ◽  
Ze-Rong Zhu ◽  
Jin-Song Peng ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
Cell Count ◽  
Demographic Variables ◽  
Cd4 T Cell ◽  
Viral Loads ◽  
Hiv 1 ◽  
Cd4 T Cell Count

scholarly journals The Association Between HIV Infection and the Use of Palliative Care in Patients Hospitalized With Heart Failure

2018 ◽  
Vol 36 (3) ◽  
pp. 228-234
Author(s):  
Shelli L. Feder ◽  
Janet P. Tate ◽  
Kathleen M. Akgün ◽  
Julie A. Womack ◽  
Sangchoon Jeon ◽  
...  
Keyword(s):  
Heart Failure ◽  
Palliative Care ◽  
Hiv Infection ◽  
Primary Diagnosis ◽  
Left Ventricular ◽  
Hospitalized Patients ◽  
Left Ventricular Ejection ◽  
Cd4 Counts ◽  
Independent Variables ◽  
Hiv 1

Background: The number of adults with heart failure (HF) and HIV infection is increasing. These patients may benefit from palliative care (PC). Objectives: Determine the association between HIV infection, other HIV characteristics, and PC among hospitalized patients with HF in the Veterans Health Administration (VHA). Design: Nested case–control study of patients with HF hospitalized from 2003 to 2015 and enrolled in the Veterans Aging Cohort Study. Setting/Patients: Two hundred and ten hospitalized patients with HF who received PC matched to 1042 patients with HF who did not receive PC, by age, discharge date, and left ventricular ejection fraction. Measurements: Palliative care use was the primary outcome. Independent variables included HIV infection identified by International Classification of Diseases Ninth Revision code and further characterized as the primary diagnosis for hospitalization, unsuppressed HIV-1 RNA, CD4 counts <200 cells/mm3, and other covariates. We examined associations between independent variables and PC using conditional logistic regression. Results: The sample was 99% male, mean age was 64 years (standard deviation ±10), 54% of cases and 59% of controls were black, and 30% of cases and 31% of controls were HIV-infected. In adjusted models, HIV as the primary diagnosis for hospitalization (odds ratio [OR]: 3.69, 95% confidence interval [CI]: 1.30-10.52), unsuppressed HIV-1 RNA (OR: 2.62, 95% CI: 1.31-5.24), and CD4 counts <200 cells/mm3 (OR: 3.47; 1.78-6.77), but not HIV infection (OR: 0.79, 95% CI: 0.55-1.13), were associated with PC. Conclusions: HIV characteristics indicative of severe disease are associated with PC for hospitalized VHA patients with HF. Increasing access to PC for patients with HF and HIV is warranted.

scholarly journals Sex dependent Vulnerability of Fetal Nonhuman Primate Cardiac Mitochondria to Moderate Maternal Nutrient Reduction

2021 ◽  
Author(s):  
Susana P. Pereira ◽  
Ludgero C. Tavares ◽  
Ana I. Duarte ◽  
Inês Baldeiras ◽  
Teresa Cunha-Oliveira ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Dysfunction ◽  
Fetal Development ◽  
Maternal Nutrition ◽  
Fold Increase ◽  
Later Life ◽  
Maternal Plasma ◽  
Nutrient Reduction ◽  
Cardiac Tissues ◽  
Sufficient Energy

Poor maternal nutrition in pregnancy affects fetal development, predisposing offspring to cardiometabolic diseases. The role of mitochondria during fetal development on later-life cardiac dysfunction caused by maternal nutrient reduction (MNR) remains unexplored. We hypothesized that MNR during gestation causes fetal cardiac bioenergetic deficits, compromising cardiac mitochondrial metabolism and reserve capacity. To enable human translation, we developed a primate baboon model (Papio spp) of moderate MNR in which mothers receive 70% of control nutrition during pregnancy, resulting in intrauterine growth restriction (IUGR) offspring and later exhibiting myocardial remodeling and heart failure at human equivalent ~25years. Term control and MNR baboon offspring were necropsied following cesarean-section, and left ventricle (LV) samples were collected. MNR adversely impacted fetal cardiac LV mitochondria in a sex-dependent fashion. Increased maternal plasma aspartate aminotransferase, creatine phosphokinase, and elevated cortisol levels in MNR concomitant with decreased blood insulin in male fetal MNR were measured. MNR resulted in a two-fold increase in fetal LV mtDNA. NMR resulted in increased transcripts for several respiratory chain (NDUFB8, UQCRC1, and cytochrome c) and ATP synthase proteins However, MNR fetal LV mitochondrial complex I and complex II/III activities were significantly decreased, possibly contributing to the 73% decreased ATP content and increased lipid peroxidation. MNR fetal LV showed mitochondria with sparse and disarranged cristae dysmorphology. Conclusions: MNR disruption of fetal cardiac mitochondrial fitness likely contributes to the documented developmental programming of adult cardiac dysfunction, indicating a programmed mitochondrial inability to deliver sufficient energy to cardiac tissues as a chronic mechanism for later-life heart failure.

