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ObjectivesTo establish healthcare professionals’ (HCPs) views about clinical roles, and the barriers and enablers to delivery of diabetes care for people with severe mental illness (SMI).DesignCross-sectional, postal and online survey.SettingTrusts within the National Health Service, mental health and diabetes charities, and professional bodies.ParticipantsHCPs who care for people with type 2 diabetes mellitus (T2DM) and/or SMI in the UK.Primary and secondary outcome measuresThe barriers, enablers and experiences of delivering T2DM care for people with SMI, informed by the Theoretical Domains Framework.ResultsRespondents were 273 HCPs, primarily mental health nurses (33.7%) and psychiatrists (32.2%). Only 25% of respondents had received training in managing T2DM in people with SMI. Univariate analysis found that mental health professionals felt responsible for significantly fewer recommended diabetes care standards than physical health professionals (PConclusionsThis survey indicates that despite current guidelines, diabetes care in mental health settings remains peripheral. Even when diabetes care is perceived as part of an HCP’s role, various individual and organisational barriers to delivering recommended T2DM care standards to people with SMI are experienced.

Objective: Dietary fructose is implicated in metabolic syndrome, but intervention studies are confounded by positive caloric balance, changes in adiposity, or artifactually high amounts. This study determined whether isocaloric substitution of starch for sugar would improve metabolic parameters in Latino (n 527) and African-American (n 516) children with obesity and metabolic syndrome. Methods: Participants consumed a diet for 9 days to deliver comparable percentages of protein, fat, and carbohydrate as their self-reported diet; however, dietary sugar was reduced from 28% to 10% and substituted with starch. Participants recorded daily weights, with calories adjusted for weight maintenance. Participants underwent dual-energy X-ray absorptiometry and oral glucose tolerance testing on Days 0 and 10. Biochemical analyses were controlled for weight change by repeated measures ANCOVA. Results: Reductions in diastolic blood pressure (25 mmHg; P 50.002), lactate (20.3 mmol/L; P

Consumption of high-fructose diets promotes hepatic fatty acid synthesis (de novo lipogenesis [DNL]) and an atherogenic lipid profile. It is unclear whether these effects occur independent of positive energy balance and weight gain.We compared the effects of a high-fructose, (25% of energy content) weight-maintaining diet to those of an isocaloric diet with the same macronutrient distribution but in which complex carbohydrate (CCHO) was substituted for fructose.Eight healthy men were studied as inpatients for consecutive 9-day periods. Stable isotope tracers were used to measure fractional hepatic DNL and endogenous glucose production (EGP) and its suppression during a euglycemic-hyperinsulinemic clamp. Liver fat was measured by magnetic resonance spectroscopy.Weight remained stable. Regardless of the order in which the diets were fed, the high-fructose diet was associated with both higher DNL (average, 18.6 ± 1.4% vs 11.0 ± 1.4% for CCHO; P = .001) and higher liver fat (median, +137% of CCHO; P = .016) in all participants. Fasting EGP and insulin-mediated glucose disposal did not differ significantly, but EGP during hyperinsulinemia was greater (0.60 ± 0.07 vs 0.46 ± 0.06 mg/kg/min; P = .013) with the high-fructose diet, suggesting blunted suppression of EGP.Short-term high-fructose intake was associated with increased DNL and liver fat in healthy men fed weight-maintaining diets.

BackgroundOral tenofovir disoproxil fumarate (TDF) for HIV prevention and treatment is associated with decreases in bone mineral density (BMD). Previous reports suggest that these changes may be reversible after discontinuation of TDF.SettingA metabolic substudy of 498 participants in a randomized, placebo-controlled HIV prevention trial of oral coformulated TDF with emtricitabine (TDF/FTC, Truvada) for HIV pre-exposure prophylaxis (PrEP) enrolling a global sample of men who have sex with men and trans women.MethodsParticipants underwent dual X-ray absorptiometry to quantify bone mineral density (BMD) in the hip and spine during PrEP and at 2 visits after stopping (median of 23 and 79 weeks post-PrEP, respectively). Results are stratified by pharmacologic measure of TDF/FTC adherence.ResultsThere was no significant difference in change in hip/spine BMD at any time point between placebo and those with low adherence. Adherent participants had a mean (standard error) BMD change at TDF/FTC discontinuation of -1.02% (0.24) in the hip and -1.84% (0.36) in the spine. After stop, annualized BMD increases of 1.13% per year (0.27) in hip and 1.81% per year (0.36) in spine BMD were observed in adherent participants compared with 0.19% (0.16) and 0.74% (0.21) in the placebo group, respectively (P = 0.003, both comparisons). On average, BMD returned to baseline levels by 1 year after PrEP stop. Recovery was consistent across age, baseline BMD z-score, and treatment duration.ConclusionsMean BMD returns to baseline levels within 12-18 months after TDF-based PrEP discontinuation in both hip and spine with consistency across participant subgroups.Clinical trials registrationclinicaltrials.gov NCT00458393.

