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1.
Circulation ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31707799

RESUMO

Background: People living with human immunodeficiency virus (HIV+) have greater risk for sudden arrhythmic death than HIV-uninfected (HIV-) individuals. HIV-associated abnormal cardiac repolarization may contribute to this risk. We investigated whether HIV serostatus is associated with ventricular repolarization lability using QT variability index (QTVI), defined as a log measure of QT interval variance indexed to heart rate (HR) variance. Methods: We studied 1123 men (589 HIV+ and 534 HIV-) from the Multicenter AIDS Cohort Study (MACS), using the ZioXT® ambulatory electrocardiography (ECG) patch. Beat-to-beat analysis of up to 4 full days of ECG data per participant were performed using an automated algorithm [median analyzed duration (Q1-Q3): 78.3 (66.3-83.0) hours/person]. QTVI was modeled using linear mixed-effects models adjusted for demographics, cardiac risk factors, and HIV-related and inflammatory biomarkers. Results: Mean (SD) age was 60.1 (11.9) years among HIV- and 54.2 (11.2) years among HIV+ participants (p<0.001), 83% of whom had undetectable (<20 copies/mL) HIV-1 viral load (VL). Compared to HIV- men, HIV+ men had higher QTVI [adjusted difference of +0.077 (95% CI: +0.032 to +0.123)]. Magnitude of this association depended on the degree of viremia such that in HIV+ men with undetectable VL, adjusted QTVI was +0.064 (95% CI: +0.017 to +0.111) higher compared to HIV- men, while in HIV+ men with detectable VL adjusted QTVI was higher by +0.150 (95% CI: 0.072-0.228) compared to HIV- referents. Analysis of QTVI subcomponents showed HIV+ men had: (1) lower HR variability irrespective of VL status, and (2) higher QT variability if they had detectable-but not with undetectable-VL, when compared to HIV- men. Higher levels of C-reactive protein (CRP), interleukin-6 (IL-6), intercellular adhesion molecule (ICAM)-1, soluble tumor necrosis factor (TNF)-receptor 2, and soluble cluster of differentiation (CD)-163 (borderline), were associated with higher QTVI and partially attenuated the association with HIV serostatus. Conclusions: HIV+ men have greater beat-to-beat variability in QT interval (QTVI) compared to HIV- men, especially in the setting of HIV viremia and heightened inflammation. Among HIV+ men, higher QTVI suggests ventricular repolarization lability which can increase susceptibility to arrhythmias, while lower HR variability signals a component of autonomic dysfunction.

2.
Clin Infect Dis ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31606734

RESUMO

BACKGROUND: Initiation of antiretroviral therapy (ART) often leads to weight gain. While some of this weight gain may be an appropriate return-to-health effect, excessive increases in weight may lead to obesity. We sought to explore factors associated with weight gain in several randomized comparative clinical trials of ART initiation. METHODS: We performed a pooled analysis of weight gain in 8 randomized controlled clinical trials of treatment-naïve people with HIV (PWH) initiating ART between 2003-2015, comprising over 5,000 participants and 10,000 person-years of follow-up. We used multivariate modeling to explore relationships between demographic factors, HIV disease characteristics, and ART components and weight change following ART initiation. FINDINGS: Weight gain was greater in more recent trials and with the use of newer ART regimens. Pooled analysis revealed baseline demographic factors associated with weight gain including lower CD4, higher HIV-1 RNA, no injection drug use, female sex and black race. Integrase strand transfer inhibitors (INSTIs) were associated with more weight gain than protease inhibitors or non-nucleoside reverse transcriptase inhibitors (NNRTI), with dolutegravir and bictegravir associated with more weight gain than elvitegravir/cobicistat. Among the NNRTIs, rilpivirine was associated with more weight gain than efavirenz. Among nucleoside/nucleotide reverse transcriptase inhibitors, tenofovir alafenamide was associated with more weight gain than tenofovir disoproxil fumarate, abacavir, or zidovudine. INTERPRETATION: Weight gain is ubiquitous in clinical trials of ART initiation, and is multifactorial in nature, with demographic factors, HIV-related factors, and the composition of ART regimens contributing. The mechanisms by which certain ART agents differentially contribute to weight gain are unknown.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31564631

