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BACKGROUND We have previously shown that the initiation of antiretroviral therapy (ART) is associated with a decrease in skeletal muscle density (greater fat accumulation), suggesting that gains in lean body mass seen in many ART studies may reflect gains in low quality, fatty muscle. Here, we explore whether skeletal muscle density and area are associated with markers of inflammation and immune activation. METHODS ART-naive people with HIV were randomized to raltegravir or ritonavir-boosted atazanavir or darunavir, each with tenofovir disoproxil fumarate/emtricitabine. Abdominal computed tomography scans from baseline and week 96 were reanalyzed for psoas density and area and correlations explored with inflammation [interleukin-6 (IL-6) and high-sensitivity C-reactive protein] and immune activation [soluble CD14 (sCD14), soluble CD163 (sCD163), and %CD38+HLADR+ on CD4+ or CD8+ T cells]. RESULTS Two hundred twenty-two participants had available inflammation/immune activation markers and paired computed tomography scans. At baseline, lower psoas density (greater fat) correlated with higher IL-6 (r = -0.26, P < 0.001) and sCD163 (r -0.15, P = 0.03) and lower lean psoas area correlated with higher IL-6, high-sensitivity C-reactive protein, sCD14, sCD163, and %CD38+HLADR+ on CD4+ T cells (r = -0.30-0.13; all P ≤ 0.05). From baseline to week 96, greater percent decrease in total psoas density (more fat) correlated with greater increase in IL-6 (r = -0.14; P = 0.04); greater % decrease in lean psoas area correlated greater increases in IL-6, sCD14, sCD163, and %CD38+HLADR+ on CD8+ T cells (r = -0.15 to -0.18; all P < 0.04). CONCLUSIONS Greater fat infiltration within the psoas muscle (lower density) and greater loss in lean psoas muscle area were associated with higher inflammation and immune activation, which may portend important effects on muscle function and cardiometabolic risk.

DEAP-3600 is a liquid-argon scintillation detector looking for dark matter. Scintillation events in the liquid argon (LAr) are registered by 255 photomultiplier tubes (PMTs), and pulseshape discrimination (PSD) is used to suppress electromagnetic background events. The excellent PSD performance of LAr makes it a viable target for dark matter searches, and the LAr scintillation pulseshape discussed here is the basis of PSD. The observed pulseshape is a combination of LAr scintillation physics with detector effects. We present a model for the pulseshape of electromagnetic background events in the energy region of interest for dark matter searches. The model is composed of (a) LAr scintillation physics, including the so-called intermediate component, (b) the time response of the TPB wavelength shifter, including delayed TPB emission at $${\mathcal {O}}$$O(ms) time-scales, and c) PMT response. TPB is the wavelength shifter of choice in most LAr detectors. We find that approximately 10% of the intensity of the wavelength-shifted light is in a long-lived state of TPB. This causes light from an event to spill into subsequent events to an extent not usually accounted for in the design and data analysis of LAr-based detectors.

Introduction The predictive potential of demographics, clinical characteristics, and inflammatory markers at admission to determine future intubation needs of hospitalised CoVID-19 patients is unknown. The study aimed to determine the predictive potential of elevated serum inflammatory markers in determining the need for intubation in CoVID-19 Patients. Methods In a retrospective cohort study of hospitalised SARS-CoV2 positive patients, single and multivariable regression analyses were used to determine covariate effects on intubation odds, and a minimax concave penalty regularised logistic regression was used to build a predictive model. A second prospective independent cohort tested the model. Results Systemic inflammatory markers obtained at admission were higher in patients that required subsequent intubation, and adjusted odds of intubation increased for every standard deviation above the mean for c-reactive protein (CRP) OR:2.8 (95% CI 1.8-4.5, p Conclusion In patients hospitalised with CoVID-19, elevated serum inflammatory markers measured within the first twenty-four hours of admission are associated with an increased need for intubation. Additionally, a model of C-reactive protein, lactate dehydrogenase, and the presence of diabetes may play a predictive role in determining the future need for intubation.

Obesity is becoming increasingly prevalent in paediatric populations worldwide. In addition to increasing prevalence, the severity of obesity is also continuing to rise. Taken together, these findings demonstrate a worrying trend and highlight one of the most significant challenges to public health. Childhood obesity affects multiple organs in the body and is associated with both significant morbidity and ultimately premature mortality. The prevalence of complications associated with obesity, including dyslipidaemia, hypertension, fatty liver disease and psychosocial complications are becoming increasingly prevalent within the paediatric populations. Treatment guidelines currently focus on intervention with lifestyle and behavioural modifications, with pharmacotherapy and surgery reserved for patients who are refractory to such treatment. Research into adult obesity has established pharmacological novel therapies, which have been approved and established in clinical practice; however, the research and implementation of such therapies in paediatric populations have been lagging behind. Despite the relative lack of widespread research in comparison to the adult population, newer therapies are being trialled, which should allow a greater availability of treatment options for childhood obesity in the future. This review summarizes the current evidence for the management of obesity in terms of medical and surgical options. Both future therapeutic agents and those which cause weight loss but have an alternative indication are also included and discussed as part of the review. The review summarizes the most recent research for each intervention and demonstrates the potential efficacy and limitations of each treatment option.

Older Black adults face a disproportionate burden of HIV prevalence, but less is known about racial disparities in age-related outcomes in HIV. We assessed the effect of HIV status and race on motor and pulmonary function, as well as how they contribute to mobility disability. Community-based study; Chicago, IL Participants were 363 community-dwelling adults age ≥ 50 years, 48% living with HIV, and 68% Black. Participants with HIV were recruited from a specialty HIV clinic, and participants without HIV (comparable on key demographic, lifestyle, and behavioral characteristics) were recruited from the community. Measures included motor function summarized by 10 motor performance measures, pulmonary function summarized by 3 measures assessed using handheld spirometry, and self-reported mobility disability. In fully adjusted linear models, HIV was associated with better motor (β = 9.35, p

Background We sought to identify factors associated with weight gain in randomized clinical trials of antiretroviral therapy (ART) switch. Methods We explored the effects of demographic factors, clinical characteristics, and ART on weight gain in a pooled analysis of 12 prospective clinical trials, wherein virologically suppressed people living with human immunodeficiency virus (PWH) were randomized to switch or remain on a stable baseline regimen (SBR). Results Both PWH randomized to switch ART (n = 4166) and those remaining on SBR (n = 3150) gained weight. Median weight gain was greater in those who switched (1.6 kg, interquartile range [IQR], –.05 to 4.0 vs 0.4 kg, [IQR], –1.8 to 2.4 at 48 weeks, P Conclusions Moderate weight gain after ART switch was common and usually plateaued by 48 weeks. Baseline ART was a predictor of post-switch weight gain; participants who switched off of EFV and TDF had the greatest weight gain. The biological mechanisms that underlie the differential effects of switching ART agents on weight and associated clinical implications require further study.