Background People with severe mental illness (SMI) must receive early interventions to prevent mental health deterioration or relapse. Telecommunications and other technologies are increasingly being used to assist in health care delivery using “telehealth,” which includes telephones and mobile phones, computers, remote sensors, the internet, and other devices, to provide immediate real-time information to service users to improve the management of chronic health conditions. Some initial findings have suggested that technology could improve the quality of life of people with SMI. Objective In this systematic review, we aimed to identify the various uses and efficacy of telehealth technology for SMI. Methods We systematically searched electronic databases from inception to March 2016 (MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database, Health Technology Assessment, CINAHL Plus, and NHS Economic Evaluations Database) to identify randomized controlled trials evaluating telehealth for adults with SMI published in English. Additional literature was identified through searching reference lists of key articles. The articles meeting the inclusion criteria were systematically reviewed and assessed for quality and risk of bias. Results Our search identified 31 articles describing 29 trials as eligible for the review. The included studies evaluated the use of computers to deliver cognitive rehabilitation (15 trials), patient education (3 trials), and Web-based self-management interventions (2 trials) and to support consultations (1 trial). Virtual reality was used to simulate work and social situations (2 trials) and to deliver cognitive training (1 trial). Telephones were used to prompt service users to take medications (3 trials) and to report symptoms to their health care team (1 trial). Remote sensors were used to monitor medication use (1 trial). Telephone support was found effective in improving medication adherence and reducing the severity of symptoms and inpatient days. Computer-assisted cognitive rehabilitation was effective in improving cognitive function. The impact of telehealth on other outcomes was inconsistent. The results of this review should be taken in the context of varied quality in study design, with only 5 studies demonstrating a low risk of bias. Conclusions A growing variety of telehealth technologies are being used to support the management of SMI. Specific technology types have been found to be effective for some outcomes (eg, telephone and remote medication monitoring for adherence to treatment), while other types of telehealth technologies (eg, delivery of patient education using computers) had no benefit over traditional nurse-based methods and were less acceptable to patients. Further research is warranted to establish the full potential benefits of telehealth for improving the quality of life in people with SMI, acceptability from the service user perspective, and cost-effectiveness. The findings of this review are limited by the poor quality of many of the studies reviewed.

BACKGROUND People with severe mental illness (SMI) must receive early interventions to prevent mental health deterioration or relapse. Telecommunications and other technologies are increasingly being used to assist in health care delivery using “telehealth,” which includes telephones and mobile phones, computers, remote sensors, the internet, and other devices, to provide immediate real-time information to service users to improve the management of chronic health conditions. Some initial findings have suggested that technology could improve the quality of life of people with SMI. OBJECTIVE In this systematic review, we aimed to identify the various uses and efficacy of telehealth technology for SMI. METHODS We systematically searched electronic databases from inception to March 2016 (MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database, Health Technology Assessment, CINAHL Plus, and NHS Economic Evaluations Database) to identify randomized controlled trials evaluating telehealth for adults with SMI published in English. Additional literature was identified through searching reference lists of key articles. The articles meeting the inclusion criteria were systematically reviewed and assessed for quality and risk of bias. RESULTS Our search identified 31 articles describing 29 trials as eligible for the review. The included studies evaluated the use of computers to deliver cognitive rehabilitation (15 trials), patient education (3 trials), and Web-based self-management interventions (2 trials) and to support consultations (1 trial). Virtual reality was used to simulate work and social situations (2 trials) and to deliver cognitive training (1 trial). Telephones were used to prompt service users to take medications (3 trials) and to report symptoms to their health care team (1 trial). Remote sensors were used to monitor medication use (1 trial). Telephone support was found effective in improving medication adherence and reducing the severity of symptoms and inpatient days. Computer-assisted cognitive rehabilitation was effective in improving cognitive function. The impact of telehealth on other outcomes was inconsistent. The results of this review should be taken in the context of varied quality in study design, with only 5 studies demonstrating a low risk of bias. CONCLUSIONS A growing variety of telehealth technologies are being used to support the management of SMI. Specific technology types have been found to be effective for some outcomes (eg, telephone and remote medication monitoring for adherence to treatment), while other types of telehealth technologies (eg, delivery of patient education using computers) had no benefit over traditional nurse-based methods and were less acceptable to patients. Further research is warranted to establish the full potential benefits of telehealth for improving the quality of life in people with SMI, acceptability from the service user perspective, and cost-effectiveness. The findings of this review are limited by the poor quality of many of the studies reviewed.