RESUMO

BACKGROUND: The purpose of this study is to determine if a new score calculated with coronary artery calcium (CAC) density and volume is associated with total coronary artery plaque burden and composition on coronary CT angiography (CCTA) compared to the Agatston score (AS). METHODS: We identified 347 men enrolled in the Multicenter AIDS cohort study who underwent contrast and non-contrast CCTs, and had CAC>0. CAC densities (mean Hounsfield Units [HU]) per plaque) and volumes on non-contrast CCT were measured. A Density-Volume Calcium score was calculated by multiplying the plaque volume by a factor based on the mean HU of the plaque (4, 3, 2 and 1 for 130-199, 200-299, 300-399, and ≥400HU). Total Density-Volume Calcium score was determined by the sum of these individual scores. The semi-quantitative partially calcified and total plaque scores (PCPS and TPS) on CCTA were calculated. The associations between Density-Volume Calcium score, PCPS and TPS were examined. RESULTS: Overall, 2879 CAC plaques were assessed. Multivariable linear regression models demonstrated a stronger association between the log Density-Volume Calcium score and both the PCPS (ß 0.99, 95%CI 0.80-1.19) and TPS (ß 2.15, 95%CI 1.88-2.42) compared to the log of AS (PCPS: ß 0.77, 95%CI 0.61-0.94; TPS: ß 1.70, 95%CI 1.48-1.94). Similar results were observed for numbers of PC or TP segments. CONCLUSION: The new CAC score weighted towards lower density demonstrated improved correlation with semi-quantitative PC and TP burden on CCTA compared to the traditional AS, which suggests it has utility as an alternative measure of atherosclerotic burden.

4.
Ann Noninvasive Electrocardiol ; : e12705, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31538387

RESUMO

BACKGROUND: The total QT interval comprises both ventricular depolarization and repolarization currents. Understanding how HIV serostatus and other risk factors influence specific QT interval subcomponents could improve our mechanistic understanding of arrhythmias. METHODS: Twelve-lead electrocardiograms (ECGs) were acquired in 774 HIV-infected (HIV+) and 652 HIV-uninfected (HIV-) men from the Multicenter AIDS Cohort Study. Individual QT subcomponent intervals were analyzed: R-onset to R-peak, R-peak to R-end, JT segment, T-onset to T-peak, and T-peak to T-end. Using multivariable linear regressions, we investigated associations between HIV serostatus and covariates, including serum concentrations of inflammatory biomarkers such as interleukin-6 (IL-6), and each QT subcomponent. RESULTS: After adjustment for demographics and risk factors, HIV+ versus HIV- men differed only in repolarization phase durations with longer T-onset to T-peak by 2.3 ms (95% CI 0-4.5, p < .05) and T-peak to T-end by 1.6 ms (95% CI 0.3-2.9, p < .05). Adjusting for inflammation attenuated the strength and significance of the relationship between HIV serostatus and repolarization. The highest tertile of IL-6 was associated with a 7.3 ms (95% CI 3.2-11.5, p < .01) longer T-onset to T-peak. Age, race, body mass index, alcohol use, and left ventricular hypertrophy were each associated with up to 2.2-12.5 ms longer T-wave subcomponents. CONCLUSIONS: HIV seropositivity, in combination with additional risk factors including increased systemic inflammation, is associated with longer T-wave subcomponents. These findings could suggest mechanisms by which the ventricular repolarization phase is lengthened and thereby contribute to increased arrhythmic risk in men living with HIV.

5.
J Neurovirol ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31468473

RESUMO

The AIDS Clinical Trials Group (ACTG) study A5303 investigated the associations between neuropsychological performance (NP) and inflammatory biomarkers in HIV-infected participants. Fifteen NP tests were administered at baseline and week 48 to 233 ART naïve participants randomized to maraviroc- or tenofovir-containing ART. Neurocognition correlated modestly with markers of lymphocyte activation and inflammation pre-ART (percent CD38+/HLA-DR+(CD4+) (r = - 0.22, p = 0.02) and percent CD38+/HLA-DR+(CD8+) (r = - 0.25, p = 0.02)), and with some monocyte subsets during ART (r = 0.25, p = 0.02). Higher interleukin-6 and percent CD38+/HLA-DR+(CD8+) were independently associated with worse severity of HIV-associated neurocognitive disorders (HAND) (p = 0.04 and 0.01, respectively). More studies to identify HAND biomarkers are needed.