Objectives Childhood obesity is a public health concern worldwide, with rates continuing to rise, despite preventive measures. Lifestyle modification remains the mainstay in the treatment of patients with excessive weight, but unfortunately, this is not always successful. Options for medical management of obesity in the paediatric population are limited. Methods Seven adolescents (all girls, mean age 14.9 years) with a body mass index (BMI) above 98th percentile and serious complications secondary to obesity were offered an intense weight management programme. The participants were reviewed by a multidisciplinary team every two weeks for advice and support, and treated with daily subcutaneous injections of liraglutide (dose range 1.2–3.0 mg). Scores for anxiety and depression were evaluated using the Revised Child Anxiety and Depression Scale. Results The results showed a significant weight loss over the three months with an average reduction of 5.4 kg (4.2%; 95% CI 1.93–8.78; p=0.0087). The mean drop in BMI was 2.1 kg/m2, which is statistically significant (95% CI 0.973–3.199; p=0.0037). Resolution of complications (raised intracranial pressure and steatohepatitis) was noted following weight loss. Anxiety and depressive symptoms improved over the three-month intervention course, especially features of separation anxiety disorder. Liraglutide was well tolerated by all patients. Conclusions Liraglutide medication, alongside a dedicated multidisciplinary team guided lifestyle therapy, is effective and safe in the treatment for excessive weight in adolescents, leading to the reversal of the complications related to obesity and improvement in the psychological symptoms.

BACKGROUND The longer-term risks of statins on physical function among people with HIV are unclear. METHODS Longitudinal analysis of Multicenter AIDS Cohort Study men between 40 and 75 years of age with ≥2 measures of gait speed or grip strength. Generalized estimating equations with interaction terms between (1) statin use and age and (2) HIV serostatus, age, and statin use were considered to evaluate associations between statin use and physical function. Models were adjusted for demographics and cardiovascular risk factors. RESULTS Among 2021 men (1048 with HIV), baseline median age was 52 (interquartile range 46-58) years; 636 were consistent, 398 intermittent, and 987 never statin users. There was a significant interaction between age, statin, and HIV serostatus for gait speed. Among people with HIV, for every 5-year age increase, gait speed (m/s) decline was marginally greater among consistent versus never statin users {-0.008 [95% confidence interval (CI) -0.017 to -0.00007]; P = 0.048}, with more notable differences between intermittent and never users [-0.017 (95% CI -0.027 to -0.008); P < 0.001]. Similar results were observed among men without HIV. Significant differences in grip strength (kg) decline were seen between intermittent and never users [-0.53 (95% CI -0.98 to -0.07); P = 0.024] and differences between consistent and never users [-0.28 (95% CI -0.63 to 0.06); P = 0.11] were not statistically significant. CONCLUSIONS Among men with and without HIV, intermittent statin users had more pronounced declines in physical function compared with consistent and never users. Consistent statin use does not seem to have a major impact on physical function in men with or without HIV.

OBJECTIVES Fat quality and quantity may affect health similarly or differently. Fat quality can be assessed by measuring fat density on CT scan (greater density = smaller, higher quality adipocytes). We assessed the effects of tesamorelin, a growth hormone-releasing hormone analogue that reduces visceral fat (VAT) quantity in some people living with HIV (PWH), on fat density. DESIGN Participants from two completed, placebo-controlled, randomized trials of tesamorelin for central adiposity treatment in PWH were included if they had either a clinical response to tesamorelin (VAT decrease ≥8%, ≈70% of participants) or were placebo-treated. METHODS CT VAT and subcutaneous fat (SAT) density (Hounsfield Units, HU) were measured by a central blinded reader. RESULTS Participants (193 responders, 148 placebo) were 87% male and 83% white. Baseline characteristics were similar across arms, including VAT (-91 HU both arms, P = 0.80) and SAT density (-94 HU tesamorelin, -95 HU placebo, P = 0.29). Over 26 weeks, mean (SD) VAT and SAT density increased in tesamorelin-treated participants only [VAT: +6.2 (8.7) HU tesamorelin, +0.3 (4.2) HU placebo, P

While a great deal of literature has been published in recent years on infections in kidney transplant (KT) recipients, there is a relative paucity of literature on infections and their impact on the graft and overall health of older KT recipients. We reviewed the most recent literature and guidelines in the field of kidney transplantation and summarized the current recommendations for physicians caring for older KT recipients at risk for infections. Older KT recipients are at an increased risk of infections during the first year post-KT resulting in readmission or other poor outcomes, compared to younger KT recipients. Immune senescence and frailty likely increase the risk for infections in older KT recipients during the first year post-KT when KT recipients are receiving a higher degree of immune suppressive therapy. Most common infections include urinary tract infections, bloodstream infections, cytomegalovirus reactivation or primary infection, and BK virus. A majority of older KT recipients survive and have a functioning graft at 1 year. KT can be a successful treatment for older adults on dialysis if post-transplant complications, including rejection and infection, can be appropriately managed. Despite this increased risk for infections, older KT recipients have a lower risk for all-cause mortality and death secondary to infections compared with patients on dialysis. Further studies on modification of immune suppression and prophylactic strategies are much needed in this high-risk KT population.

Background Muscle mitochondrial dysfunction associated with HIV and antiretroviral therapy (ART) may improve with exercise. Methods Muscle specimens obtained before and after 24 weeks of exercise in older people with HIV (PWH; n = 18; ART >2 years) and uninfected controls (n = 21) were analyzed for citrate synthase (CS) activity and complexes (C) I–V, manganese superoxide dismutase (MnSOD), peroxisome proliferator-activated receptor-γ coactivator-1 (PGC1α), and voltage-dependent anion channel 1 (VDAC1) content. Results Only controls had increased CS, MnSOD, PGC1α, and CIV (P ≤ .01; P < .01 vs PWH) after training. Conclusions The blunted mitochondrial adaptations to training in PWH suggests the need for different types of exercise-induced stimulation. Clinical Trials Registration NCT02404792.