BACKGROUND HIV-infected (HIV-pos) male children/youth showed lower bone mineral density at sexual maturity than HIV-uninfected (HIV-neg) females. It is not known whether complications of HIV disease, including abnormal body fat distribution, contribute to lower bone accrual in male HIV-pos adolescents. METHODS In a cross-sectional study, we evaluated the relationship between body composition (fat and lean mass) and bone mass in HIV-pos and HIV-neg children/youth and determined if it is modified by HIV status and sex. We used generalized estimating equations to simultaneously model the effect of fat/lean mass on multiple bone outcomes, including total body bone mineral density and bone mineral content and spine bone mineral density. We evaluated effect modification by HIV and sex. RESULTS The analysis cohort consisted of 143 HIV-neg and 236 HIV-pos, of whom 55% were black non-Hispanic and 53% were male. Ages ranged from 7 to < 25 years. Half of the children/youth were at Tanner stage 1 and 20% at Tanner 5. Fat mass was more strongly positively correlated with bone mass in HIV-neg than HIV-pos children/youth and these relationships were more evident for total body bone than spine outcomes. Within HIV strata, fat mass and bone were more correlated in female than male children/youth. The relationship between lean mass and bone varied by sex, but not by HIV status. CONCLUSIONS HIV disease diminishes the positive relationship of greater fat mass on bone mass in children/youth. Disruptions in body fat distribution, which are common in HIV disease, may have an impact on bone accretion during pubertal development.

Background:Growth hormone (GH) is known to affect insulin and glucose metabolism. Blocking its effects in acromegalic patients improves diabetes and glucose metabolism. We aimed to determine the effect of pegvisomant, a GH receptor antagonist, on insulin resistance, endogenous glucose production (EGP) and lipolysis in insulin resistant non-diabetic men. Methods:Four men between the ages of 18-62 with a BMI of 18-35kg/m2, with insulin resistance as defined by a HOMA-IR > 2.77, were treated for four weeks with pegvisomant 20 mg daily. Inpatient metabolic assessments were performed before and after treatment. The main outcome measurements were: change after pegvisomant therapy in insulin sensitivity as measured by hyperinsulinemic euglycemic clamp; and EGP and lipolysis assessed by stable isotope tracer techniques.Results:Insulin like growth factor-1 (IGF-1) concentrations decreased from 134.0 ± 41.5 (mean ± SD) to 72.0 ± 11.7 ng/mL (p = 0.04) after 4 weeks of therapy. Whole body insulin sensitivity index (M/I 3.2 ± 1.3vs.3.4 ± 2.4;P= 0.82), as well as suppression of EGP (89.7 ± 26.9vs.83.5 ± 21.6%; p = 0.10) and Ra glycerol (59.4 ± 22.1%vs.61.2 ± 14.4%; p = 0.67) during the clamp were not changed significantly with pegvisomant treatment.Conclusions:Blockade of the GH receptor with pegvisomant for four weeks had no significant effect on insulin/glucose metabolism in a small phase II pilot study of non-diabetic insulin resistant participants without acromegaly.

Background\ud People with diabetes and severe mental illness (SMI) experience poorer outcomes than those with diabetes alone. To improve outcomes, it is necessary to understand the difficulties that people with SMI experience in managing their diabetes.\ud \ud Aims\ud To identify barriers and enablers to effective diabetes self-management experienced by people with SMI and type 2 diabetes.\ud \ud Method\ud Qualitative methodology using semi-structured interviews was employed. Development of the interview topic guide and analysis of the transcripts was informed by the Theoretical Domains Framework (TDF) for behaviour change, which consists of fourteen theoretical domains that have been found to influence behaviour. \ud \ud Results\ud Fourteen people with SMI and type 2 diabetes took part in the study. Participants considered diabetes self-management to be important, were aware of the risks of poor diabetes control but struggled to follow recommended advice, particularly if their mental health was poor. Support from family and health professionals was considered an important enabler of diabetes self-management. \ud \ud Conclusions\ud New approaches are required to support diabetes self-management in people with SMI. This study identified some of the important domains that may be targeted in new interventions.

