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1.
J Endocr Soc ; 8(8): bvae120, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38974987

ABSTRACT

Context: Cardiovascular disease (CVD) in transgender women (TW) may be affected by gender-affirming hormone therapy (GAHT) and HIV, but few data compare TW on contemporary GAHT to well-matched controls. Objective: We compared CVD burden and biomarker profiles between TW and matched cisgender men (CM). Methods: Adult TW on GAHT (n = 29) were recruited for a cross-sectional study (2018-2020). CM (n = 48) from the former Multicenter AIDS Cohort Study were matched 2:1 to TW on HIV serostatus, age ±5 years, race/ethnicity, BMI category and antiretroviral therapy (ART) type. Cardiac parameters were measured by CT and coronary atherosclerosis by coronary CT angiography; sex hormone and biomarker concentrations were measured centrally from stored samples. Results: Overall, median age was 53 years and BMI 29 kg/m2; 69% were non-white. All participants with HIV (71%) had viral suppression on ART. Only 31% of TW had testosterone suppression (<50 ng/dL, TW-S). Traditional CVD risk factors were similar between groups, except that TW-S had higher BMI than TW with non-suppressed testosterone (TW-T). TW-S had no evidence of non-calcified coronary plaque or advanced coronary stenosis, whereas TW-T and CM had similar burden. TW had lower prevalence of any coronary plaque, calcified plaque and mixed plaque than CM, regardless of testosterone concentrations and HIV serostatus. Estradiol but not testosterone concentrations moderately and negatively correlated with the presence of coronary plaque and stenosis. Small sample size limited statistical power. Conclusion: Older TW with suppressed total testosterone on GAHT had no CT evidence of non-calcified coronary plaque or advanced coronary stenosis. Longitudinal studies to understand relationships between GAHT and CVD risk in TW are needed.

2.
AIDS ; 38(10): 1485-1493, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38788204

ABSTRACT

BACKGROUND: People with HIV (PWH) are at greater risk for diastolic dysfunction compared with persons without HIV (PWOH). An increase in visceral adipose tissue is common among PWH and greater visceral adipose tissue is associated with diastolic dysfunction among PWOH. We investigated associations of visceral adipose tissue, subcutaneous adipose tissue, and other fat depots with subclinical diastolic dysfunction among men with and without HIV (MWH and MWOH). DESIGN: Cross-sectional analysis of MWH and MWOH in the Multicenter AIDS Cohort Study (MACS). METHODS: Participants underwent echocardiography for diastolic dysfunction assessment and CT scanning including subcutaneous, visceral, epicardial, and liver adiposity measurements. Diastolic dysfunction was defined by characterizing heart function on antiretroviral therapy0 criteria. Odds for diastolic dysfunction with each measure of adiposity were estimated using multivariable logistic regression. RESULTS: Among 403 participants (median age 57, 55% white, median BMI 26 kg/m 2 ), 25% met criteria for diastolic dysfunction and 59% MWH (82% undetectable plasma HIV RNA). Greater epicardial adipose tissue area was associated with higher odds of diastolic dysfunction [odds ratio:1.54 per SD; 95%confidence interval (CI) 1.15-2.05] when adjusted for demographics, HIV serostatus, and cardiovascular risk factors. This association did not differ by HIV serostatus and persisted when excluding MWH who were not virally suppressed. Less subcutaneous adipose tissue was associated with higher odds of diastolic dysfunction. Other adipose depots were not associated with diastolic dysfunction. CONCLUSION: Greater epicardial adipose tissue and less subcutaneous adipose tissue were associated with diastolic dysfunction, regardless of HIV serostatus and viral suppression. Greater epicardial adipose tissue and less subcutaneous adipose tissue observed among PWH may contribute to risk for heart failure with preserved ejection fraction in this population.