BACKGROUND/OBJECTIVE The current approach to measuring ventilatory (in)efficiency (V'E -V'CO2 slope, nadir and intercept) presents critical drawbacks in the evaluation of COPD subjects, owing mainly to mechanical ventilatory constraints. Thus, we aimed to compare the current approach with a new method we have developed for ventilatory efficiency calculation. METHODS The new procedure was based on measuring the amount of CO2 cleared by the lungs (V'CO2 , L/min) plotted against a predefined range of increase in minute ventilation (V'E ) (ten-fold increase based on semilog scale) during incremental exercise to symptom-limited maximum tolerance. This value was compared to a hypothetical predicted maximum CO2 output at the predicted maximal voluntary ventilation, defining ventilatory efficiency (ηV'E , %). The results were used to compare 30 subjects with COPD (II-IV Global Initiative for Chronic Obstructive Lung Disease, GOLD) and 10 non-COPD smokers, to establish the best discriminative physiological variable for disease severity through logistic multinomial regression. RESULTS The new approach was more sensitive to progressive deterioration of airway obstruction, resulting in worse ηV'E as lung function worsens throughout the GOLD panel (ηV'E (%), p

The accumulation of INTERmuscular fat and INTRAmuscular fat (IMF) has been a hallmark of individuals with diabetes, those with mobility impairments such as spinal cord injuries and is known to increase with aging. An elevated amount of IMF has been associated with fractures and frailty, but the imprecision of IMF measurement has so far limited the ability to observe more consistent clinical associations. Magnetic resonance imaging has been recognized as the gold standard for portraying these features, yet reliable methods for quantifying IMF on magnetic resonance imaging is far from standardized. Previous investigators used manual segmentation guided by histogram-based region-growing, but these techniques are subjective and have not demonstrated reliability. Others applied fuzzy classification, machine learning, and atlas-based segmentation methods, but each is limited by the complexity of implementation or by the need for a learning set, which must be established each time a new disease cohort is examined. In this paper, a simple convergent iterative threshold-optimizing algorithm was explored. The goal of the algorithm is to enable IMF quantification from plain fast spin echo (FSE) T1-weighted MR images or from water-saturated images. The algorithm can be programmed into Matlab easily, and is semiautomated, thus minimizing the subjectivity of threshold-selection. In 110 participants from 3 cohort studies, IMF area measurement demonstrated a high degree of reproducibility with errors well within the 5% benchmark for intraobserver, interobserver, and test–retest analyses; in contrast to manual segmentation which already yielded over 20% error for intraobserver analysis. This algorithm showed validity against manual segmentations (r > 0.85). The simplicity of this technique lends itself to be applied to fast spin echo images commonly ordered as part of standard of care and does not require more advanced fat-water separated images.

Background People with human immunodeficiency virus (PWH) are at risk for accelerated development of physical function impairment and frailty; both associated with increased risk of falls, hospitalizations, and death. Identifying factors associated with physical function impairment and frailty can help target interventions. Methods The REPRIEVE trial enrolled participants 40–75 years of age, receiving stable antiretroviral therapy with CD4+ T-cell count >100 cells/mm3, and with low to moderate cardiovascular disease risk. We conducted a cross-sectional analysis of those concurrently enrolled in the ancillary study PREPARE at enrollment. Results Among the 266 participants, the median age was 51 years; 81% were male, and 45% were black, and 28% had hypertension. Body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) was 25 to Conclusions Physical function impairment was common among middle-aged PWH; greater BMI and physical inactivity are important modifiable factors that may prevent further decline in physical function with aging. Clinical Trials Registration NCT02344290.

People living with HIV (PLHIV) experience greater loss of muscle mass and function than people without HIV. However, HIV is not routinely recognized as a sarcopenia risk factor outside of HIV literature. The purposes of this study were to establish the prevalence and predictors of sarcopenia among PLHIV, and to compare the prevalence of sarcopenia among PLHIV and people without HIV. A systematic literature search of the PubMed, Embase, Cinahl, and Scielo databases was performed following PRISMA and MOOSE guidelines. Identified articles were included if they evaluated sarcopenia among PLHIV using either the presence of low muscle mass only or low muscle mass in association with low muscle function. The pooled prevalence of sarcopenia among PLHIV and the odds ratio for sarcopenia in PLHIV compared with controls were calculated. From 13 studies and 2267 participants, the prevalence of sarcopenia among PLHIV was 24.1% (95% CI = 17.8–31.0%). PLHIV presented 6.1 greater odds (95% CI = 1.1–33.5) of sarcopenia compared with people without HIV, matched by age, sex, BMI, and ethnicity. Longer exposure to specific HIV drugs, tobacco and alcohol, lower education and employment rates, and greater HIV duration were associated with sarcopenia. In conclusion, PLHIV had a high prevalence of sarcopenia, related to both HIV and non-HIV risk factors. HIV should be considered a risk factor for sarcopenia in the general population. CRD42019131449.

The bioacoustic method is an important tool for the identification of the ingestive behavior of ruminants, especially in extensive production systems. This is mainly due to its potential to solve the deficiencies presented by the usual method, which is based on the visual observation of the animals. In this article, we present a study whose main objective is to evaluate the accuracy of the bioacoustic method over the visual method to record the macroactivity of grazing cattle ingestive behavior. The comparison of the methods is made in terms of a multivariate statistical approach based on the use of Hotelling’s T2 test. To verify the test performance in comparing the methods, we developed a simulation study using a resampling approach. The results show that the bioacoustic method can be an effective alternative to the visual method, with the advantage of being a noninvasive method that also allows the analysis of the micro events of ingestive behavior.

Objective Limited studies have examined effects of bioaerosols on the respiratory health of dairy workers; previous findings have been inconsistent across populations. Methods Using a repeated measures design, exposures to dust, bioaerosols, and ozone were assessed and pre- and post-shift spirometry was performed for dairy workers (n = 36). Workers completed 1 to 8 visits. Linear mixed effect models estimated associations between air pollutant constituents and changes in spirometry. Results There was an association between higher dust exposures and increased peak expiratory flow rate. However, for all other outcomes there was no association with the exposures considered. Conclusions Relationships between bioaerosol exposures and respiratory health in dairy workers remain unclear. Future studies should increase sample sizes, include repeated measures designs, vary the timing of spirometry measurements, and include markers for Gram positive bacteria such as muramic acid or peptidoglycan.