Background & Aims Consumption of sugar is associated with obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease, and cardiovascular disease. The conversion of fructose to fat in liver (de novo lipogenesis [DNL]) may be a modifiable pathogenetic pathway. We determined the effect of 9 days of isocaloric fructose restriction on DNL, liver fat, visceral fat (VAT), subcutaneous fat, and insulin kinetics in obese Latino and African American children with habitual high sugar consumption (fructose intake >50 g/d). Methods Children (9−18 years old; n = 41) had all meals provided for 9 days with the same energy and macronutrient composition as their standard diet, but with starch substituted for sugar, yielding a final fructose content of 4% of total kilocalories. Metabolic assessments were performed before and after fructose restriction. Liver fat, VAT, and subcutaneous fat were determined by magnetic resonance spectroscopy and imaging. The fractional DNL area under the curve value was measured using stable isotope tracers and gas chromatography/mass spectrometry. Insulin kinetics were calculated from oral glucose tolerance tests. Paired analyses compared change from day 0 to day 10 within each child. Results Compared with baseline, on day 10, liver fat decreased from a median of 7.2% (interquartile range [IQR], 2.5%−14.8%) to 3.8% (IQR, 1.7%−15.5%) ( P 3 (IQR, 85−145 cm 3 ) to 110 cm 3 (IQR, 84–134 cm 3 ) ( P P P Conclusions Short-term (9 days) isocaloric fructose restriction decreased liver fat, VAT, and DNL, and improved insulin kinetics in children with obesity. These findings support efforts to reduce sugar consumption. ClinicalTrials.gov Number: NCT01200043.

Aims and Objectives: To explore the effect contact with a heart failure nurse can have on patients' illness beliefs, mood and quality of life. \ud \ud Background: There is growing interest in patients' illness beliefs and the part they play in a patients understanding of chronic disease. \ud \ud Design: Secondary analysis on two independent datasets. Patients were recruited from five UK hospitals, four in London and one in Sussex. Patients were recruited from an inpatient and outpatient setting. The first dataset recruited 174 patients with newly diagnosed heart failure, whilst the second dataset recruited 88 patients with an existing diagnosis of heart failure. \ud \ud Methods: Patients completed the Minnesota Living with Heart Failure Questionnaire, Hospital Anxiety and Depression Scale, Illness Perception Questionnaire and the Treatment Representations Inventory at baseline and six months. We used a linear regression model to assess the association that contact with a heart failure nurse had on mood, illness beliefs and quality of life over a six-month period. \ud \ud Results: Patients who had contact with a heart failure nurse were more satisfied with their treatment and more likely to believe that their heart failure was treatable. Contact with a heart failure nurse did not make a statistically significant difference to mood or quality of life. \ud \ud Conclusions: This study has shown that contact with a heart failure nurse can improve patient satisfaction with treatment decisions but has less influence on a patient's beliefs about their personal control, treatment control and treatment concerns. With appropriate support, skills and training, heart failure nurses could play an important role in addressing individual patient's beliefs. There is a need to further investigate this. \ud \ud Relevance to clinical practice: Exploring patients' illness beliefs and mood could help to enhance person-centred care. Heart failure nurses would need additional training in the techniques used. © 2014 John Wiley & Sons Ltd.

Due to their similar aetiologies, cardiovascular disease (CVD) and erectile dysfunction (ED) are closely linked, with the prevalence of ED being approximately 75% for individuals at high risk of CVD. ED can have a detrimental effect on quality of life not only for the individual but also his sexual partner which in turn impacts upon their intimate relationship. Some CVD medications have been found to have a negative effect on erectile function and therefore act as an influential factor for the cessation of important CVD medication. Low adherence to CVD medication has been linked to increased health costs, hospitalizations and importantly, a higher risk of mortality. Research has shown that men find it difficult to seek medical help in relation to ED which is also compounded by the notion that health care providers do not address sexual issues adequately. Patients' beliefs about CVD medication are modifiable and therefore an opportunity exists not only for health care providers to facilitate discussions in relation to ED and medication adherence but also encompass an opportunity to increase adherence to CVD medication through intervention.