Subject(s)
HIV Infections , Intra-Abdominal Fat , Subcutaneous Fat , Humans , Male , HIV Infections/complications , HIV Infections/drug therapy , Cross-Sectional Studies , Middle Aged , Subcutaneous Fat/diagnostic imaging , Intra-Abdominal Fat/diagnostic imaging , Pericardium/diagnostic imaging , Echocardiography , Adult , Tomography, X-Ray Computed , Aged
3.
Nat Commun ; 15(1): 3035, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38600088

ABSTRACT

People living with HIV (PLWH) experience increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors associated with this vulnerability remain uncertain. In the general population, alterations in the N-glycans on IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG N-glycans in cross-sectional and longitudinal samples from 1214 women and men, living with and without HIV. PLWH exhibit an accelerated accumulation of pro-aging-associated glycan alterations and heightened expression of senescence-associated glycan-degrading enzymes compared to controls. These alterations correlate with elevated markers of inflammation and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit a reduced ability to elicit anti-HIV Fc-mediated immune activities. These findings hold potential for the development of biomarkers and tools to identify and prevent premature aging and comorbidities in PLWH.


Subject(s)
Aging, Premature , HIV Infections , Male , Humans , Female , Immunoglobulin G , Cross-Sectional Studies , Aging , Inflammation/complications , Polysaccharides
4.
Stroke ; 55(3): 651-659, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38333992

ABSTRACT

BACKGROUND: HIV and hepatitis C virus (HCV) are associated with increased risk of carotid artery atherosclerotic plaque and stroke. We examined associations of HIV- and HCV-related factors with echomorphologic features of carotid artery plaque. METHODS: This cross-sectional study included participants from the MACS (Multicenter AIDS Cohort Study)/WIHS (Women's Interagency HIV Study) Combined Cohort Study who underwent high-resolution B-mode carotid artery ultrasound. Plaques were characterized from 6 areas of the right carotid artery. Poisson regression controlling for demographic and cardiometabolic risk factors determined adjusted prevalence ratios (aPRs) and 95% CIs for associations of HIV- and HCV-related factors with echomorphologic features. RESULTS: Of 2655 participants (65% women, median age 44 [interquartile range, 37-50] years), 1845 (70%) were living with HIV, 600 (23%) were living with HCV, and 425 (16%) had carotid plaque. There were 191 plaques identified in 129 (11%) women with HIV, 51 plaques in 32 (7%) women without HIV, 248 plaques in 171 (28%) men with HIV, and 139 plaques in 93 (29%) men without HIV. Adjusted analyses showed that people with HIV and current CD4+ count <200 cells/µL had a significantly higher prevalence of predominantly echolucent plaque (aPR, 1.86 [95% CI, 1.08-3.21]) than those without HIV. HCV infection alone (aPR, 1.86 [95% CI, 1.08-3.19]) and HIV-HCV coinfection (aPR, 1.75 [95% CI, 1.10-2.78]) were each associated with higher prevalence of predominantly echogenic plaque. HIV-HCV coinfection was also associated with higher prevalence of smooth surface plaque (aPR, 2.75 [95% CI, 1.03-7.32]) compared with people without HIV and HCV. CONCLUSIONS: HIV with poor immunologic control, as well as HCV infection, either alone or in the presence of HIV, were associated with different echomorphologic phenotypes of carotid artery plaque.


Subject(s)
Carotid Artery Diseases , Carotid Stenosis , Coinfection , HIV Infections , Hepatitis C , Plaque, Atherosclerotic , Adult , Female , Humans , Male , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/epidemiology , Carotid Artery Diseases/complications , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/epidemiology , Carotid Stenosis/complications , Cohort Studies , Coinfection/diagnostic imaging , Coinfection/epidemiology , Coinfection/complications , Cross-Sectional Studies , Hepacivirus , Hepatitis C/complications , Hepatitis C/diagnostic imaging , Hepatitis C/epidemiology , HIV Infections/complications , HIV Infections/diagnostic imaging , HIV Infections/epidemiology , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/epidemiology , Plaque, Atherosclerotic/complications , Risk Factors , Middle Aged , Multicenter Studies as Topic
5.
AIDS ; 38(4): 465-475, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-37861689