Living with HIV has been proposed as a risk factor for the early development of functional decline. Composite marker tools like the Veterans Aging Cohort Study (VACS) Index, which includes HIV-associated and non-HIV-related markers of disease may better reflect multiorgan system injury and potentially predict functional outcomes. Therefore, the objective of this work is to determine whether higher VACS 2.0 Index scores predicts functional decline among older adults living with HIV (OALWH). Longitudinal study, including 131 adults ages 50 or older who underwent a comprehensive geriatric assessment at baseline and follow-up, at least a year apart. Functional status was determined by the gait speed (seconds for a 4-m distance). Linear regression models were constructed to determine the relationship between VACS 2.0 Index at baseline with gait speed at follow-up adjusted for potential confounders. The median for age was 58.0 years (range 50-84), and 81.7% were male. At baseline, the median VACS 2.0 Index score was 50.4 (interquartile range 42.2-65.3). The adjusted linear regression analysis found that higher baseline VACS 2.0 Index scores were significantly associated with a decline in gait speed (

The number of people with HIV (PWH) aged 50 years or older continues to steadily increase. The convergence of age- and HIV-related complications in these individuals presents a challenge for both patients and clinicians alike. New findings continue to emerge, as numerous researchers evaluate the combined impact of these two factors on quality of life, physiological systems, and mental health in PWH. Since its first occurrence in 2009, the International Workshop on HIV and Aging has served as a multidisciplinary meeting to share basic biomedical data, clinical trial results, treatment strategies, and epidemiological recommendations, toward better understanding and outcomes among like-minded scientific professionals. In this article, we share a selection of key findings presented in plenary talks at the 11th Annual International Workshop on HIV and Aging, held virtually from September 30, 2020 to October 2, 2020. We will also address the future directions of HIV and aging research, to further assess how the aging process intersects with chronic HIV.

A multiple linear regression analysis was performed on 12 independent variable predictors to determine the possible case fatality rates at the state level F, male to female ratio;COPD, congestive obstructive pulmonary disease;CVD, cardiovascular disease;DM, diabetes mellitus;HTN, hypertension;BMI, body mass index *No Hawaiian or Pacific Islander minority groups reported &No Hawaiian, Pacific Islander, or Native American minority groups reported

Background Treatment initiation with integrase strand transfer inhibitors (INSTIs) has been associated with excess weight gain. Whether similar gains are seen after switch to INSTIs among virologically suppressed persons is less clear. We assessed pre/post-INSTI weight changes from AIDS Clinical Trials Group participants (A5001 and A5322). Methods Participants who were in follow-up from 1997–2017 and switched to INSTI-based antiretroviral regimens were included. Piecewise linear mixed-effects models adjusting for age, sex, race/ethnicity, baseline BMI, nadir and current CD4+ T-cell count, smoking, diabetes and follow-up time with suppressed HIV-1 RNA examined weight and waist circumference change before and after first switch to INSTIs. Linear spline models with a single knot at time of switch accounted for nonlinear trends. Results The 972 participants who switched to INSTIs were 81% male and 50% nonwhite with a median age at switch of 50 years, CD4+ T-cell count 512 cells/μL, and BMI 26.4 kg/m2. Restricting to persons with suppressed HIV-1 RNA at switch (n = 691), women, blacks, and persons ≥60 years experienced greater weight gain in the 2 years after versus before switch. In adjusted models, white or black race, age ≥60, and BMI ≥30 kg/m2 at switch were associated with greater weight gain following switch among women; age ≥60 was the greatest risk factor among men. Trends for waist circumference were similar. Conclusions Yearly weight gain increased following switch to INSTIs, particularly for women, blacks, and persons aged ≥60. Concomitant increases in waist circumference suggest that this weight gain is associated with an increase in fat mass.

In this article, we use data from ethnography-inspired studies of eight Swedish schools. We describe and analyse how a number of neoliberal-inspired economic and political processes have (re)organi...

Objectives Adipose tissue (AT) density measurement may provide information about AT quality among people living with HIV. We assessed AT density and evaluated relationships between AT density and immunometabolic biomarker concentrations in men with HIV. Design Cross-sectional analysis of men enrolled in the Multicenter AIDS Cohort Study. Methods Abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density (Hounsfield units, HU; less negative = more dense) were quantified from computed tomography (CT) scans. Multivariate linear regression models described relationships between abdominal AT density and circulating biomarker concentrations. Results HIV+ men had denser SAT (−95 vs −98 HU HIV−, P s.d. greater SAT or VAT density was associated with higher levels of adiponectin, leptin, HOMA-IR and triglyceride:HDL cholesterol ratio and lower hs-CRP concentrations in HIV− men. Conversely, in HIV+ men, each s.d. greater SAT density was not associated with metabolic parameter improvements and was significantly (P s.d. greater VAT density were also observed among HIV+ men. Conclusions Among men living with HIV, greater SAT density was associated with greater systemic inflammation independent of SAT area. AT density measurement provides additional insight into AT density beyond measurement of AT quantity alone, and may have implications for metabolic disease risk.

Health care for older adults with human immunodeficiency virus can be highly complex, resource intensive, and carry a high administrative burden. Data from aging longitudinal cohorts and feedback from the human immunodeficiency virus community suggest that the current model is not meeting the needs of these older adults. We introduce the 6 Ms approach, which acknowledges the multicomplexity of older adults with human immunodeficiency virus, simplifies geriatric principles for non–geriatrics-trained providers, and minimizes extensive training and specialized screening tests or tools. Implementing novel approaches to care requires support at local/national levels.

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 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.

Background Neurocognitive impairment (NCI) is associated with monocyte activation in people with HIV (PWH). Activated monocytes increase glycolysis, reduce oxidative phosphorylation, and accumulate citrate and succinate, tricarboxylic acid (TCA) cycle metabolites that promote inflammation—this metabolic shift may contribute to NCI and slowed gait speed in PWH. Methods Plasma citrate and succinate were assayed by liquid chromatography–mass spectrometry from 957 participants upon entry to a multicenter, prospective cohort of older PWH. Logistic, linear, and mixed-effects linear regression models were used to examine associations between entry/baseline TCA cycle metabolites and cross-sectional and longitudinal NCI, neuropsychological test scores (NPZ-4), and gait speed. Results Median age was 51 (range 40–78) years. Each 1 standard deviation (SD) citrate increment was associated with 1.18 higher odds of prevalent NCI at baseline (P = .03), 0.07 SD lower time-updated NPZ-4 score (P = .01), and 0.02 m/s slower time-updated gait speed (P < .0001). Age accentuated these effects. In the oldest age-quartile, higher citrate was associated with 1.64 higher odds of prevalent NCI, 0.17 SD lower NPZ-4, and 0.04 m/s slower gait speed (P ≤ .01 for each). Similar associations were apparent with succinate in the oldest age-quintile, but not with gait speed. In participants without NCI at entry, higher citrate predicted a faster rate of neurocognitive decline. Conclusions Higher plasma citrate and succinate are associated with worse cross-sectional and longitudinal measures of neurocognitive function and gait speed that are age-dependent, supporting the importance of altered bioenergetic metabolism in the pathogenesis of NCI in older PWH.