6.
AIDS Res Hum Retroviruses ; 35(11-12): 1065-1073, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468979

RESUMO

Gait speed declines at a faster rate in persons with HIV (PWH) than in the general population but the risk factors associated with this decline are not well understood. In the AIDS Clinical Trials Group (ACTG) A5322 (HAILO, HIV Infection, Aging, and Immune Function Long-term Observational Study), an observational cohort study of PWH ≥40 years of age, those who developed slow gait during the first 3 years of follow-up were compared with persons who maintained normal speed. Associations with demographic and clinical covariates were assessed using multivariable logistic regression. Of 929 participants, 81% were men, 31% Black, and 20% Hispanic. Median age was 51 years [interquartile range (IQR) = 46-56]. At study entry, 92% had plasma HIV RNA <50 copies/mL with median CD4 count 631 cells/mm3 (IQR = 458-840). At study entry, 7% of participants had slow gait, 16% had neurocognitive impairment (NCI), and 12% had diabetes. Over 3 years, 87% maintained normal gait speed, 3% maintained a slow gait, 6% developed a slow gait, and 4% improved from slow to normal gait speed. In multivariable models, hemoglobin A1C (HbA1C) percentage, per one unit increase [odds ratio (OR) = 1.36; 95% confidence interval (CI) = 1.03-1.81; p = .033], NCI (OR = 3.47; 95% CI = 1.57-7.69 p = .002), and black versus white race (OR = 2.45; 95% CI = 1.08-5.59; p = .032) at entry were significantly associated with development of slow gait compared with those maintaining normal gait speed. The association between baseline HbA1C and development of slow gait speed highlights an intervenable target to prevent progression of physical function limitations.

7.
J Clin Endocrinol Metab ; 104(10): 4857-4864, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31329901

RESUMO

CONTEXT: Microscopic measurement of adipocyte size is the gold standard for determining adipose tissue (AT) quality. AT density on CT may also reflect adipocyte quality (lower density = poorer quality). OBJECTIVE: We used abdominal subcutaneous AT (SAT) specimens and CT scans to validate CT SAT density as a marker of SAT quality in adults living with HIV. SETTING AND DESIGN: Secondary data analysis from completed trial of antiretroviral therapy (ART) initiation (ACTG A5224s). CT abdominal SAT density was measured in HU. SAT specimens were digitally scanned for calculation of mean adipocyte area. PARTICIPANTS: Participants had SAT biopsy and CT data at baseline (n = 54) and HIV-1 RNA <50 copies per milliliter on ART and biopsy or CT data at week 96 (n = 30). OUTCOME MEASURES: Spearman correlations and linear regression models adjusting for participant characteristics examined associations between SAT density and adipocyte area. RESULTS: Baseline median age was 40 years, CD4+ T lymphocyte count 219 cells per cubic millimeter, and body mass index 26.0 kg/m2; 89% were male and 67% white. Median SAT area and density were 199 cm2 and -100 HU. Over 96 weeks, SAT area increased (+18%) and SAT density decreased (-3%). Mean SAT adipocyte area correlated with SAT density (P < 0.01) off and on ART after adjustment for SAT area, age, race, sex, CD4+ T lymphocyte count, and HIV-1 RNA. CONCLUSIONS: CT SAT density correlates with biopsy-quantified SAT adipocyte size in adults with HIV on and off ART, suggesting that CT is a useful tool for noninvasive assessment of SAT quality.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31287490