ABSTRACT

OBJECTIVE: The aim of this study was to determine whether urine biomarkers of kidney health are associated with subclinical cardiovascular disease among men with and without HIV. DESIGN: A cross-sectional study within the Multicenter AIDS Cohort Study (MACS) among 504 men with and without HIV infection who underwent cardiac computed tomography scans and had urine biomarkers measured within the preceding 2 years. METHODS: Our primary predictors were four urine biomarkers of endothelial (albuminuria), proximal tubule dysfunction (alpha-1-microglobulin [A1 M] and injury (kidney injury molecule-1 [KIM-1]) and tubulointerstitial fibrosis (pro-collagen-III N-terminal peptide [PIIINP]). These were evaluated for association with coronary artery calcium (CAC) prevalence, CAC extent, total plaque score, and total segment stenosis using multivariable regression. RESULTS: Of the 504 participants, 384 were men with HIV (MWH) and 120 were men without HIV. In models adjusted for sociodemographic factors, cardiovascular disease risk factors, eGFR, and HIV-related factors, each two-fold higher concentration of albuminuria was associated with a greater extent of CAC (1.35-fold higher, 95% confidence interval 1.11-1.65), and segment stenosis (1.08-fold greater, 95% confidence interval 1.01-1.16). Associations were similar between MWH and men without HIV in stratified analyses. The third quartile of A1 M showed an association with greater CAC extent, total plaque score, and total segment stenosis, compared with the lowest quartile. CONCLUSION: Worse endothelial and proximal tubule dysfunction, as reflected by higher urine albumin and A1 M, were associated with greater CAC extent and coronary artery stenosis.


Subject(s)
Cardiovascular Diseases , Coronary Artery Disease , HIV Infections , Plaque, Atherosclerotic , Male , Humans , Female , HIV Infections/complications , HIV Infections/epidemiology , Coronary Artery Disease/epidemiology , Cardiovascular Diseases/complications , Cohort Studies , Albuminuria , Cross-Sectional Studies , Constriction, Pathologic/complications , Risk Factors , Kidney , Biomarkers
6.
Am J Gastroenterol ; 119(4): 768-773, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38131623

ABSTRACT

INTRODUCTION: We determined steatotic liver disease (SLD) incidence in a prospective cohort of men with HIV (MWH) and men without HIV (MWOH). METHODS: Incident SLD was defined using paired noncontrast computed tomography scans performed during 2010-2013 and repeated during 2015-2017. RESULTS: Of 268 men, 173 MWH and 95 MWOH, 33 had incident SLD (11.1%, incidence rate 2.4 and 2.7/100 person-years for MWH and MWOH, respectively). Overall, higher abdominal visceral adipose tissue was independently associated with increased SLD risk. In MWH, increased visceral adipose tissue, insulin resistance, chronic hepatitis B, and cumulative etravirine use were associated with SLD. DISCUSSION: Metabolic factors, but not HIV, were associated with incident SLD. The high incidence rate suggests that SLD will continue to increase in PWH.


Subject(s)
Fatty Liver , HIV Infections , Male , Humans , HIV Infections/complications , HIV Infections/epidemiology , Incidence , Prospective Studies , Fatty Liver/diagnostic imaging , Fatty Liver/epidemiology , Fatty Liver/complications , Tomography/adverse effects
7.
Proc Natl Acad Sci U S A ; 120(49): e2306788120, 2023 Dec 05.
Article in English | MEDLINE | ID: mdl-38032935