Impairments in physical function and increased systemic levels of inflammation have been observed in middle-aged and older persons with HIV (PWH). We previously demonstrated that in older persons, associations between gut microbiota and inflammation differed by HIV serostatus. To determine whether relationships between the gut microbiome and physical function measurements would also be distinct between older persons with and without HIV, we reanalyzed existing gut microbiome and short chain fatty acid (SCFA) data in conjunction with previously collected measurements of physical function and body composition from the same cohorts of older (51–74 years), nonfrail PWH receiving effective antiretroviral therapy (N = 14) and age-balanced uninfected controls (N = 22). Associations between relative abundance (RA) of the most abundant bacterial taxa or stool SCFA levels with physical function and body composition were tested using HIV-adjusted linear regression models. In older PWH, but not in controls, greater RA of Alistipes, Escherichia, Prevotella, Megasphaera, and Subdoligranulum were associated with reduced lower extremity muscle function, decreased lean mass, or lower Short Physical Performance Battery (SPPB) scores. Conversely, greater RA of Dorea, Coprococcus, and Phascolarctobacterium in older PWH were associated with better muscle function, lean mass, and SPPB scores. Higher levels of the SCFA butyrate associated with increased grip strength in both PWH and controls. Our findings indicate that in older PWH, both negative and positive associations exist between stool microbiota abundance and physical function. Different relationships were observed in older uninfected persons, suggesting features of a unique gut–physical function axis in PWH.

Background: Physiologic aging has been associated with gut dysbiosis. Although short exercise interventions have been linked to beneficial changes in gut microbiota in younger adults, limited data are available from older populations. We hypothesized that exercise would produce beneficial shifts in microbiota and short-chain fatty acid (SCFA) levels in older persons. Methods: Stool samples were collected before and at completion of a supervised 24-week cardiovascular and resistance exercise intervention among 50–75-year-old participants. SCFA levels were analyzed by gas chromatography and microbiome by 16S rRNA gene sequencing. Negative binomial regression models compared pre- and post-differences using false discovery rates for multiple comparison. Results: A total of 22 participants provided pre-intervention samples; 15 provided samples at study completion. At baseline, the majority of participants were men (95%), mean age 58.0 (8.8) years, mean body mass index 27.4 (6.4) kg/m2. After 24 weeks of exercise, at the genus level, exercise was associated with significant increases in Bifidobacterium (and other unidentified genera within Bifidobacteriaceae), Oscillospira, Anaerostipes, and decreased Prevotella and Oribacterium ( p Conclusion: Our pilot study suggested that an exercise intervention is associated with changes in the microbiome of older adults and a key bacterial metabolite, butyrate. Although some of these changes could potentially reverse age-related dysbiosis, future studies are required to determine the contribution of changes to the microbiome in the beneficial effect of exercise on overall health of older adults. Clinical Trials NCT02404792

The High-Intensity Exercise Study to Attenuate Limitations and Train Habits in Older Adults With HIV (HEALTH), which incorporates an exercise and biobehavioral coaching intervention, has the following overall goals: (a) to determine whether high-intensity interval training (HIIT) mitigates physical function impairments, fatigue, and impairments in mitochondrial bioenergetics of older people living with HIV (PLWH) to a greater extent than continuous moderate exercise (CME); and (b) to determine whether a biobehavioral coaching and mobile health text messaging intervention after HIIT or CME can promote long-term adherence to physical activity. The HEALTH study is a randomized trial of 100 older PLWH (≥50 years of age) who self-report fatigue and have a sedentary lifestyle. Enrolled participants will be randomized to 16 weeks of supervised HIIT or CME training, followed by a 12-week maintenance phase, involving a mobile health coaching intervention. Outcomes of the HEALTH study will inform the development of scalable, effective exercise recommendations tailored to the unique needs of aging PLWH.

One of the challenges in photovoltaic solar plants is the performance maintenance in the presence of adverse environmental conditions. Soiling on the solar panels is one of those challenges having a high decrease impact on the power generation. This work proposes a statistical methodology that estimates the energy losses due to soiling on photovoltaic solar plants. Using environmental and power generation data, the proposed methodology predicts the energy generation using a regression model; and then evaluates if the differences between the observed energy generation data and the predicted energy data are due to soiling. The experiments to validate the system are based on one-year dataset of environmental and power generation data from a solar plant located in the northeast region of Brazil. The results showed that the daily energy losses estimates ranged from 2.20% up to 12.31% in a period less than a month.

Background: Chronic inflammation contributes to aging and organ dysfunction in the general population, and is a particularly important determinant of morbidity and mortality among people with HIV (PWH). The effect of cannabis use on chronic inflammation is not well understood among PWH, who use cannabis more frequently than the general population. Materials and Methods: We evaluated participants in the Multicenter AIDS Cohort Study (MACS) beginning in 2004 with available data on cannabis use and inflammatory biomarkers. Associations of current cannabis use with plasma concentrations of inflammatory markers were adjusted for hepatitis C, tobacco smoking, and comorbidities. Markers were analyzed individually and in exploratory factor analysis (EFA). Results: We included 1352 men within the MACS. Twenty-seven percent of HIV-negative men, 41% of HIV viremic men, and 35% of virologically suppressed men reported cannabis use at baseline. Among cannabis users, 20-25% in all groups defined by HIV serostatus were daily users, and the same proportion reported weekly use. The remaining ∼50% of users in all groups reported monthly or less frequent use. Four biomarker groupings were identified by EFA: Factor 1: immune activation markers; Factor 2: proinflammatory cytokines; Factor 3: Th1- and Th2-promoting cytokines; and Factor 4: inflammatory chemokines. In EFA, daily users had 30% higher levels of Factor 2 biomarkers than nonusers (p=0.03); this was the only statistically significant difference by cannabis use status. Among individual markers, concentrations of IL-1β, IL-2, IL-6, and IL-8 (Factor 2); IL-10 (Factor 3); and BAFF (Factor 1) were higher (p

Purpose of review Older adults account for the majority of people with HIV (PWH) in high-income countries and have increasingly complex clinical profiles related to premature aging. Frailty is an important geriatric syndrome affecting a minority of PHW. Frailty negatively affects PHW's clinical status and quality of life. This review will update care providers on the current state of frailty that limits the healthspan of PWH. Recent findings Ongoing low-level HIV replication in treated PWH leads to immune activation and chronic inflammation contributing to the destabilization of normally autoregulated physiologic systems in response to environmental and biologic challenges characteristic of frailty. Understanding these underlying mechanisms will determine potential intervention options. Potentially reversible risk factors that promote progression to and reversion from the dynamic state of frailty are being studied and will help prevent frailty. Simple assessment tools and treatment strategies for frailty are being adapted for aging PWH. Summary Insight into underlying biologic mechanisms and adapting proven geriatric principles of interdisciplinary care will inform the healthy aging of PWH.