scholarly journals Viral Loads Within 6 Weeks After Diagnosis of HIV Infection in Early and Later Stages: Observational Study Using National Surveillance Data (Preprint)

2018 ◽  
Author(s):  
Richard M. Selik ◽  
Laurie Linley
Keyword(s):  
Viral Load ◽  
Hiv Infection ◽  
Acute Infection ◽  
Antibody Test ◽  
Case Definition ◽  
Positive Test ◽  
Median Viral Load ◽  
Acute Hiv Infection ◽  
Viral Loads ◽  
Hiv 1

BACKGROUND Early (including acute) HIV infection is associated with viral loads higher than those in later stages. OBJECTIVE This study aimed to examine the association between acute infection and viral loads near the time of diagnosis using data reported to the US National HIV Surveillance System. METHODS We analyzed data on infections diagnosed in 2012-2016 and reported through December 2017. Diagnosis and staging were based on the 2014 US surveillance case definition for HIV infection. We divided early HIV-1 infection (stage 0) into two subcategories. Subcategory 0α: a negative or indeterminate HIV-1 antibody test was ≤60 days after the first confirmed positive HIV-1 test or a negative or indeterminate antibody test or qualitative HIV-1 nucleic acid test (NAT) was ≤180 days before the first positive test, the latter being a NAT or detectable viral load. Subcategory 0β: a negative or indeterminate antibody or qualitative NAT was ≤180 days before the first positive test, the latter being an HIV antibody or antigen/antibody test. We compared median earliest viral loads for each stage and subcategory in each of the first 6 weeks after diagnosis using only the earliest viral load for each individual. RESULTS Of 203,392 infections, 56.69% (115,297/203,392) were reported with a quantified earliest viral load within 6 weeks after diagnosis and criteria sufficient to determine the stage at diagnosis. Among 5081 infections at stage 0, the median earliest viral load fell from 694,000 copies/mL in week 1 to 125,022 in week 2 and 43,473 by week 6. Among 30,910 infections in stage 1, the median earliest viral load ranged 15,412-17,495. Among 42,784 infections in stage 2, the median viral load declined from 44,973 in week 1 to 38,497 in week 6. Among 36,522 infections in stage 3 (AIDS), the median viral load dropped from 205,862 in week 1 to 119,000 in week 6. The median earliest viral load in stage 0 subcategory 0α fell from 1,344,590 copies/mL in week 1 to 362,467 in week 2 and 47,320 in week 6, while that in subcategory 0β was 70,114 copies/mL in week 1 and then 32,033 to 44,067 in weeks 2-6. The median viral load in subcategory 0α was higher than that in subcategory 0β in each of the first 6 weeks after diagnosis (P<.001). CONCLUSIONS In the 1st week after diagnosis, viral loads in early infections are generally several times higher than those in later stages at diagnosis. By the 3rd week, however, most are lower than those in stage 3. High viral loads in early infection are much more common in subcategory 0α than in subcategory 0β, consistent with 0α comprising mostly acute infections and 0β comprising mostly postacute early infections. These findings may inform the prioritization of interventions for prevention.

scholarly journals Different Patterns of HIV-1 Replication in MACROPHAGES is Led by Co-Receptor Usage

Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 297 ◽  
Author(s):  
Borrajo ◽  
Ranazzi ◽  
Pollicita ◽  
Bellocchi ◽  
Salpini ◽  
...  
Keyword(s):  
Cell Death ◽  
Chemokine Receptor ◽  
Post Infection ◽  
Fold Increase ◽  
Initial Increase ◽  
Limited Information ◽  
Induce Cell Death ◽  
Receptor Usage ◽  
The Impact ◽  
Hiv 1

Background and objectives: To enter the target cell, HIV-1 binds not only CD4 but also a co-receptor β-chemokine receptor 5 (CCR5) or α chemokine receptor 4 (CXCR4). Limited information is available on the impact of co-receptor usage on HIV-1 replication in monocyte-derived macrophages (MDM) and on the homeostasis of this important cellular reservoir. Materials and Methods: Replication (measured by p24 production) of the CCR5-tropic 81A strain increased up to 10 days post-infection and then reached a plateau. Conversely, the replication of the CXCR4-tropic NL4.3 strain (after an initial increase up to day 7) underwent a drastic decrease becoming almost undetectable after 10 days post-infection. The ability of CCR5-tropic and CXCR4-tropic strains to induce cell death in MDM was then evaluated. While for CCR5-tropic 81A the rate of apoptosis in MDM was comparable to uninfected MDM, the infection of CXCR4-tropic NL4.3 in MDM was associated with a rate of 14.3% of apoptotic cells at day 6 reaching a peak of 43.5% at day 10 post-infection. Results: This suggests that the decrease in CXCR4-tropic strain replication in MDM can be due to their ability to induce cell death in MDM. The increase in apoptosis was paralleled with a 2-fold increase in the phosphorylated form of p38 compared to WT. Furthermore, microarray analysis showed modulation of proapoptotic and cancer-related genes induced by CXCR4-tropic strains starting from 24 h after infection, whereas CCR5 viruses modulated the expression of genes not correlated with apoptotic-pathways. Conclusions: In conclusion, CXCR4-tropic strains can induce a remarkable depletion of MDM. Conversely, MDM can represent an important cellular reservoir for CCR5-tropic strains supporting the role of CCR5-usage in HIV-1 pathogenesis and as a pharmacological target to contribute to an HIV-1 cure.