ABSTRACT

Phagocytosis is a critical immune function for infection control and tissue homeostasis. During phagocytosis, pathogens are internalized and degraded in phagolysosomes. For pathogens that evade immune degradation, the prevailing view is that virulence factors are required to disrupt the biogenesis of phagolysosomes. In contrast, we present here that physical forces from motile pathogens during cell entry divert them away from the canonical degradative pathway. This altered fate begins with the force-induced remodeling of the phagocytic synapse formation. We used the parasite Toxoplasma gondii as a model because live Toxoplasma actively invades host cells using gliding motility. To differentiate the effects of physical forces from virulence factors in phagocytosis, we employed magnetic forces to induce propulsive entry of inactivated Toxoplasma into macrophages. Experiments and computer simulations show that large propulsive forces hinder productive activation of receptors by preventing their spatial segregation from phosphatases at the phagocytic synapse. Consequently, the inactivated parasites are engulfed into vacuoles that fail to mature into degradative units, similar to the live motile parasite's intracellular pathway. Using yeast cells and opsonized beads, we confirmed that this mechanism is general, not specific to the parasite used. These results reveal new aspects of immune evasion by demonstrating how physical forces during active cell entry, independent of virulence factors, enable pathogens to circumvent phagolysosomal degradation.


Subject(s)
Parasites , Toxoplasma , Animals , Virus Internalization , Phagocytosis , Macrophages , Virulence Factors
8.
AIDS ; 37(10): 1555-1564, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37352493

ABSTRACT

OBJECTIVE: Marijuana, tobacco and alcohol use are prevalent among people with HIV and may adversely affect kidney function in this population. We determined the association of use of these substances with estimated glomerular filtration rate (eGFR) among women with HIV (WWH) and women without HIV. DESIGN: We undertook a repeated measures study of 1043 WWH and 469 women without HIV within the United States Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-seropositive and HIV-seronegative women. METHODS: We quantified substance exposures using semi-annual questionnaires. Using pooled eGFR data from 2009 to 2019, we used linear regression models with multivariable generalized estimating equations to ascertain associations between current and cumulative substance use exposures with eGFR, adjusting for sociodemographics, chronic kidney disease risk factors and HIV-related factors. RESULTS: Marijuana use of 1-14 days/month versus 0 days/month was associated with 3.34 ml/min per 1.73 m 2 [95% confidence interval (CI) -6.63, -0.06] lower eGFR and marijuana use of >0.02-1.6 marijuana-years versus 0-0.2 marijuana-years was associated with 3.61 ml/min per 1.73 m 2 (95% CI -5.97, -1.24) lower eGFR. Tobacco use was not independently associated with eGFR. Alcohol use of seven or more drinks/week versus no drinks/week was associated with 5.41 ml/min per 1.73 m 2 (95% CI 2.34, 8.48) higher eGFR and alcohol use of >0.7-4.27 drink-years and >4.27 drink-years versus 0-0.7 drink-years were associated with 2.85 ml/min per 1.73 m 2 (95% CI 0.55, 5.15) and 2.26 ml/min per 1.73 m 2 (95% CI 0.33, 4.20) higher eGFR, respectively. CONCLUSION: Among a large cohort of WWH and women without HIV, marijuana use was associated with a lower eGFR while alcohol use was associated with a higher eGFR.


Subject(s)
Cannabis , HIV Infections , Substance-Related Disorders , Humans , Female , United States/epidemiology , Glomerular Filtration Rate , HIV Infections/epidemiology , Prospective Studies , Substance-Related Disorders/complications
9.
Biomacromolecules ; 24(6): 2479-2488, 2023 06 12.
Article in English | MEDLINE | ID: mdl-37224421