PURPOSE OF REVIEW: While the characteristics associated with frailty in people with HIV (PWH) have been well-described, little is known regarding interventions to slow or reverse frailty. Here we review interventions to prevent or treat frailty in the general population and in people with HIV (PWH). RECENT FINDINGS: Frailty interventions have primarily relied on non-pharmacologic interventions (e.g., exercise, nutrition). Although few have addressed frailty, many of these therapies have shown benefit on components of frailty including gait speed, strength, and low activity among PWH. When non-pharmacologic interventions are insufficient, pharmacologic interventions may be necessary. Many interventions have been tested in preclinical models, but few have been tested or shown benefit among older adults with or without HIV. SUMMARY: Ultimately, pharmacologic and non-pharmacologic interventions have the potential to improve vulnerability that underlies frailty in PWH, though clinical data is currently sparse.

RationalePrognostic tools for aiding in the treatment of hospitalized COVID-19 patients could help improve outcome by identifying patients at higher or lower risk of severe disease.ObjectivesThe study objective was to develop models to stratify patients by risk of severe outcomes during COVID-19 hospitalization using readily available information at hospital admission.MethodsHierarchical ensemble classification models were trained on a set of 229 patients hospitalized with COVID-19 to predict severe outcomes, including ICU admission, development of ARDS, or intubation, using easily attainable attributes including basic patient characteristics, vital signs at admission, and basic lab results collected at time of presentation. Each test stratifies patients into groups of increasing risk. An additional cohort of 330 patients was used for blinded, independent validation. Shapley value analysis evaluated which attributes contributed most to the models’ predictions of risk.Measurements and Main ResultsTest performance was assessed using precision (positive predictive value) and recall (sensitivity) of the final risk groups. All test cut-offs were fixed prior to blinded validation. In both development and validation, the tests achieved precision in the lowest risk groups near or above 0.9. The proportion of patients with severe outcomes significantly increased across increasing risk groups. While the importance of attributes varied by test and patient, CRP, LDH, and D-dimer were often found to be important in the assignment of risk label.ConclusionsRisk of severe outcomes for patients hospitalized with COVID-19 infection can be assessed using machine learning-based models based on attributes routinely collected at hospital admission.

In smokers without manifest airway obstruction, early emphysema and endothelial dysfunction has been related to minute-ventilation/carbon dioxide output ratio (V′E/V′CO2). Thus, smokers with reduced lung carbon monoxide diffusion capacity (DLco) have a heightened V′E/V′CO2 ratio. We hypothesized that ventilatory inefficiency could contribute to the suspicion of impaired diffusive capacity in the absence of significant airway obstruction. Thus, 15 smokers with impaired DLco were compared to 15 smokers with normal DLco. Accuracy through sensibility and specificity for V′E/V′CO2 slope and nadir was compared with a new index for ventilatory efficiency (ηV′E,%), to uncover early diffusive changes in smokers without COPD.

Background Neurocognitive impairment (NCI) and frailty are more prevalent among persons with human immunodeficiency virus (HIV, PWH) compared to those without HIV. Frailty and NCI often overlap with one another. Whether frailty precedes declines in neurocognitive function among PWH or vice versa has not been well established. Methods AIDS Clinical Trials Group (ACTG) A5322 is an observational cohort study of older PWH. Participants undergo annual assessments for NCI and frailty. ACTG A5322 participants who developed NCI as indexed by tests of impaired executive functioning and processing speed during the first 3 years were compared to persons who maintained normal cognitive function; those who demonstrated resolution of NCI were compared to those who had persistent NCI. Participants were similarly compared by frailty trajectory. We fit multinomial logistic regression models to assess associations between baseline covariates (including NCI) and frailty, and associations between baseline covariates (including frailty) and NCI. Results In total, 929 participants were included with a median age of 51 years (interquartile range [IQR] 46–56). At study entry, 16% had NCI, and 6% were frail. Over 3 years, 6% of participants developed NCI; 5% developed frailty. NCI was associated with development of frailty (odds ratio [OR] = 2.06; 95% confidence interval [CI] = .94, 4.48; P = .07). Further adjustment for confounding strengthened this association (OR = 2.79; 95% CI = 1.21, 6.43; P = .02). Baseline frailty however was not associated with NCI development. Conclusions NCI was associated with increased risk of frailty, but frailty was not associated with development of NCI. These findings suggest that the presence of NCI in PWH should prompt monitoring for the development of frailty and interventions to prevent frailty in this population.

Background Accurate, rapid, inexpensive biomarkers are needed to differentiate COVID-19 from bacterial pneumonia, allowing effective treatment and antibiotic stewardship. We hypothesized that the ratio of ferritin to procalcitonin (F/P) reflects greater viral activity and host response with COVID-19 pneumonia, while bacterial pneumonia would be associated with less cytolysis (lower ferritin) and more inflammation (higher procalcitonin), thus a lower F/P ratio. Methods We conducted a retrospective study of adult patients admitted to a single University hospital in the US through May 2020, during the COVID-19 pandemic. We compared F/P ratio of patients diagnosed with COVID-19 or bacterial pneumonia, excluding patients with COVID-19 and bacterial co-infections. In a logistic regression, we controlled for age, sex, body mass index (BMI), diabetes (DM), and hypertension (HTN). We used a receiver operating characteristic analysis to calculate the sensitivity and specificity of F/P values for the diagnosis of COVID-19 versus bacterial pneumonia. Results Of 218 patients with COVID-19 and 17 with bacterial pneumonia, COVID-19 patients were younger (56 vs 66 years, p=0.04), male (66% vs 24%, p=0.009), had higher BMI (31 vs 27 kg/m2, p=0.03), and similar rates of HTN (59% vs 45%, p=0.3) and DM (32% vs 18%, p=0.2). The median F/P ratio was significantly higher in patients with COVID-19 (3195 vs 860, p=0.0003, Figure 1). An F/P ratio cut-off of ≥ 1250 generated a sensitivity of 78% and a specificity of 59% to correctly classify a COVID-19 case (Figure 2). When adjusted for age, gender, BMI, DM, and HTN, a ratio ≥ of 1250 was associated with significantly greater odds of COVID-19 versus bacterial pneumonia (OR: 4.9, CI: 1.5, 16.1, p=0.009). Figure 1. Ferritin to Procalcitonin Ratios of patients with COVID-19 and patients with Bacterial Pneumonia (controls). Figure 2. Receiver Operating Characteristic Analysis of Ferritin to Procalcitonin Ratio Cut-off Values Predicting COVID-19 Diagnosis. Conclusion We observed an elevated F/P ratio in patients with COVID-19 compared to those with bacterial pneumonia. A F/P ratio ≥ 1250 provides a clinically relevant increase in pre-test probability of COVID-19. Prospective studies evaluating the discriminatory characteristics of F/P ratio in larger cohorts is warranted. Disclosures All Authors: No reported disclosures