RESUMO

INTRODUCTION: "Frailty" has attracted attention for its promise of identifying vulnerable older adults, hence its potential use to better tailor geriatric health care. There remains substantial controversy, however, regarding its nature and ascertainment. Recent years have seen a proliferation of frailty assessment methods. We argue that the development of frailty assessments should be grounded in "validation"-the process of substantiating that a measurement accurately and precisely measures what it intends, identify unresolved measurement issues, and highlight measurement-related considerations for clinical practice. METHODS: Principles for validating frailty measures are elucidated. We follow principles-articulated, for example, by Borsboom-in which a construct must be clearly defined and then analyses undertaken to substantiate that a measurement accurately and precisely measures what it intends. Key elements are content validity, criterion validity, and construct validity, with an emphasis on the latter. RESULTS: We illustrate the principles for a physical frailty phenotype construct. CONCLUSIONS: Unresolved conceptual issues include the roles of intersecting concepts such as cognition, disease severity, and disability in frailty measurement, conceptualization of frailty as a state versus a continuum, and the potential need for dynamic measures and systems concepts in furthering understanding of frailty. Clinical considerations include needs to distinguish interventions designed to address frailty "symptoms" versus underlying physiology, improve "pre-frailty" measures intended to screen individuals early in their frailty progression, address feasibility demands, and further visioning followed by rigorous efficacy research to address the landscape of potential uses of frailty assessment in clinical practice.

9.
J Acquir Immune Defic Syndr ; 81(4): e117-e126, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31242143

RESUMO

BACKGROUND: Falls and fall risk factors are common among people living with HIV (PLWH). We sought to identify fall risk factors among men with and without HIV. METHODS: Men aged 50-75 years with (n = 279) and without HIV (n = 379) from the Bone Strength Substudy of the Multicenter AIDS Cohort Study were included. Multinomial logistic regression models identified risk factors associated with falling. RESULTS: One hundred fourteen (41%) PLWH and 149 (39%) of uninfected men had ≥1 fall; 54 (20%) PLWH and 66 (17%) of uninfected men experienced ≥2 falls over 2 years. Five and 3% of PLWH and uninfected men, respectively, had a fall-related fracture (P = 0.34). In multivariate models, the odds of ≥2 falls were greater among men reporting illicit drug use, taking diabetes or depression medications, and with peripheral neuropathy; obesity was associated with a lower risk (all P < 0.05). In models restricted to PLWH, detectable plasma HIV-1 RNA, current use of efavirenz or diabetes medications, illicit drug use, and peripheral neuropathy were associated with greater odds of having ≥2 falls (P < 0.05). Current efavirenz use was associated with increased odds of an injurious fall; longer duration of antiretroviral therapy was protective (both P < 0.05). Greater physical activity was associated with lower risk of falls with fracture (P < 0.05). CONCLUSIONS: Identified risk factors for recurrent falls or fall with fracture included low physical activity, detectable HIV-1 RNA, use of efavirenz, or use of medications to treat diabetes and depression. Fall risk reduction should prioritize interventions targeting modifiable risk factors including increased physical activity, antiretroviral therapy adherence, and transition off efavirenz.

10.
Neurology ; 93(3): e261-e271, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31201294

RESUMO

OBJECTIVE: Obesity is a common, modifiable cardiovascular and cerebrovascular risk factor. Among people with HIV, obesity may contribute to multisystem dysregulation including cognitive impairment. We examined body mass index (BMI) and central obesity (waist circumference [WC]) in association with domain-specific cognitive function and 10-year cognitive decline in men with HIV infection (MWH) vs HIV-uninfected (HIV-) men. METHODS: A total of 316 MWH and 656 HIV- Multicenter AIDS Cohort Study participants ≥40 years at baseline, with neuropsychological testing every 2 years and concurrent BMI and WC measurements, were included. MWH were included if taking ≥2 antiretroviral agents and had HIV-1 RNA <400 copies/mL at >80% of visits. Mixed-effects models included all visits from 1996 to 2015, stratified by HIV serostatus, and adjusted for sociodemographic, behavioral, and clinical characteristics. At baseline and follow-up, 8% of MWH and 15% of HIV- men and 41% of MWH and 56% of HIV- men were ≥60 years, respectively. RESULTS: Cross-sectionally, higher BMI was inversely associated with motor function in MWH and HIV- men, and attention/working memory in HIV- men. WC was inversely associated with motor function in MWH and HIV- men. Longitudinal associations indicated an obese BMI was associated with a less steep decline in motor function in MWH whereas in HIV- men, obesity was associated with a greater decline in motor function, learning, and memory. WC, or central obesity, showed similar patterns of associations. CONCLUSION: Higher adiposity is associated with lower cognition cross-sectionally and greater cognitive decline, particularly in HIV- men. Overweight and obesity may be important predictors of neurologic outcomes and avenues for prevention and intervention.