ABSTRACT

A large repertoire of nanocarrier (NC) technologies exists, each with highly specified advantages in terms of targetability, stability, and immunological inertness. The characterization of such NC properties within physiological conditions is essential for the development of optimized drug delivery systems. One method that is well established for reducing premature elimination by avoiding protein adsorption on NCs is surface functionalization with poly(ethylene glycol) (PEG), aptly called PEGylation. However, recent studies revealed that some PEGylated NCs have a delayed immune response, indicating the occurrence of protein-NC interactions. Obvious protein-NC interactions, especially in micellar systems, may have been overlooked as many early studies relied on techniques less sensitive to molecular level interactions. More sensitive techniques have been developed, but a major challenge is the direct measurement of interactions, which must be done in situ, as micelle assemblies are dynamic. Here, we report the use of pulsed-interleaved excitation fluorescence cross-correlation spectroscopy (PIE-FCCS) to interrogate the interactions between two PEG-based micelle models and serum albumin protein to compare protein adsorption differences based on linear or cyclic PEG architectures. First, by measuring micelle diffusion in isolated and mixed solutions, we confirmed the thermal stability of diblock and triblock copolymer micelle assemblies. Further, we measured the co-diffusion of micelles and serum proteins, the magnitudes of which increased with concentration and continued incubation. The results demonstrate that PIE-FCCS is capable of measuring direct interactions between fluorescently labeled NC and serum proteins, even at concentrations 500 times lower than those observed physiologically. This capability showcases the potential utility of PIE-FCCS in the characterization of drug delivery systems in biomimetic conditions.


Subject(s)
Micelles , Polymers , Polymers/chemistry , Polyethylene Glycols/chemistry , Drug Delivery Systems , Proteins/chemistry
10.
Cureus ; 15(4): e37227, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37168206

ABSTRACT

Complex regional pain syndrome (CRPS) is a rare disorder that presents as a highly variable combination of intense regional pain, autonomic and vasomotor disturbances that are uncharacteristic of the inciting trauma or event. We report a 36-year-old male construction worker who presented to the orthopedic department status post crush injury to his hand, with acutely increasing right-hand pain, swelling, skin/hair changes, and dysfunction. Presentation changed over a course of 2-8 weeks, with CRPS becoming the eventual working diagnosis. Initial diagnoses were not made by occupational med, nor the urgent care, and definitive diagnosis was achieved in the orthopedic hand office via a thorough history and physical exam as well as imaging modalities including X-ray, CT, and MRI. A multidisciplinary approach involving aggressive hand therapy, anti-inflammatory agents, high-dose prednisone, Gabapentin, and over-the-counter vitamins and supplements was used in the treatment of this patient. This patient had a unique progression of his condition with respect to his carpus, demonstrating acute reduction of bone density on plain film. Stiffness ensued. This patient's condition was almost "missed" by the masking of the ulnar ossicle variant (os triangulare), and anatomical snuffbox pain on exam, in the face of initially "normal" X-rays. It is important for providers to recognize the clinical signs of complex regional pain syndrome, especially in the acute phase of crush injury, swelling, skin and hair changes, and stiffness, and to treat patients' symptoms with a variety of treatment options due to the marked variability of this condition. The patient has made a favorable recovery with some residual functional deficits, however, the patient stated that his quality of life has been restored despite his current stiffness.

11.
bioRxiv ; 2023 Apr 28.
Article in English | MEDLINE | ID: mdl-37162866

ABSTRACT

Phagocytosis is a critical immune function for infection control and tissue homeostasis. This process is typically described as non-moving pathogens being internalized and degraded in phagolysosomes. For pathogens that evade immune degradation, the prevailing view is that virulence factors that biochemically disrupt the biogenesis of phagoslysosomes are required. In contrast, here we report that physical forces exerted by pathogens during cell entry divert them away from the canonical phagolysosomal degradation pathway, and this altered intracellular fate is determined at the time of phagocytic synapse formation. We used the eukaryotic parasite Toxoplasma gondii as a model because live Toxoplasma uses gliding motility to actively invade into host cells. To differentiate the effect of physical forces from that of virulence factors in phagocytosis, we developed a strategy that used magnetic forces to induce propulsive entry of inactivated Toxoplasma into macrophage cells. Experiments and computer simulations collectively reveal that large propulsive forces suppress productive activation of receptors by hindering their spatial segregation from phosphatases at the phagocytic synapse. Consequently, the inactivated parasites, instead of being degraded in phagolysosomes, are engulfed into vacuoles that fail to mature into degradative units, following an intracellular pathway strikingly similar to that of the live motile parasite. Using opsonized beads, we further confirmed that this mechanism is general, not specific to the parasite used. These results reveal previously unknown aspects of immune evasion by demonstrating how physical forces exerted during active cell entry, independent of virulence factors, can help pathogens circumvent phagolysosomal degradation.

