Although highly active antiretroviral therapy (HAART) has positively altered the morality rates in HIV-infected children, these drugs have the potential to cause significant morbidity. These drugs ...cause changes in fat distribution, lipid profiles, glucose, homeostasis, and bone turnover. The direct relationship between duration of drug exposure and increased risk of cardiovascular disease is particularly concerning for HIV-infected infants and children, who likely will have longer cumulative exposure to HAART. It is unclear whether the metabolic effects of decades of exposure would be reversible with cessation of therapy. The benefits of HAART in HIV infection are indisputable, but the impetus to find a cure or design more tolerable therapy is clear. Infarction may replace infection as the major cause of morbidity and mortality from HIV.
Cardiovascular Disease, Statins, and HIV Eckard, Allison Ross; Meissner, Eric G.; Singh, Inderjit ...
The Journal of infectious diseases,
10/2016, Letnik:
214, Številka:
suppl 2
Journal Article
Recenzirano
Odprti dostop
Human immunodeficiency virus (HIV)-infected patients are at an increased risk of serious, non-AIDS-defining comorbidities, even in the setting of viral suppression with combination antiretroviral ...therapy. This increased risk is due in part to immune dysfunction and heightened inflammation and immune activation associated with chronic HIV infection. Statins have wide-reaching immunomodulatory effects, and their use in the HIV-infected population may be of particular benefit. In this article, we review the pathogenesis of increased inflammation during HIV infection and how it contributes to the risk of cardiovascular disease among HIV-infected individuals. We then we review the immunomodulatory effects of statins and how they may attenuate the risk of cardiovascular disease and other comorbidities in this unique patient population.
The aim of this study was to assess the effect of antiretroviral therapy (ART) versus HIV on mitochondria in fat.
Subcutaneous fat was collected from 45 HIV-infected patients on ART with lipoatrophy, ...11 HIV-infected ART-naive patients and nine healthy controls. Three mitochondrial transcripts: NADH dehydrogenase subunit 1 (ND1), cytochrome B (CYTB) and NADH dehydrogenase subunit 6 (ND6) genes were quantitated using TaqMan probes and normalized to nuclear-encoded ribosomal L13.
ND1/L13 and CYTB/L13 were lower in HIV-positive patients on ART with lipoatrophy versus ART-naive patients (3.4 versus 7.2 P=0.017 and 2.5 versus 4.6 P=0.006, respectively). No difference was found between ART-naive patients and controls (P>0.70). ND6/L13 was similar between all groups. Dual-energy X-ray absorptiometry-measured limb fat and mitochondrial DNA in fat were also lower in HIV-positive patients on ART with lipoatrophy versus HIV-infected, ART-naive patients (4,382 versus 7,662 g P=0.02 and 726 versus 1,372 copies/cell P=0.03, respectively), but no difference was found between ART-naive and controls. In a multiple regression analysis, limb fat correlated with all three mitochrondrial RNA, whereas mitochondrial DNA did not correlate with mitochondrial RNA or limb fat.
In contrast to ART-naive patients, HIV-positive patients on ART with lipoatrophy had significant depletion in mitochondrial DNA in fat and mitochondrial RNAs. This suggests that mitochondrial toxicity in lipoatrophy could be driven by ART and not by HIV itself. In addition, mitochondrial RNA abnormalities, and not mitochondrial DNA depletion, could be a key driving force behind lipoatrophy.
(1) Vitamin D deficiency is associated with mortality in the general population and has been observed in one rheumatoid arthritis (RA) cohort. Here, we investigate the relationship between ...25-hydroxyvitamin D (25(OH)D) levels before methotrexate (MTX) therapy initiation in patients with RA and the subsequent all-cause mortality in a national Veterans Affairs (VA) cohort. (2) This is a retrospective study on RA patients time-oriented around the initial MTX prescription and 25(OH)D levels before starting MTX. We examined survival in patients with 25(OH)D levels > 50 nmol/L and ≤50 nmol/L using the Cox Proportional Hazard Model and fully adjusted for risk factors. (3) In total, 15,109 RA patients were included in the nationwide cohort. RA patients with 25(OH)D levels > 50 nmol/L before starting MTX had a 28% reduced risk of mortality when compared to those with levels ≤ 50 nmol/L (HR: 0.72, CI: 0.64-0.80,
< 0.001) after adjusting for traditional risk factors. (4) In this national RA cohort receiving standard-of-care MTX, patients with 25(OH)D levels > 50 nmol/L have a lower subsequent mortality when compared to those with 25(OH)D levels ≤ 50 nmol/L. It remains to be determined whether increasing Vitamin D levels in RA patients initially found to be Vitamin D deficient impacts their all-cause mortality.