11.
AIDS ; 33(10): 1669-1671, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31082861

RESUMO

: Heightened systemic inflammation contributes to cardiovascular (CVD) events in people living with HIV (PLWH), although not all PLWH develop CVD, thus suggesting a genetic modifying role. We examined GCH1 polymorphisms, which have been associated with reduced endothelial function in European populations with CVD and increased inflammation, in a racially diverse cohort of US PLWH initiating antiretroviral therapy (ART). GCH1 polymorphisms differed by race and were not associated with flow-mediated dilation or carotid intima-media thickness before or after 48 weeks of ART.

12.
Clin Infect Dis ; 2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-31131846

RESUMO

BACKGROUND: Effective concentrations of antiretrovirals in the female genital tract (FGT) are critical for suppression of viral shedding or effective pre-exposure prophylaxis. The disposition of tenofovir diphosphate (TFVdp) and emtricitabine triphosphate (FTCtp) in the FGT have been previously described. Despite widespread use, however, lamivudine triphosphate (3TCtp) exposure in FGT is unknown. Depot medroxyprogesterone acetate (DMPA) and vaginal dysbiosis have been implicated in increased risk of HIV acquisition but whether they alter TFVdp or 3TCtp exposure, and therefore compromise prevention efficacy, is unknown. METHODS: Fifty pre-menopausal women living with HIV in Kampala, Uganda and receiving daily tenofovir disoproxil fumarate/lamivudine, were recruited. Ectocervical biopsies were obtained for quantification of TFVdp and 3TCtp using liquid chromatography-mass spectrometry. 16S rRNA gene sequencing was performed on DNA extracted from vaginal swabs. Wilcoxon rank sum was used to test for differences between contraceptive groups. RESULTS: 3TCtp concentrations were on average 17-fold greater than TFVdp concentrations in cervical tissues. TFVdp concentrations in cervical biopsies were 76% greater in DMPA users compared to women using non-hormonal contraception (n=23/group). Abundance of Lactobacillus in vaginal swabs was correlated with 3TCtp concentrations in cervical tissues. DISCUSSION: We found that TFVdp concentrations were significantly greater in DMPA-users compared to women using non-hormonal contraception, suggesting prevention efficacy is unlikely to be compromised by DMPA use. Similar to reports of FTCtp, 3TCtp exposure was significantly greater than TFVdp in cervical tissue and was correlated with abundance of Lactobacillus. These data support lamivudine as an option for pre-exposure prophyalxis.

13.
Antivir Ther ; 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31085814

RESUMO

BACKGROUND: Vitamin D (VitD) and calcium (Ca) supplementation attenuates antiretroviral therapy (ART)-associated bone loss, but it is unclear whether this effect is mediated through immunomodulation. METHODS: In this exploratory analysis of A5280, a 48-week, randomized, double-blind, placebo-controlled study of VitD/Ca supplementation with ART initiation, we characterized lymphocyte phenotypes and receptor activator of nuclear factor kappa-B ligand (RANKL) expression by median fluorescence intensity (MFI) at baseline and 48 weeks. Changes were evaluated within and between treatment groups by Wilcoxon signed rank and rank sum tests, respectively. Spearman correlations estimated relationships between cellular phenotypes and bone mineral density (BMD). RESULTS: Of 165 participants enrolled, 138 had samples for cellular phenotypes (64 VitD/Ca, 74 placebo). Markers of CD4, CD8 activation (CD38+HLA-DR+) declined (all P<0.001), but did not differ between arms. There was no decline in either %T-cells (CD4 and CD8) expressing RANKL or expression of RANKL by MFI. CD4 and CD8 activation markers were not correlated with BMD at baseline (r<0.15 and P>0.09 for all), but greater declines in CD4 activation correlated with greater declines in hip and spine BMD in both arms (0.25 ≤r ≤0.37, all P<0.05). A greater decline in CD8 activation was correlated with greater declines in both hip and spine BMD in the placebo arm only (hip r=0.31, P=0.009; spine r=0.25, P=0.035). CONCLUSIONS: Reductions in T-cell activation are characteristic of ART initiation, but only correlated modestly with bone loss. VitD/Ca supplementation does not appear to mitigate bone loss through modulation of immune activation or expression of RANKL. TRIAL REGISTRATION NUMBER: NCT01403051.