12.
Cureus ; 14(7): e27480, 2022 Jul.
Article in English | MEDLINE | ID: mdl-36060368

ABSTRACT

Chronic exertional compartment syndrome is a reversible form of compartment syndrome that occurs with exertion and is relieved with rest. Chronic exertional compartment syndrome most commonly occurs in the lower leg and has only rarely been reported in the hand. We report a case of exertional compartment syndrome in the left hand of a 37-year-old male heavy equipment technician with concurrent carpal tunnel syndrome and ulnar neuropathy. Physical examination showed non-exertional numbness and tingling in all five digits while at rest with a reproducible Tinel's test over the carpal tunnel and Guyon's canal. Acute swelling and hand muscle weakness appeared after repetitive pinch and usage of the thenar and intrinsic musculature with acute sensory and motor changes in the ulnar nerve distribution. Elective fasciotomies were performed in the first dorsal interosseous and thenar compartments with concomitant release of the carpal tunnel and ulnar nerve at the wrist. The patient exhibited a full recovery from symptoms with no residual functional deficits. Although rare, patients that perform repetitive hand motions can develop chronic exertional compartment syndrome. To our knowledge, this is the first reported case of chronic exertional compartment syndrome in the hand that occurred with chronic overuse neuropathies and an acute ulnar neuropathy with intrinsic hand muscle weakness at the same time. It is important for providers to conduct a thorough history and physical examination to differentiate multiple hand pathologies that may present simultaneously.

13.
AIDS ; 36(11): 1553-1562, 2022 09 01.
Article in English | MEDLINE | ID: mdl-35979829

ABSTRACT

OBJECTIVE: To use accelerometers to quantify differences in physical activity (PA) by HIV serostatus and HIV viral load (VL) in the Multicenter AIDS Cohort Study (MACS). METHODS: MACS participants living with (PLWH, n = 631) and without (PWOH, n = 578) HIV wore an ambulatory electrocardiogram monitor containing an accelerometer for 1-14 days. PA was summarized as cumulative mean absolute deviation (MAD) during the 10 most active consecutive hours (M10), cumulative MAD during the six least active consecutive hours (L6), and daily time recumbent (DTR). PA summaries were compared by HIV serostatus and by detectability of VL (>20 vs. ≤20 copies/ml) using linear mixed models adjusted for sociodemographics, weight, height, substance use, physical function, and clinical factors. RESULTS: In sociodemographic-adjusted models, PLWH with a detectable VL had higher L6 (ß = 0.58 mg, P = 0.027) and spent more time recumbent (ß = 53 min/day, P = 0.003) than PWOH. PLWH had lower M10 than PWOH (undetectable VL ß = -1.62 mg, P = 0.027; detectable VL ß = -1.93 mg, P = 0.12). A joint test indicated differences in average PA measurements by HIV serostatus and VL (P = 0.001). However, differences by HIV serostatus in M10 and DTR were attenuated and no longer significant after adjustment for renal function, serum lipids, and depressive symptoms. CONCLUSIONS: Physical activity measures differed significantly by HIV serostatus and VL. Higher L6 among PLWH with detectable VL may indicate reduced amount or quality of sleep compared to PLWH without detectable VL and PWOH. Lower M10 among PLWH indicates lower amounts of physical activity compared to PWOH.