ObjectivesTo investigate the effectiveness of hydroxychloroquine and dexamethasone on coronavirus disease (COVID-19) mortality using patient data outside of randomized trials.DesignPhenotypes derived from electronic health records were analyzed using the stability-controlled quasi-experiment (SCQE) to provide a range of possible causal effects of hydroxy-chloroquine and dexamethasone on COVID-19 mortality.Setting and participantsData from 2,007 COVID-19 positive patients hospitalized at a large university hospital system over the course of 200 days and not enrolled in randomized trials were analyzed using SCQE. For hyrdoxychloroquine, we examine a high-use cohort (n=766, days 1 to 43) and a later, low-use cohort (n=548, days 44 to 82). For dexamethasone, we examine a low-use cohort (n=614, days 44 to 101) and high-use cohort (n=622, days 102 to 200).Outcome measure14-day mortality, with a secondary outcome of 28-day mortality.ResultsHydroxycholoroquine could only have been significantly (pConclusionsThe assumptions required for a beneficial effect of hydroxychloroquine on 14 day mortality are difficult to sustain, while the assumptions required for hydroxychloroquine to be harmful are difficult to reject with confidence. Dexamethasone, by contrast, was beneficial under a wide range of plausible assumptions, and was only harmful if a nearly impossible assumption is met. More broadly, the SCQE reveals what inferences can be credibly supported by evidence from non-randomized uses of experimental therapies, making it a useful tool when randomized trials have not yet produced clear evidence or to provide corroborative evidence from different populations.

BACKGROUND People with HIV (PWH) are at an increased risk for adiposity and sarcopenia, despite effective antiretroviral therapy. Our objective was to compare the effects of prescribed exercise on body composition in older PWH and uninfected controls. SETTING Academic medical center. METHODS Sedentary PWH (n = 27) and uninfected controls (n = 28) aged 50-75 years completed 24 weeks of cardiovascular and resistance exercise. Participants completed 12 weeks of moderate-intensity exercise and then were randomized to moderate- or high-intensity exercise for 12 additional weeks. Total lean (LEAN) and fat mass (FAT), and visceral adipose tissue area (VAT) were measured using dual-energy x-ray absorptiometry at baseline and 24 weeks; baseline and intervention differences were compared by HIV serostatus using multivariable regression analyses adjusted for baseline values, age, and exercise adherence. RESULTS At baseline, PWH had significantly lower FAT (P = 0.003), but no significant differences in LEAN or VAT compared with controls (P > 0.20). Changes over 24 weeks were not significantly different by HIV serostatus, although controls tended to gain more LEAN (0.8 kg; range, 0-1.6 kg; P = 0.04] than PWH (0.6 kg; range, -0.2 to 1.4 kg; P = 0.12) and lose less FAT and VAT (controls: (-0.9 kg; range, -1.8 to 0.0 kg and -10.3 cm; range, -19.6, 1.0) cm; both P = 0.03 vs PWH: -2.0 kg; range, -2.9 to -1.1 kg and -17.7 cm; range, -27.1 to -8.2 cm; both P < 0.001). Exercise intensity differences were not apparent for LEAN, FAT, or VAT. CONCLUSIONS Exercise reduced total and visceral fat in older PWH and controls. Minimal gains in lean mass suggest that greater emphasis on resistance exercise may be needed to more effectively increase muscle in PWH.

ImportanceThere is a need to develop tools to differentiate COVID-19 from bacterial pneumonia at the time of clinical presentation before diagnostic testing is available.ObjectiveTo determine if the Ferritin-to-Procalcitonin ratio (F/P) can be used to differentiate COVID-19 from bacterial pneumonia.DesignThis case-control study compared patients with either COVID-19 or bacterial pneumonia, admitted between March 1 and May 31, 2020. Patients with COVID-19 and bacterial pneumonia co-infection were excluded.SettingA multicenter study conducted at three hospitals that included UCHealth and Phoebe Putney Memorial Hospital in the United States, and Yichang Central People’s Hospital in China.ParticipantsA total of 242 cases with COVID-19 infection and 34 controls with bacterial pneumonia.Main Outcomes and MeasuresThe F/P in patients with COVID-19 or with bacterial pneumonia were compared. Receiver operating characteristic analysis determined the sensitivity and specificity of various cut-off F/P values for the diagnosis of COVID-19 versus bacterial pneumonia.ResultsPatients with COVID-19 pneumonia had a lower mean age (57.11 vs 64.4 years, p=0.02) and a higher BMI (30.74 vs 27.15 kg/m2, p=0.02) compared to patients with bacterial pneumonia. Cases and controls had a similar proportion of women (47% vs 53%, p=0.5) and COVID-19 patients had a higher prevalence of diabetes mellitus (32.6% vs 12%, p=0.01). The median F/P was significantly higher in patients with COVID-19 (4037.5) compared to the F/P in bacterial pneumonia (802, pConclusions and RelevanceAn F/P ≥ 877 increases the likelihood of COVID-19 pneumonia compared to bacterial pneumonia. Further research is needed to determine if obtaining ferritin and procalcitonin simultaneously at the time of clinical presentation has improved diagnostic value. Additional questions include whether an increased F/P and/or serial F/P associates with COVID-19 disease severity or outcomes.

Antiretroviral therapy (ART) is associated with gain inParticipants from the Modena HIV Metabolic Clinic taking RAL, ATV/r, or DRV/r with at least 1 computed tomography (CT) scan were included. CT scans were reanalyzed for area and density of truncal fat and musculature. Multivariate models explored the effect of ART on fat and muscle density.One hundred six participants were receiving ATV/r, 48 DRV/r, and 141 RAL. In multivariate models (reference ATV/r), only DRV/r was associated with greater subcutaneous (SAT) and visceral adipose tissue (VAT) area, lower lateralis muscle density (more fat), and greater lateralis intermuscular fat area. Compared to ATV/r, RAL was independently associated with less psoas intermuscular fat area. Among all, greater paraspinal muscle density correlated with better physical function. No associations between ART group and physical function were seen among men; DRV/r was associated with stronger grip strength among women.DRV/r was associated with greater fat area and lower density of both fat and muscle, and RAL with less intermuscular psoas fat. Higher density psoas and paraspinal musculature were associated with better physical function, suggesting potential clinical relevance of these findings.