14.
J Acquir Immune Defic Syndr ; 81(2): e49-e54, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939531

RESUMO

OBJECTIVE: To examine associations between plasma cystatin C and neurocognitive impairment (NCI) and its performance as a diagnostic marker before and during initial antiretroviral therapy (ART). METHODS: Multivariable logistic regression and generalized estimating equations examined associations with NCI, determined by neuropsychological measurements, in participants of a 48-week randomized clinical trial of initial ART. Receiver operator characteristic curves examined diagnostic models of NCI. RESULTS: Cystatin C was associated with NCI before ART [odds ratio (OR) 3.4 (95% CI: 1.2 to 9.4) for each 2-fold increase in baseline levels] and during 48 weeks of ART, in models that excluded baseline measurements [OR 3.0 (1.2 to 7.8) for each 2-fold increase in time-updated levels]. The strength of association increased with more severe impairment using HIV-associated neurocognitive disorder criteria [OR 2.2 (0.8 to 6.0) with asymptomatic NCI and OR 4.0 (1.5 to 11.0) with mild neurocognitive disorder or HIV-associated dementia vs. no impairment, for each 2-fold increase in time-updated levels] or by global development score [OR 2.6 (1.1 to 6.3) with mild impairment and OR 4.6 (1.1 to 18.9) with moderate or severe impairment vs. no impairment]. Cystatin C performed poorly as a diagnostic marker for NCI, however, with an area under the receiver operator characteristic curve of 0.58 at baseline and 0.54 at week 48. CONCLUSIONS: Higher plasma cystatin C levels were significantly associated with NCI, but these levels did not seem to be useful as a diagnostic marker for this condition.

15.
Antivir Ther ; 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31032811

RESUMO

BACKGROUND: The long-term trajectory of and factors affecting lean mass in people living with HIV (PLWH) are incompletely described. METHODS: PLWH in the Modena HIV Metabolic Cohort underwent dual-energy X-ray absorptiometry (DXA) scans every 6-12 months for up to 10 years (median 4.6 scans). Mixed effect regression modelling in combined and sex-stratified models determined annual rates of and clinical factors significantly associated with appendicular lean mass (ALM). RESULTS: A total of 839 women and 1,759 men contributing ≥2 DXA scans had baseline median age 44 years and 14 years since HIV diagnosis; 76% were virologically suppressed on antiretroviral therapy (ART). Baseline median ALM was 16.9 kg for women and 24.8 kg for men. ALM decreased during the study period, with mean yearly ALM loss of -231 g in women and -322 g in men. Less ALM was associated with female sex, age >50 years, detectable HIV-1 RNA, and tenofovir and integrase inhibitor use. Greater ALM was associated with longer ART duration. In sex-stratified models, relationships between ALM and total ART duration and integrase inhibitor use were not significant for women, but the relationship with tenofovir use persisted. For men, AIDS wasting and CD4+ T-lymphocyte nadir <200 cells/µl were independently associated with lower ALM. CONCLUSIONS: ALM steadily declined over time in this cohort of PLWH on ART that included a large number of women. HIV- and ART-specific risk factors emerged that varied by sex. The observed associations between tenofovir or integrase inhibitor use and lower ALM particularly warrant further study.