Subject(s)
HIV Infections , Substance-Related Disorders , Cohort Studies , Exercise , Humans , Male , Viral Load
14.
Atherosclerosis ; 353: 33-40, 2022 07.
Article in English | MEDLINE | ID: mdl-35577614

ABSTRACT

BACKGROUND AND AIMS: People living with HIV (HIV+) are surviving longer due to effective antiretroviral therapy. Cardiovascular disease is a leading cause of non-AIDS related clinical events. We determined HIV-related factors associated with coronary artery stenosis progression. METHODS: We performed serial coronary CT angiography among HIV+ and HIV-uninfected (HIV-) men in the Multicenter AIDS Cohort Study. The median inter-scan interval was 4.5 years. Stenosis was graded as 0, 1-29, 30-49, 50-69 or ≥70%. Progression was defined as an increase ≥2 categories. Suppressed HIV infection was consistent viral loads <50 copies/mL allowing 1 "blip" <500 copies/mL, otherwise considered viremic. Multivariable Poisson regression analysis assessed adjusted associations between HIV serostatus and viremia with coronary stenosis progression. RESULTS: The sample included 310 HIV+ (31% viremic) and 234 HIV- men. The median age was 53 years, 30% Black and 23% current smokers. Viremic men were 2.3 times more likely to develop coronary stenosis progression than HIV- men (adjusted RR 2.30; 95% CI, 1.32-4.00, p = 0.003), with no difference in progression between HIV+ suppressed and HIV- men (RR 1.10; 95% CI, 0.70-1.74, p = 0.67). There was a progressive increase in adjusted relative risk with greater viremia (p = 0.03). Men with >1 viral load >500 copies/ml demonstrated greatest stenosis progression (RR 3.01; 95% CI, 1.53-4.92, p = 0.001 compared with HIV- men). Suppressed HIV+ men with suboptimal antiretroviral adherence had greater stenosis progression (RR 1.91; 95% CI 1.12-3.24, p = 0.02) than HIV + suppressed men with optimal adherence. CONCLUSIONS: Coronary artery stenosis progression was associated with suboptimal HIV RNA suppression and antiretroviral therapy adherence. Effective ongoing HIV virologic suppression and antiretroviral therapy adherence may mitigate risk for coronary disease events among people living with HIV.


Subject(s)
Coronary Artery Disease , Coronary Stenosis , HIV Infections , Cohort Studies , Computed Tomography Angiography , Constriction, Pathologic , Coronary Angiography , Coronary Artery Disease/complications , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Coronary Stenosis/complications , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/epidemiology , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Male , Middle Aged , Viremia
17.
Article in English | MEDLINE | ID: mdl-34542321

ABSTRACT

Chronic inflammation, including among people with HIV (PWH), elevates immune cell expression of lymphocyte activation gene 3 (LAG3); however, low plasma LAG3 predicts cardiovascular disease (CVD) events in the general population. The associations among LAG3 plasma levels, subclinical atherosclerosis, inflammation, and HIV infection have not been well described. We measured plasma LAG3 in 704 men with and without HIV from the multicenter AIDS cohort study, who underwent coronary computed tomography angiography. HIV serostatus was not independently associated with LAG3 after adjustment for sociodemographic and CVD risk factors. Current smoking status and African American race were associated with lower LAG3, and age and sTNFαRI concentration were associated with greater LAG3. LAG3 was not associated with coronary artery stenosis. Thus, no difference was found in plasma LAG3 concentration by HIV serostatus, and no association between LAG3 and subclinical coronary atherosclerosis in men with and without HIV was observed.

18.
Biomimetics (Basel) ; 6(3)2021 Sep 18.
Article in English | MEDLINE | ID: mdl-34562876

ABSTRACT

Critically sized defects in subcutaneous white adipose tissue result in extensive disfigurement and dysfunction and remain a reconstructive challenge for surgeons; as larger defect sizes are correlated with higher rates of complications and failure due to insufficient vascularization following implantation. Our study demonstrates, for the first time, a method to engineer perfusable, pre-vascularized, high-density adipose grafts that combine patient-derived adipose cells with a decellularized lung matrix (DLM). The lung is one of the most vascularized organs with high flow, low resistance, and a large blood-alveolar interface separated by a thin basement membrane. For our work, the large volume capacity within the alveolar compartment was repurposed for high-density adipose cell filling, while the acellular vascular bed provided efficient graft perfusion throughout. Both adipocytes and hASCs were successfully delivered and remained in the alveolar space even after weeks of culture. While adipose-derived cells maintained their morphology and functionality in both static and perfusion DLM cultures, perfusion culture offered enhanced outcomes over static culture. Furthermore, we demonstrate that endothelial cells seamlessly integrate into the acellular vascular tree of the DLM with adipocytes. These results support that the DLM is a unique platform for creating vascularized adipose tissue grafts for large defect filling.