We conducted cross-sectional, multicenter studies in HIV-positive young women and men to assess metabolic and morphologic complications from tobacco smoking in 372 behaviorally infected HIV-positive youth, aged 14–25 years. Measurements included self-reported tobacco use, fasting lipids, glucose, fat distribution, and bone mineral density (BMD; dual-energy X-ray absorptiometry scans). Overall, 144 (38.7%) self-reported smoking tobacco and 69 (47.9%) of these reported smoking greater than five cigarettes per day. Smokers versus nonsmokers had lower mean total cholesterol (146.0 versus 156.1 mg/dL;P<0.01) and lower mean total body fat percent (24.1% versus 27.2%,P=0.03). There was no difference between smokers and nonsmokers in fasting glucose or BMD. There appear to be only minimal effects from tobacco smoking on markers of cardiac risk and bone health in this population of HIV-positive youth. While these smokers may not have had sufficient exposure to tobacco to detect changes in the outcome measures, given the long-term risks associated with smoking and HIV, it is critical that we encourage HIV-positive youth smokers to quit before the deleterious effects become apparent.

Background Changes in the multiple mechanisms that regulate glucose metabolism after gastric bypass (RYGB) are still being unveiled. The objective of this study was to compare the changes of glucose and pancreatic hormones [C-peptide, glucagon, and pancreatic polypeptide (PP)] during a meal tolerance test (MTT) and steady-state insulin and free fatty acid (FFA) concentrations during euglycemic–hyperinsulinemic clamp 14 days and 6 months after RYGB in morbidly obese nondiabetic patients. Methods Two groups were studied at baseline and at 14 days: the RYGB followed by caloric restriction group (RYGB, n=12) and the equivalent caloric restriction alone group (Diet, n=10), to control for energy intake and weight loss. The RYGB group was studied again at 6 months to assess the changes after substantial weight loss. During MTT, the early and overall changes in glucose and pancreatic hormone concentrations were determined, and during the clamp, steady-state insulin and FFA concentrations were assessed. Results After 14 days, RYGB patients had enhanced postprandial glucose, C-peptide, and glucagon responses, and decreased postprandial PP concentrations. Steady-state insulin concentrations were decreased at 14 days only in RYGB patients, and FFA increased in both groups. Six months after RYGB and substantial weight loss, the decrease in insulin concentrations during clamp persisted, and there were further changes in postprandial glucose and glucagon responses. FFA concentrations during clamp were significantly lower at 6 months, relative to presurgical values. Conclusions In morbidly obese nondiabetic patients, RYGB produces early changes in postmeal glucose, C-peptide, glucagon, and PP responses, and it appears to enhance insulin clearance early after RYGB and improve insulin sensitivity in adipose tissue at 6 months postsurgery. The early changes cannot be explained by caloric restriction alone.

Background We aimed to define the relative importance of renal and endocrine changes in tenofovir disoproxil fumarate (TDF)-related bone toxicity. Methods In a study of daily TDF/emtricitabine (FTC) preexposure prophylaxis (PrEP) in human immunodeficiency virus (HIV)-uninfected young men who have sex with men, we measured changes from baseline in blood and urine markers of the parathyroid hormone (PTH)-vitamin D-fibroblast growth factor 23 (FGF23) axis, creatinine, and renal tubular reabsorption of phosphate (TRP). We explored the relationship of those variables to changes in bone mineral density (BMD). Tenofovir-diphosphate (TFV-DP) in red blood cells was used to categorize participants into high and low drug exposure groups. Results There were 101 participants, median age 20 years (range 15 to 22). Compared with low drug exposure, high-exposure participants showed increase from baseline in PTH and decline in FGF23 by study week 4, with no differences in creatinine, phosphate, or TRP. At 48 weeks, the median (interquartile range) percent decline in total hip BMD was greater in those with high- compared to low- exposure (-1.59 [2.77] vs +1.54 [3.34] %, respectively; P = .001); in high-exposure participants, this correlated with week 4 TFV-DP (inversely; r = -0.60, P = .002) and FGF23 (directly; r = 0.42; P = .039) but not other variables. Conclusions These findings support the short-term renal safety of TDF/FTC PrEP in HIV-seronegative young men and suggest that endocrine disruption (PTH-FGF23) is a primary contributor to TDF-associated BMD decline in this age group. Clinical trials registration NCT01769469.

The technique of body composition by dual-energy X-ray absorptiometry (DXA) has been used for several years in the research environment. Its ability to accurately and precisely measure lean, fat, and mineral composition in various body compartments has been well validated. Furthermore, the technique is widely available to clinical patients on existing DXA instruments throughout the world through the use of specific software packages and scanning algorithms. There have been few clear statements regarding the clinical indications for body composition measurement in patients outside the research setting. This is in part because of the lack of specific documented interventions that would be affected by body composition test results, beyond usual clinical advice. We have examined a few of the most common, specific scenarios (HIV therapy, sarcopenia, bariatric surgery, obesity) and proposed indications for body composition assessment. We have also discussed contraindications to body composition testing.

