Abstract
Background
Few data exist on cardiac fibrosis and inflammation in youth with HIV, particularly in sub-Saharan Africa.
Purpose
Our objective was to assess the association between HIV status ...and cardiovascular magnetic resonance (CMR) measures of subclinical cardiac fibrosis, inflammation, and function.
Methods
We performed CMR on a cross-section of youth in South Africa: youth with perinatally acquired HIV (YPHIV), youth with non-perinatally acquired HIV (YNPHIV), and HIV-seronegative youth (YHIV-). Subclinical fibrosis late gadolinium enhancement (LGE) mass and fraction, extracellular volume (ECV), inflammation native T1 and T2 mapping, and cardiac function (cine, strain, and strain rate) were assessed. CD4, viral load (VL), and fasting glucose, insulin for Homeostatic Model Assessment-Insulin Resistance (HOMA) and lipids were obtained. Unadjusted and adjusted quantile regression models were used to assess the association between HIV status and CMR outcomes. In sub-group analyses of youth with HIV, we additionally adjusted for HIV factors.
Results
Of 464 youth, 287 were YPHIV, 87 YNPHIV, and 90 YHIV-. YNPHIV were older with a higher proportion self-identifying as female than YPHIV and YHIV- (median age 20 vs 18 and 17 years; 85% vs 50% and 49%, respectively). YPHIV had lower body surface area (1.6 vs 1.7 and 1.7m2) and a higher proportion with prior TB disease (70% vs. 20% vs 8%) compared to YNPHIV and YHIV-. Tobacco use, HOMA, total cholesterol, and low-density lipoproteins were similar between groups. Among youth with HIV, YPHIV had a higher proportion with CD4<200 cells/mm3 (10% vs 4%) or VL>50 copies/mL (39% vs 13%) but lower proportion on integrase inhibitors (33% vs 84%). LGE mass (0.13 vs 0.12 vs 0.07g respectively) and fraction (0.3% vs 0.3% vs. 0.2% respectively) were higher in YPHIV and YNPHIV than YHIV-; native T1 was highest in YNPHIV compared to YPHIV and YHIV- (Table). In adjusted analyses, compared to YHIV-, median LGE mass was higher in YPHIV and YNPHIV (β:0.06, p=0.01 for YPHIV, β:0.05, p=0.03 for YNPHIV) and LGE% was higher in YPHIV (β:0.14, p=0.02); native T1 and ECV did not differ between groups in adjusted analyses. Among youth with HIV, CMR outcomes did not differ significantly for persons with perinatal vs non-perinatal HIV. Findings did not vary in analyses restricted to females.
Conclusion
In one of the largest studies of CMR among youth with HIV in sub-Saharan Africa, we found that despite their young age, YPHIV and YNPHIV appear to have higher subclinical cardiac fibrosis than YHIV- and healthy adults in South Africa. Youth with HIV may benefit from early screening and long-term monitoring for cardiovascular disease.TableFigure
To assess carotid intima media thickness (IMT) and cardiac biomarkers in HIV infected children on antiretroviral therapy (ART).
This was a single site, cross sectional, controlled observational ...study. We assessed carotid IMT, homocysteine, high-sensitivity C-reactive protein and myeloperoxidase levels in HIV infected children on stable ART for >or= 6 months. Carotid IMT was reported as internal carotid artery (ICA) and common carotid artery (CCA) thickness; left and right sides were measured separately. Groups were compared using appropriate two-sample tests.
Of the 62 subjects enrolled, 31 were HIV positive (50%), 66% were female, and 69% were African-American. Median CD4% was 32% and 26 patients (84%) had HIV-1 RNA< 400 copies/ml. Sixteen patients had been taking protease inhibitors for a median duration of 27 months. None had hypertension or smoked. HIV infected children had higher HOMA-IR, waist-to-hip ratio, cholesterol, triglycerides, myeloperoxidase and lower homocysteine levels. Left and right CCA IMT, and left and right ICA IMT were significantly higher in the HIV infected group. Significant predictors of carotid IMT measurements in uninfected controls were body mass index and homocysteine, but only the duration of ARV therapy was predictive of IMT in the HIV infected group.