16.
Obes Surg ; 29(8): 2503-2510, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30997619

RESUMO

OBJECTIVE: Bariatric surgery leads to more rapid and greater weight loss (WL) compared to medical weight loss (MWL), but the differences in body composition (BC) changes for these modalities remain unclear. Due to the known health risks associated with central adiposity, we compared the changes in regional distribution of fat mass (FM) and lean mass (LM) after surgical versus MWL. METHODS: In this 1:1:1 randomized trial among 15 persons with type 2 diabetes and body mass index (BMI) 30-39.9 kg/m2, we compared changes in BC, by dual-energy X-ray absorptiometry and abdominal computerized tomography, at time of 10%WL or 9 months after intervention (whichever came first). Participants underwent MWL, adjustable gastric banding (AGB), or Roux-en-Y gastric bypass (RYGB). Non-parametric tests evaluated BC differences (FM, LM, and visceral adipose tissue [VAT]) within and across all three arms and between pair-wise comparisons. RESULTS: Twelve female participants (75% African American) completed the study. Patient age, BMI, and baseline anthropometric characteristics were similar across study arms. AGB lost more LM (MWL - 5.2%, AGB - 10.3%, p = 0.021) and VAT (MWL + 10.9%, AGB - 28.0%, p = 0.049) than MWL. RYGB tended to lose more VAT (MWL +10.9%, RYGB - 20.2%, p = 0.077) than MWL. AGB tended to lose more LM than RYGB (AGB - 12.38%, RYGB - 7.29%, p = 0.15). CONCLUSIONS: At similar WL, AGB lost more LM and VAT than MWL; RYGB similarly lost more VAT. Given the metabolic benefits of reducing VAT and retaining LM, larger studies should confirm the changes in BC after surgical versus medical WL. CLINICAL TRIAL REGISTRATION: NCTDK089557 - ClinicalTrials.gov.

17.
J Acquir Immune Defic Syndr ; 81(3): e85-e91, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939529

RESUMO

BACKGROUND: Proteinuria has been associated with bone loss and fractures in general population, but data in HIV-infected population are lacking. SETTING: Prospective, multicenter cohort study of men with or at risk of HIV infection. METHODS: Between 2006 and 2015, urine protein measurements and bone fracture histories were ascertained semiannually in 947 HIV-infected (HIV+) and 969 HIV-uninfected (HIV-) men aged 40 years or older. Proteinuria was defined as protein-to-creatinine ratio ≥200 mg/g at ≥2 consecutive visits. Outcome measures (1) all fractures (excluding fractures of skull, face, and digits) and (2) fragility fractures (fractures of vertebral column, femur, wrist, and humerus). Multivariable Cox proportional hazards models assessed the association between proteinuria and fracture after adjusting for additional risk factors. RESULTS: The overall period prevalence of proteinuria was higher among HIV+ than HIV- (29% vs 6%, P < 0.001). Men with proteinuria had a significantly higher risk of fragility fracture compared with men without proteinuria [adjusted hazard ratio (aHR) = 2.29 (1.12-4.66)] and did not differ by HIV serostatus (p-interaction = 0.83). The risk of all fractures was not statistically different between men with or without proteinuria [aHR = 1.31 (0.84-2.05)]. Among HIV+ men, the association between confirmed proteinuria and fragility fracture was attenuated [aHR = 2.12 (0.95-4.73)] after additional adjustment for CD4 T-cell count/mm, history of AIDS, the presence of detectable plasma HIV-1 RNA, and cumulative exposure to tenofovir disoproxil fumarate. CONCLUSIONS: Proteinuria was more common in HIV+ than in HIV- men and was a strong independent risk factor for fragility fracture regardless of HIV serostatus. Proteinuria should prompt consideration of a thorough evaluation for bone disease among HIV+ persons.

18.
AIDS ; 33(6): 1053-1061, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30946159

RESUMO

OBJECTIVE: Whether HIV modifies the relationship of serum lipids with coronary atherosclerosis and coronary plaque subtypes is uncertain. We examined the associations between traditional lipids and coronary atherosclerosis among HIV-infected (HIV+) and HIV-uninfected (HIV-) men. DESIGN: The Multicenter AIDS Cohort Study is an observational cohort with a total of 429 HIV+ and 303 HIV- men who had non-contrast cardiac computed tomography performed to measure coronary artery calcium and coronary computed tomography angiography to measure coronary stenosis, coronary plaque presence, and composition. METHODS: We used multivariable adjusted prevalence ratios to examine the relationship between the SD difference in each lipid parameter and coronary atherosclerosis. RESULTS: Total cholesterol (TC)/HDL-cholesterol had the strongest associations with coronary atherosclerosis regardless of HIV status. Overall, lipid parameters were most strongly associated with the presence of mixed plaque, stenosis more than 50%, and coronary artery calcium for both HIV+ and HIV- men. HIV+ men had similar, but weaker associations, between lipid parameters and coronary atherosclerosis compared with HIV- men. The strongest association was between the TC/HDL-cholesterol and stenosis more than 50% for both HIV+ [prevalence ratios 1.25 per SD (95% confidence interval 1.07-1.43)] and HIV- men [prevalence ratios 1.46 per SD (95% confidence interval 1.08-1.85)]. CONCLUSION: The associations between lipids and coronary atherosclerosis tended to be weaker for HIV+ compared with HIV- men, although TC/HDL had the strongest association for both HIV+ and HIV- men. A weaker association between lipid levels and coronary atherosclerosis for HIV+ men may contribute to the decreased discrimination of cardiovascular disease risk observed in HIV+ individuals.