Made available in DSpace on 2021-06-25T12:17:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-01 Brazilian grants from SETI (Secretaria da Ciencia, Tecnologia e Ensino Superior do Parana) Ministry of Education Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Brazilian scholarship for a research internship at A.R.W.'s laboratory in Cleveland, USA Background: In 2019, the European Working Group on Sarcopenia in Older People (EWGSOP2) proposed low muscle strength as the primary outcome for sarcopenia diagnosis instead of low muscle mass, as proposed in 2010 (EWGSOP1). Therefore, the aim of this study was to compare the prevalence of sarcopenia using both EWGSOP1 and EWGSOP2 operational definitions in people living with HIV (PLHIV) and to determine the agreement and correlation between different tests proposed by EWGSOP2. Setting: Cross-sectional study, where 302 PLHIV (151 men), 51.7 +/- 9.0 years old were evaluated for the presence of sarcopenia using both EWGSOP1 and EWGSOP2 operational definitions. Methods: Appendicular skeletal muscle was estimated using bioimpedance analysis. Handgrip strength, chair stand, gait speed, and static balance were used as muscle function measures. Agreement was determined using Cohen kappa and Pearson correlation coefficient was calculated. Results: Sarcopenia prevalence was 4.3% using EWGSOP1 and 1.0% using EWGSOP2. Agreement for sarcopenia diagnosis between EWGSOP1 and EWGSOP2 was fair (k = 0.37, P < 0.01). From the 13 cases of sarcopenia diagnosed using EWGSOP1, only 3 cases (23.1%) were also diagnosed using EWGSOP2. A medium correlation (r = -0.32, P < 0.01) and poor agreement (k = 0.14, P < 0.01) between muscle strength tests (handgrip strength and chair stand) were observed. Concordance between handgrip and chair stand was observed in 11 participants only, whereas 65 participants were considered to have low muscle strength using chair stand but not using handgrip. Conclusions: Lower sarcopenia prevalence using EWGSOP2 and low agreement between EWGSOP1 and EWGSOP2 operational definitions in diagnosing sarcopenia were observed in PLHIV. Univ Estadual Londrina, Dept Phys Educ, Londrina, Parana, Brazil Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Res Campus,10900 Euclid Ave, Cleveland, OH 44106 USA Univ Estadual Londrina, Hlth Sci Ctr, Londrina, Parana, Brazil Salgado Inst Integral Hlth, Londrina, Parana, Brazil Univ Estadual Londrina, Biol Sci Ctr, Londrina, Parana, Brazil State Univ Sao Paulo, Dept Phys Educ, Presidente Pmdente, SP, Brazil Univ Colorado, Anschutz Med Campus, Aurora, CO USA State Univ Sao Paulo, Dept Phys Educ, Presidente Pmdente, SP, Brazil CAPES: 88881.132132/2016-01

Background In this study, we evaluate associations between cumulative antiretroviral adherence/exposure, quantified using tenofovir diphosphate (TFV-DP) in dried blood spots (DBS), and human immunodeficiency virus (HIV)-related aging factors. Methods This is a cross-sectional analysis of younger (ages 18–35) and older (ages ≥60) persons with HIV (PWH) taking TFV disoproxil fumarate. Tenofovir diphosphate concentrations were quantified in DBS. Linear and logistic regression models were used to evaluate associations between TFV-DP and bone mineral density (BMD), physical function, frailty, and falls. Results Forty-five PWH were enrolled (23 younger, 22 older). Every 500 fmol/punch (equivalent to an increase in ~2 doses/week) increase in TFV-DP was associated with decreased hip BMD (−0.021 g/cm2; 95% confidence interval [CI], −0.040 to −0.002; P = .03). Adjusting for total fat mass, every 500 fmol/punch increase in TFV-DP was associated with higher odds of Short Physical Performance Battery impairment (score ≤10; adjusted odds ratio [OR], 1.6; 95% CI, 1.0–2.5; P = .04). Every 500 fmol/punch increase in TFV-DP was associated with slower 400-meter walk time (14.8 seconds; 95% CI, 3.8–25.8; P = .01) and remained significant after adjusting for age, lean body mass, body mass index (BMI), and fat mass (all P ≤ .01). Every 500 fmol/punch increase in TFV-DP was associated with higher odds of reporting a fall in the prior 6 months (OR, 1.8; 95% CI, 1.1–2.8; P = .02); this remained significant after adjusting for age, lean body mass, BMI, and total fat mass (all P, The associations between tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) and human immunodeficiency virus (HIV)-related aging factors was evaluated. Higher TFV-DP levels were found to be associated with impaired physical function and fracture risk.

BACKGROUND Frailty and physical function impairments occur at an earlier than expected age in people with HIV (PWH). The goal of this study was to determine which tools or combination of tools assessing frailty/physical function were most predictive of mortality in a middle-aged population of PWH. METHODS Using electronic health records, we determined survival, death, or loss to follow-up for 359 PWH, aged 45-65 years originally enrolled in a 2009-2010 cross-sectional cohort study. The predictive accuracy of various physical function measures [frailty score, Veterans Aging Cohort Study (VACS) index, 400-m walk, Short Physical Performance Battery (SPPB), grip strength, and falls] were compared using integrated time-dependent receiver operating characteristic area under the curve (AUC) in single variable models. Two-variable models were compared with the best single-variable model to determine if AUC improved with additional physical function variables. RESULTS At 8-year follow-up, frailty, 400-m walk pace, SPPB, chair rise pace, VACS score, and falls were associated with increased hazard of mortality; grip strength was only predictive in sex-adjusted models. The VACS index and 400-m walk pace were the best individual predictors of mortality with time-dependent receiver operating characteristic AUC scores of 0.82, followed by SPPB (0.73), chair-rise pace (0.68), falls (0.65), frailty (0.63), and grip strength (0.55). Addition of the 400-m walk to VACS index yielded the only significant improvement in the prediction of survival compared with the VACS index alone (P = 0.04). CONCLUSION Our study highlights several clinically applicable physical function measures predictive of mortality in middle-aged PWH that can be tailored to specific patient subpopulations and clinical or research encounters.