P REVENTION S CIENCE An HIV Preexposure Prophylaxis Demonstration Project and Safety Study for Young MSM Sybil G. Hosek, PhD,* Bret Rudy, MD,† Raphael Landovitz, MD,‡ Bill Kapogiannis, MD,§ George Siberry, MD,§ Brandy Rutledge, PhD,k Nancy Liu, MPH,k Jennifer Brothers, MPH,* Kathleen Mulligan, PhD,¶ Gregory Zimet, PhD,# Michelle Lally, MD,** Kenneth H. Mayer, MD,†† Peter Anderson, PharmD,‡‡ Jennifer Kiser, PharmD,‡‡ James F. Rooney, MD,§§ and Craig M. Wilson, MD,kk the Adolescent Trials Network (ATN) for HIV/AIDS Interventions Background: Young men who have sex with men (YMSM) are a key population for implementation of preexposure prophylaxis (PrEP) interventions. This open-label study examined adherence to PrEP and assessed sexual behavior among a diverse sample of YMSM in 12 US cities. Methods: Eligible participants were 18- to 22-year-old HIV- uninfected MSM who reported HIV transmission risk behavior in the previous 6 months. Participants were provided daily tenofovir disoproxil fumarate/emtricitabine (Truvada). Study visits occurred at baseline, monthly through week 12, and then quarterly through week 48. Dried blood spots were serially collected for the quantification of tenofovir diphosphate (TFV-DP). Results: Between March and September 2013, 2186 individuals were approached and 400 were found to be preliminarily eligible. Of those 400, 277 were scheduled for an in-person screening visit and 200 were enrolled (mean age = 20.2; 54.5% black, 26.5% Latino). Diagnosis of sexually transmitted infections, including urethral and rectal chlamydial/gonococcal infection and syphilis, at baseline was 22% and remained high across visits. At week 4, 56% of participants had TFV-DP levels consistent with $4 pills per week. By week 48, 34% of participants had TFV-DP levels consistent with $4 pills per week, with a noticeable drop-off occurring at week 24. Four HIV seroconversions occurred on study (3.29/100 person-years). Con- domless sex was reported by .80% of participants, and condomless anal sex with last partner was associated with higher TFV-DP levels. Conclusions: Acceptability of PrEP was high, and most partic- Received for publication February 6, 2016; accepted August 26, 2016. From the *John Stroger Hospital of Cook County, Chicago, IL; †New York University Medical Center, New York, NY; ‡University of California Los Angeles, Los Angeles, CA; §NICHD/MPIDB, Bethesda, MD; kWestat, Rockville, MD; ¶University of California San Francisco, San Francisco, CA; #Indiana University, Indianapolis, IN; **Alpert Medical School of Brown University and Lifespan Hospital System, Providence, RI; ††Fenway Health, Boston, MA; ‡‡University of Colorado, Denver, CO; §§Gilead Sciences, Foster City, CA; and kkUniversity of Alabama at Birmingham, Birmingham, AL. This study was funded under cooperative agreements U01 HD040533 and U01 HD040474 from the National Institutes of Health through the Eunice Kennedy Shriver National Institute of Child Health and Human Devel- opment with supplemental funding from the National Institute on Drug Abuse and National Institute of Mental Health. Study drug was donated by Gilead Sciences, Inc., along with supplemental funds for a portion of the dried blood spot testing. Supported by The Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) from the National Institutes of Health (U01 HD 040533 and U01 HD 040474) through the National Institute of Child Health and Human Development (B.K. and S. Lee), with supplemental funding from the National Institutes on Drug Abuse (K. Davenny and S. Kahana) and Mental Health (P. Brouwers, S. Allison). Study drug was donated by Gilead Sciences. K.M. has received unrestricted research grants from Gilead Sciences and ViiV. P.A. receives donated study drug and contract work from Gilead. J. F.R. is employed by Gilead Sciences, the maker of the study drug. The remaining authors have no funding or conflicts of interest to disclose. The comments and views of the authors do not necessarily represent the views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Correspondence to: Sybil G. Hosek, PhD, Department of Psychiatry, John Stroger Hospital of Cook County, 1900 W Polk Street, room 854, Chicago, IL 60612 (e-mail: shosek@cookcountyhhs.org). Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. ipants achieved protective drug levels during monthly visits. As visit frequency decreased, so did adherence. YMSM in the United States may need PrEP access in youth-friendly settings with tailored adherence support and potentially augmented visit schedules. Key Words: preexposure prophylaxis, youth, men who have sex with men (J Acquir Immune Defic Syndr 2017;74:21–29) INTRODUCTION Young men who have sex with men (YMSM), particu- larly black and Latino YMSM, are the group most affected by HIV in the United States, 1 making them a key domestic population for implementation of HIV preexposure prophylaxis (PrEP) interventions. Based on evidence from multiple clinical trials of PrEP, 2–4 the US Food and Drug Administration approved daily use of tenofovir disoproxil fumarate/emtricita- bine (TDF/FTC) for the prevention of sexually acquired HIV in July 2012. In anticipation of this new drug indication, several open-label demonstration projects were launched to evaluate PrEP safety and adherence outside of a placebo-controlled trial setting; effective PrEP implementation strategies for specific at- risk populations are also being evaluated. Although not placebo controlled, the more recent PROUD study used an open-label randomized controlled design of either immediate or delayed PrEP to pilot test the implementation of PrEP in the public health system of the J Acquir Immune Defic Syndr Volume 74, Number 1, January 1, 2017 www.jaids.com | Copyright O 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