19.
J Allergy Clin Immunol Pract ; 7(6): 1868-1873.e5, 2019 Jul - Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30857941

RESUMO

BACKGROUND: Metabolic dysfunction may contribute to worsened asthma in obesity. The relationship between prediabetes and diabetes, metabolic conditions more common in obesity, and asthma outcomes is not well characterized. OBJECTIVE: We sought to determine the association between prediabetes/diabetes and asthma exacerbations in an obese asthma cohort. METHODS: A retrospective cohort of US obese adults with asthma, aged 18-64, was created from a claims-based health services database spanning 2010 to 2015. Individuals with a hemoglobin A1c (HbA1c) measurement were identified, categorized as within normal (<5.6%), prediabetes (5.7% to 6.4%), and diabetes (≥6.5%) ranges. Exacerbations, defined as asthma-related hospitalization, emergency department visit, or corticosteroid prescription ±14 days of an asthma-related outpatient visit, were ascertained. Associations were fit with zero-inflated negative binomial models, adjusted for age, sex, region, smoking, medication use, and comorbidities. RESULTS: A total of 5722 individuals were identified. Higher HgbA1c was associated with higher asthma exacerbation rates. In the fully adjusted model, compared with individuals with normal HbA1c, those in the prediabetes range had a 27% higher rate (95% confidence interval [CI], 5% to 52%), and those in the diabetes range had a 33% higher rate (95% CI, 2% to 73%). CONCLUSIONS: Prediabetes and diabetes were associated with higher rates of asthma exacerbation among obese adults with asthma. Results support evidence that insulin resistance and metabolic syndrome, metabolic features common in prediabetes/diabetes, can influence asthma morbidity.

20.
J Antimicrob Chemother ; 74(5): 1381-1388, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30768163

RESUMO

BACKGROUND: The mechanisms behind ART-induced bone changes in HIV-infected patients are poorly known. We aimed to analyse changes in inflammatory and bone markers in HIV after tenofovir disoproxil fumarate initiation, and the associations with changes in the bone strength parameters. METHODS: HIV-positive participants starting tenofovir disoproxil fumarate-based ART underwent dual-energy X-ray absorptiometry (QDR 4500 SL®, Hologic, Waltham, MA, USA) for bone mineral density (BMD), a microindentation test (OsteoProbe®, Active Life Scientific, Santa Barbara, CA, USA) for bone quality [bone material strength index (BMSi)] and phlebotomy at baseline and 48 weeks after ART. A panel of inflammatory biomarkers and bone turnover markers were measured by ELISA. HIV-negative controls underwent identical procedures once. Values are expressed as medians and IQRs, and non-parametric tests were used to perform the analysis. RESULTS: Twenty HIV-infected individuals and 20 HIV-negative control individuals were matched in terms of age and gender. HIV individuals showed higher levels of inflammatory markers. We found no differences in bone turnover markers. HIV-positive individuals presented lower BMSi values at baseline compared with controls [86 (83-90) versus 89 (88-93), respectively; P = 0.034]. We found no difference in BMD (at either of the sites evaluated). BMSi tended to increase with treatment. IL-1ß at baseline was positively correlated with changes in BMSi after ART (rho = 0.564, P = 0.014). Baseline levels of sclerostin tended to be negatively correlated with changes in BMSi (rho = -0.402, P = 0.097). We found a negative correlation between time since HIV diagnosis and changes in BMSi (rho = -0.466, P = 0.04). CONCLUSIONS: We observed a correlation between changes in bone quality and the inflammatory environment in HIV-positive individuals. Moreover, among the underlying mechanisms we highlight the Wnt pathway as having a potentially significant role in ART bone quality recovery.

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