Higher levels of carotid IMT and some cardiac markers were found in ART treated HIV infected children when compared to matched uninfected controls. These results suggest that HIV infected children receiving ART may be at increased risk of cardiovascular disease.
Mitochondrial DNA (mtDNA) influences metabolic diseases and perhaps antiretroviral therapy (ART) complications. We explored associations between European mtDNA haplogroups and metabolic changes among ...A5142 participants.
Seven hundred and fifty-seven ART-naive patients were randomized to one of three class-sparing ART regimens including efavirenz and/or lopinavir/ritonavir with or without nucleoside reverse transcriptase inhibitors (NRTIs). Nonrandomized NRTIs included stavudine, tenofovir, or zidovudine, each with lamivudine. Fasting lipid profiles and whole-body dual-energy X-ray absorptiometry (DEXA) were performed. Nine European mtDNA haplogroups were determined for 231 self-identified non-Hispanic white individuals. Metabolic changes from baseline to 96 weeks were analyzed by haplogroup.
Median age was 39 years, 9% were women, and 37, 32, and 30 were randomized to NRTI-containing regimens with either efavirenz or lopinavir/ritonavir, and an NRTI-sparing regimen, respectively. Among NRTI-containing regimens, 51% included zidovudine, 28% tenofovir, and 21% stavudine. Compared with other haplogroups, mtDNA haplogroup I (N = 10) had higher baseline non-HDL cholesterol 160 mg/dl (interquartile range 137-171) vs. 120 mg/dl (104-136); P = 0.005, a decrease in non-HDL cholesterol over 96 weeks -14% (-20 to 6) vs. +25% (8 to 51); P < 0.001, tended to have more baseline extremity fat, and had more extremity fat loss by DEXA -13% (-13 to 12) vs. +9% (-13 to 26); P = 0.08 and lipoatrophy (50 vs. 20%; P = 0.04). Haplogroup W (N = 5; all randomized to NRTI-sparing regimens) had the greatest increase in extremity fat +35.5% (26.8 to 54.9); P = 0.02.
Lipids and extremity fat were associated with European mtDNA haplogroups in this HIV-infected population. These preliminary results suggest that mitochondrial genomics may influence metabolic parameters before and during ART.
To assess the association of inflammatory and endothelial activation biomarkers with the presence of lipoatrophy in HIV-infected subjects and to examine the role of HIV, antiretroviral therapy (ART), ...and metabolic parameters in endothelial activation and inflammation.
Prospective, cross-sectional study including 4 groups: HIV+ on ART with HIV-1 RNA<1000 copies/mL with and without clinical lipoatrophy, HIV+ ART naive, and healthy controls.
We measured plasma levels of inflammatory cytokines (tumor necrosis factor-alpha, soluble tumor necrosis factor receptors I and II, interleukin-6, C-reactive protein, and myeloperoxidase) and endothelial activation markers (soluble intercellular and vascular cell adhesion molecules and von Willebrand factor).
We enrolled 182 subjects. Limb fat and lipoatrophy status were not correlated with endothelial markers. Endothelial markers were higher in HIV+ ART naive when compared with healthy controls and with HIV+ on ART but were similar between HIV+ on ART and healthy controls. Neither endothelial nor inflammatory markers were correlated with HIV duration, CD4 count, lipids, glucose, or specific ART. Strong correlations were found between some inflammatory cytokines and endothelial markers.
There is enhanced endothelial activation in ART naive, whereas HIV+ on ART has similar values to healthy controls. Lipoatrophy did not seem to affect endothelial activation. Results highlight a potential association between heightened inflammation and endothelial activation.