19.
Medicine (Baltimore) ; 100(29): e26663, 2021 Jul 23.
Article in English | MEDLINE | ID: mdl-34398028

ABSTRACT

ABSTRACT: Atrial fibrillation (AF) leads to increased risk for stroke. Human immunodeficiency virus (HIV) is associated with cardiovascular disease (CVD), although it is unclear if HIV is associated with AF. The purpose of this study was to evaluate the association between HIV serostatus and the prevalence of AF in the Multicenter AIDS Cohort Study.A cross sectional study was conducted among 1674 HIV-infected (HIV+) and uninfected (HIV-) men who completed resting 12-lead electrocardiograms, and/or ambulatory electrocardiogram monitoring. Multivariable logistic regression was used to evaluate the association between AF, defined as the presence of either AF or atrial flutter, and HIV+ serostatus. Associations were adjusted for demographic variables, and then also for CVD risk factors.HIV+ men were younger than HIV- men (median 55.5 vs 61.7 years, P < .001) and were more frequently African-American (30.5% vs 17.8%, P < .001). Most HIV+ men (81%) had undetectable viral load. The age and race adjusted prevalence of AF was 3.0% in HIV+ and 3.3% in HIV- men. There was only 1 case of AF among African-American men. There were no associations between AF and HIV serostatus after adjusting for demographic factors (odds ratio 0.76; 95% CI 0.37 to -1.58; P = .47) or after further adjustment for CVD risk factors (odds ratio 0.84; 95% CI 0.39 to -1.81; P = .66).We found no association between HIV and AF in this cohort in which viral replication among the HIV+ men is generally suppressed. The overall prevalence of AF was low and was rare in African-American men.


Subject(s)
Atrial Fibrillation/epidemiology , HIV Infections , Adolescent , Adult , Age Factors , Aged , Atrial Fibrillation/ethnology , Atrial Fibrillation/etiology , Cross-Sectional Studies , Ethnicity , Humans , Male , Middle Aged , Prevalence , Risk Factors , United States/epidemiology , Viral Load , Young Adult
20.
AIDS Res Hum Retroviruses ; 37(11): 842-845, 2021 11.
Article in English | MEDLINE | ID: mdl-34384260

ABSTRACT

Chronic inflammation, including among people with HIV (PWH), elevates immune cell expression of lymphocyte activation gene 3 (LAG3); however, low plasma LAG3 predicts cardiovascular disease (CVD) events in the general population. The associations among LAG3 plasma levels, subclinical atherosclerosis, inflammation, and HIV infection have not been well described. We measured plasma LAG3 in 704 men with and without HIV from the multicenter AIDS cohort study, who underwent coronary computed tomography angiography. HIV serostatus was not independently associated with LAG3 after adjustment for sociodemographic and CVD risk factors. Current smoking status and African American race were associated with lower LAG3, and age and sTNFαRI concentration were associated with greater LAG3. LAG3 was not associated with coronary artery stenosis. Thus, no difference was found in plasma LAG3 concentration by HIV serostatus, and no association between LAG3 and subclinical coronary atherosclerosis in men with and without HIV was observed.


Subject(s)
Acquired Immunodeficiency Syndrome , Coronary Artery Disease , HIV Infections , Antigens, CD/genetics , Antigens, CD/metabolism , Cohort Studies , Coronary Artery Disease/diagnostic imaging , HIV Infections/complications , Humans , Lymphocyte Activation , Male , Lymphocyte Activation Gene 3 Protein
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