Aims The aim of this study was to identify the barriers and enablers to effective insulin selftitration in type 2 diabetes. Methods A qualitative semi-structured interview approach was employed. Questions were structured according to the Theoretical Domains Framework, which outlines 14 domains that can act as barriers and enablers to changing behaviour. Interviews were audio-recorded and transcribed verbatim. The data were coded according to the 14 domains, belief statements were created within each domain and a frequency count of the most reported barriers and enablers were then calculated. Analyses were conducted by two researchers, and discrepancies agreed with a third researcher. Results Eighteen adults with type 2 diabetes took part in an interview. A majority were South Asian (n=8), men (n=12), on average age 61 years old. Average duration of diabetes was 16 years and time on insulin 9 years. Inter-rater reliability for each of the domains varied (29%-100%). The most frequently reported domains were Social Influence and Beliefs about Consequences; the least frequently reported were Optimism and Reinforcement. Participants reported receiving support to self-titrate from a range of sources. Self-titrating was perceived to have a range of both positive and negative consequences, as was not titrating. Conclusions The findings highlight that participants experienced a range of barriers and enablers when attempting to self-titrate. Improved education and training when initiating insulin treatment among adults with type 2 diabetes, and throughout their journey on insulin therapy could help people identify and address these barriers in order to optimise self-titration. Novelty statement • This study is the first to comprehensively explore the reasons people with insulintreated type 2 diabetes struggle to self-titrate their insulin, using an established theoretical framework. • Important factors in facilitating self-titration were support from healthcare professionals and family members, having a target blood glucose reading and strategies to achieve this. • Barriers to self-titrating included difficulties experienced when at work or on holiday and concerns about the consequences of an increasing insulin dose. Holding strong but erroneous intentions to self-titrate, suggested a lack of knowledge about self-titration algorithms. • Providing educational resources and training when initiating insulin treatment in type 2 diabetes and throughout treatment, in order to address these barriers and enhance these facilitators is vital.

Background The purpose of this study was to explore the barriers and facilitators healthcare professionals experience when managing type 2 diabetes in people with severe mental illness (SMI). Methods A qualitative semi-structured interview approach was employed. Questions were structured according to the Theoretical Domains Framework (TDF), which outlines 14 domains that can act as barriers and facilitators to changing behaviour. Interviews were audio-recorded and transcribed verbatim. The data were coded according to the 14 domains of the TDF, belief statements were created within each domain and the most relevant belief statements within each domain identified through a consensus approach. Analyses were conducted by two researchers, and discrepancies agreed with a third researcher. Results Sixteen healthcare professionals, from a range of services, involved in the care of people with type 2 diabetes and SMI took part in an interview. Inter-rater reliability for each of the domains varied (25 %-74 %). All fourteen domains were deemed relevant, with 42 specific beliefs identified as important to the target behaviour. Participants identified having relevant knowledge and skills for diabetes management, prioritising this area of health, and reviewing health behaviours to develop action plans, as particularly important. At an organisational level, integrated care provision and shared information technology (IT) services between mental health and physical services, and clearly defined roles and responsibilities for the different professions, with designated time to undertake the work were identified as crucial. Conclusions The findings highlight that healthcare professionals’ experience a range of barriers and enablers when attempting to manage type 2 diabetes in people with SMI. These include organisational factors and individual beliefs, suggesting that interventions need to be targeted at both an organisation and individual level in order to change behaviour. Further work is needed to model these relationships in a larger sample of participants in line with the MRC guidance for developing complex interventions. Electronic supplementary material The online version of this article (doi:10.1186/s12888-016-0942-2) contains supplementary material, which is available to authorized users.