Stavudine use is a contributing factor for lipoatrophy, whereas use of abacavir or zidovudine is less likely to cause this complication. The TARHEEL study was a 48-week, open-label study that ...assessed changes in lipoatrophy after abacavir (86 patients 73%) or zidovudine (32 patients 27%), 300 mg twice daily, was substituted for stavudine for 118 human immunodeficiency virus (HIV)–infected patients (HIV type 1 RNA level, <400 copies/mL) with virological suppression who had developed lipoatrophy after ⩾6 months of stavudine-based treatment. At week 48, full-body dual-energy x-ray absorptiometry demonstrated a median increase in arm fat of 35%, leg fat of 12%, and trunk fat of 18%, compared with the baseline level. These improvements coincided with fat gain in lipoatrophic areas that was documented by computerized tomography. Results of a “body image” questionnaire showed that a substantial percentage of patients reported some or a lot of fat gain in the arms (22%), legs (18%), buttocks (19%), and face (27%). HIV suppression was maintained over the study period. In conclusion, replacing stavudine with abacavir or zidovudine resulted in improvement in stavudine-induced lipoatrophy.
Survivalin HIV-infected children has greatly improved with the introduction of highly active antiretroviral therapy. Children are more vulnerable than adults to metabolic side effects of therapy ...because of its potential impact on growth and the children’s likely greater cumulative exposure. This review summarizes the epidemiology and management of lipodystrophy, dyslipidemia, insulin resistance, hyperlactatemia, osteopenia and growth failure in HIV-infected children.
OBJECTIVES:Some studies suggest that bioavailable 25-(OH)D is more accurate than total 25-(OH)D as an assessment of vitamin D status in black individuals, We hypothesized that increases in ...bioavailable 25-(OH)D would correlate better with improvement in bone outcomes among black HIV-infected adults.
DESIGN:This is a secondary analysis of ACTG A5280, a randomized, double-blind study of Vitamin D3 and calcium (VitD/Ca) supplementation in HIV-infected participants initiating antiretroviral therapy (ART).
METHODS:Effect of VitD/Ca on total and calculated bioavailable 25-(OH)D, parathyroid hormone (PTH), bone turnover markers (BTMs) and bone mineral density (BMD) in black and non-black participants were evaluated at 48 weeks. Wilcoxon signed-rank tests and Wilcoxon rank sum tests assessed within and between-race differences.
RESULTS:Of 165 participants enrolled, 129 (40 black and 89 non-black) had complete data. At baseline, black participants had lower total 25-(OH)D median (Q1,Q3) 22.6 (15.8, 26.9) vs. 31.1 (23.1, 38.8) ng/ml, p < 0.001 but higher bioavailable 25-(OH)D 2.9 (1.5, 5.2) vs. 2.0 (1.5, 3.0) ng/ml, p=0.022 than non-black participants. After 48 weeks of VitD/Ca supplementation, bioavailable 25-(OH)D increased more in black than non-black participants, but there were no between-race differences in change in BTMs or BMD. The associations between increases in 25-(OH)D levels and change in bone outcomes appeared similar for both total and bioavailable 25-(OH)D.
CONCLUSIONS:Baseline and change in bioavailable 25-(OH)D were higher among black adults initiating ART with VitD/Ca; however, associations between 25-(OH)D and bone outcomes appeared similar for total and bioavailable 25-(OH)D. The assessment of total 25-(OH)D may be sufficient for evaluation of vitamin D status in black HIV-infected individuals.
Background
D-Dimer elevations have been associated with a striking increase in mortality in HIV-infected patients. However, D-Dimer has not been directly linked to endothelial dysfunction in HIV.
...Methods
In this cross-sectional study, we used flow-mediated dilation (FMD) of the brachial artery to measure endothelial function and several biomarkers to measure systemic inflammation and coagulation activation in HIV-infected adults on stable antiretroviral therapy with HIV-1 RNA levels <400 copies/ml. Multivariable linear regression was used to model FMD by these markers, traditional cardiovascular risk factors and HIV-related characteristics.
Results
Analysis included 98 subjects (88% male, median age 47.5 years, CD4+ T-cells 578.5 cells/mm3); all on ART (52% on protease inhibitors). The only factors independently associated with FMD were D-Dimer and body mass index.
Conclusions
We show for the first time an independent association between D-Dimer and endothelial dysfunction in virologically suppressed, HIV-infected adults on stable antiretroviral therapy, potentially explaining the link between D-Dimer and mortality in HIV.
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