Can I go back to work? A case of persistent SARS-CoV-2 with advanced untreated HIV infection

2021 ◽  
pp. 095646242110516
Author(s):  
Rhys D Wenlock ◽  
Colin S Brown ◽  
Collins Iwuji ◽  
Jaime H Vera
Keyword(s):  
Hiv Infection ◽  
Return To Work ◽  
Post Infection ◽  
Care Home ◽  
Transmission Risk ◽  
Hiv 1 ◽  
Back To Work

We describe the case of a 30-year-old care home employee diagnosed with COVID-19 and acute untreated HIV-1. He was unable to return to work for 119 days due to concerns over transmission risk as his SARS-CoV-2 PCR remained detectable. This highlights the uncertainty in interpreting SARS-CoV-2 PCR results post-infection in acute untreated HIV.

scholarly journals Longitudinal imaging of HIV-1 spread in humanized mice with parallel 3D immunofluorescence and electron tomography

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Collin Kieffer ◽  
Mark S Ladinsky ◽  
Allen Ninh ◽  
Rachel P Galimidi ◽  
Pamela J Bjorkman
Keyword(s):  
Post Infection ◽  
Electron Tomography ◽  
Virus Production ◽  
Humanized Mice ◽  
Lymphoid Tissues ◽  
Human Patient ◽  
Viral Loads ◽  
Infected Cells ◽  
Longitudinal Imaging ◽  
Hiv 1

Dissemination of HIV-1 throughout lymphoid tissues leads to systemic virus spread following infection. We combined tissue clearing, 3D-immunofluorescence, and electron tomography (ET) to longitudinally assess early HIV-1 spread in lymphoid tissues in humanized mice. Immunofluorescence revealed peak infection density in gut at 10–12 days post-infection when blood viral loads were low. Human CD4+ T-cells and HIV-1–infected cells localized predominantly to crypts and the lower third of intestinal villi. Free virions and infected cells were not readily detectable by ET at 5-days post-infection, whereas HIV-1–infected cells surrounded by pools of free virions were present in ~10% of intestinal crypts by 10–12 days. ET of spleen revealed thousands of virions released by individual cells and discreet cytoplasmic densities near sites of prolific virus production. These studies highlight the importance of multiscale imaging of HIV-1–infected tissues and are adaptable to other animal models and human patient samples.

scholarly journals The Effects of Syphilis Infection on CD4 Counts and HIV-1 RNA Viral Loads in Blood: A Cohort Study Among MSM with HIV Infection in Sanglah Hospital Bali-Indonesia

2016 ◽  
Vol 5 (3) ◽  
pp. 33 ◽  
Author(s):  
I Ketut Agus Somia ◽  
Ketut Tuti Parwati Merati ◽  
Dewi Dian Sukmawati ◽  
Nittaya Phanuphak ◽  
IGAA Elis Indira ◽  
...  
Keyword(s):  
Cohort Study ◽  
Hiv Infection ◽  
Syphilis Infection ◽  
Cd4 Counts ◽  
Viral Loads ◽  
Hiv 1

Localization of endothelial nitric oxide synthase in the normal and failing human atrial myocardium

1996 ◽  
Vol 54 ◽  
pp. 786-787
Author(s):  
Chi-Ming Wei ◽  
Margarita Bracamonte ◽  
Shi-Wen Jiang ◽  
Richard C. Daly ◽  
Christopher G.A. McGregor ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Cardiac Tissues ◽  
Mammalian Tissues ◽  
End Stage Heart Failure ◽  
End Stage ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Nitric oxide (NO) is a potent endothelium-derived relaxing factor which also may modulate cardiomyocyte inotropism and growth via increasing cGMP. While endothelial nitric oxide synthase (eNOS) isoforms have been detected in non-human mammalian tissues, expression and localization of eNOS in the normal and failing human myocardium are poorly defined. Therefore, the present study was designed to investigate eNOS in human cardiac tissues in the presence and absence of congestive heart failure (CHF).Normal and failing atrial tissue were obtained from six cardiac donors and six end-stage heart failure patients undergoing primary cardiac transplantation. ENOS protein expression and localization was investigated utilizing Western blot analysis and immunohistochemical staining with the polyclonal rabbit antibody to eNOS (Transduction Laboratories, Lexington, Kentucky).

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