Objectives
The aim of the study was to determine the effect of alendronate (
ALN
) on inflammatory markers and osteoprotegerin (
OPG
)/receptor activator of nuclear factor‐kappa
B
ligand (
RANKL
), ...and to explore the associations of baseline systemic inflammation and vitamin
D
status on the bone mineral density (
BMD
) response to
ALN
.
Methods
Eighty‐two
HIV
‐positive patients with lumbar spine
T
‐score ≤ −1.5 were randomized to
ALN
70 mg weekly or placebo for 48 weeks; all received calcium carbonate 500 mg/vitamin
D
3 200
IU
twice daily. Serum
C
‐telopeptide (
CTx
) and
BMD
were assessed at baseline and week 48. Stored plasma samples in 70 subjects were assayed for levels of 25‐hydroxyvitamin
D
(25(
OH
)
D
),
OPG
,
RANKL
, interleukin (
IL
)‐6 and soluble receptors for tumour necrosis factor (
TNF
)‐α 1 and 2 (
sTNFR
1 and 2).
Results
ALN
increased
BMD
more than placebo at both the lumbar spine (difference
ALN
− placebo 2.64%;
P
= 0.011) and the total hip (difference 2.27%;
P
= 0.016). No within‐ or between‐arm differences in
OPG
,
RANKL
or inflammatory markers were observed over 48 weeks. High baseline
CTx
and
sTNFR2
were associated with a more robust
BMD
response to
ALN
over 48 weeks at the lumbar spine difference 5.66%; 95% confidence interval (
CI
) 3.50, 7.82;
P
< 0.0001 and total hip (difference 4.99%; 95%
CI
2.40, 7.57;
P
= 0.0002), respectively. Baseline 25(
OH
)
D
< 32 ng/mL was associated with larger increases in total hip
BMD
over 48 weeks, independent of
ALN
treatment (
P
= 0.014).
Conclusions
Among
HIV
‐positive patients, higher baseline bone resorption and
TNF
‐α activity were associated with an increased
BMD
response to
ALN
. The greater
BMD
response in those with lower vitamin
D
reinforces the importance of vitamin
D
supplementation with bisphosphonate treatment.
Anisocytosis or increased red blood cell distribution width (RDW) has been associated with an elevated cardiovascular risk, especially in patients with coronary artery disease and heart failure.1,2 ...Anisocytosis has been linked with markers of systemic inflammation, oxidative stress, and iron metabolism.3 However, the mechanism linking RDW with cardiovascular outcomes remains unknown. A second model demonstrated RDW remained negatively correlated (rho = −0.32, p = 0.044) with mean bone marrow SUV despite accounting Model 1 with the addition of biomarkers of inflammation (IL6, high sensitivity C-reactive protein). The limitations of our study include the small sample size, single RDW measurement, no direct analysis of bone marrow function, and possible other confounders (including significant portion of males and heroin users).
Abstract Background HIV-infection is characterized by chronic immune activation that persists despite effective antiretroviral therapy (ART) and is associated with elevated cardiovascular risk. ...Whether specific perivascular fat depots are associated with inflammation in HIV is unknown. Methods In a cross-sectional study, epicardial (EAT) and thoracic periaortic (TAT) adipose tissue volumes were measured by computed tomography in 100 HIV-infected adults, on stable ART, with LDL-cholesterol ≤ 130 mg/dL and evidence of heightened T-cell activation (CD8+CD38+HLA-DR+ ≥ 19%) or increased inflammation (high sensitivity C-reactive protein ≥ 2 mg/L). Results Overall, 77% were males and 70% African American. Mean (standard deviation) age and body mass index were 47 (10) years and 28 (6.4) kg/m2 , respectively. All subjects had HIV-1 RNA < 1000 copies/mL with mean (standard deviation) CD4 + T cell count of 665 (280) cells/μL; 50% were on a protease inhibitor. EAT and TAT were correlated with each other (r = 0.766, p < 0.0001). Both were associated with metabolic syndrome, atherogenic lipid profile, insulin resistance, total and central body fat, serum biomarkers of inflammation, and soluble CD163, but not with cellular immune activation markers. In multivariable models that adjusted for age, sex, and other measures of adiposity, both perivascular fat depots were independently associated with the presence of coronary calcium. Conclusions Perivascular fat is associated with soluble CD163, biomarkers of inflammation, insulin resistance, and subclinical atherosclerosis in this population of virologically suppressed HIV-infected patients on ART. The association of perivascular fat with coronary artery calcification appears to be independent of other measures of adiposity.
Since the advent of potent antiretroviral therapy in combination regimens, multiple epidemiologic studies have shown that osteopenia and osteoporosis are common among patients with HIV infection. ...However, there remain many areas of uncertainty about this potential complication, which can be confusing for the HIV clinician. This review summarizes the epidemiology, pathophysiology, suggested screening strategies, and management options of decreased bone mineral density in patients with HIV. Our aims are to review the available data, highlight controversial issues, and provide guidance for clinicians where supporting data are unavailable.
PDF