Background:\ud People with severe mental illness are twice as likely to develop type 2 diabetes asthose without severe mental illness. Treatment guidelines for type 2 diabetes recommend that structured education should be integrated into routine care and should be offered to all.However, for people with severe mental illness, physical health may be a low priority, and motivation to change may be limited. These additional challenges mean that the findings reported in previous systematic reviews of diabetes self management interventions may not be generalised to those with severe mental illness, and that tailored approaches to effective diabetes education may be required for this population.\ud \ud Objectives:\ud To assess the effects of diabetes self management interventions specifically tailored for people with type 2 diabetes and severe mental illness.\ud \ud Search methods:\ud We searched the Cochrane Library, MEDLINE, EMBASE, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature(CINAHL), the International Clinical Trials Registry Platform (ICTRP) Search Portal, ClinicalTrials.gov and grey literature. The date of the last search of all databases was 07 March 2016. Selection criteria Randomised controlled trials of diabetes self management interventions for people with type 2 diabetes and severe mental illness.\ud \ud Data collection and analysis:\ud Two review authors independently screened abstracts and full-text articles, extracted data and conducted the risk of bias assessment. We used a taxonomy of behaviour change techniques and the framework for behaviour change theory to describe the theoretical basis of the interventions and active ingredients. We used the GRADE method (Grades of Recommendation, Assessment, Development and Evaluation Working Group) to assess trials for overall quality of evidence. \ud \ud Main results:\ud We included one randomised controlled trial involving 64 participants with schizophrenia or schizoaffective disorder. The average age of participants was 54 years; participants had been living with type 2 diabetes for on average nine years, and with their psychiatric diagnosis since they were on average 28 years of age. Investigators evaluated the 24-week Diabetes Awareness and Rehabilitation Training(DART) programme in comparison with usual care plus information (UCI). Follow-up after trial completion was six months. Risk of bias was mostly unclear but was high for selective reporting. Trial authors did not report on diabetes-related complications, all-cause mortality, adverse events, health-related quality of life nor socioeconomic effects. Twelve months of data on self care behaviours as measured by total energy expenditure showed a mean of 2148 kcal for DART and 1496 kcal for UCI (52 participants; very low-quality evidence), indicating no substantial improvement. The intervention did not have a substantial effect on glycosylated haemoglobin A1c (HbA1c) at 6 or 12 months of follow-up (12-month HbA1c data 7.9% for DART vs 6.9% for UCI; 52 participants; very low-quality evidence). Researchers noted small improvements in body mass index immediately after the intervention was provided and at six months, along with improved weight post intervention. Diabetes knowledge and self efficacy improved immediately following receipt of the intervention, and knowledge also at six months. The intervention did not improve blood pressure.\ud \ud Authors’ conclusions:\ud Evidence is insufficient to show whether type 2 diabetes self management interventions for people with severe mental illness are effective in improving outcomes. Researchers must conduct additional trials to establish efficacy, and to identify the active ingredients in these interventions and the people most likely to benefit from them.

This is the peer reviewed version of the following article: J. Jones, et al, ‘Severe mental illness and type 2 diabetes: using theory and research evidence to develop complex behaviour change interventions’, Journal of Psychiatric and Mental Health Nursing, Vol. 23 (5): 312-321, June 2016, which has been published in final form at http://dx.doi.org/10.1111/jpm.12311. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. © 2016 John Wiley & Sons Ltd.

Accumulating evidence suggests that rates of low bone mass are greater in HIV-infected males than females. Of eleven biomarkers assessed by sex and HIV-status, HIV-infected males had increased levels of soluble CD14 which inversely correlated with bone mineral content and bone mineral density measures, suggesting macrophage activation as a possible mechanism of differential bone loss.

Vitamin D deficiency and insufficiency occur frequently in youth with HIV infection, particularly among those receiving the antiretroviral drug efavirenz. Optimal vitamin D dosing for treatment is unclear.Our objective was to evaluate safety and measure change in 25-hydroxyvitamin D (25-OHD) concentration from baseline to study wk 4 and 12 during treatment with vitamin D(3), 50,000 IU monthly.We conducted a randomized double-blind, placebo-controlled multicenter trial of HIV-infected youth ages 18-24 yr, with viral load below 5000 copies/ml, on stable antiretroviral therapy.INTERVENTION included vitamin D(3), 50,000 IU (n = 102), or matching placebo (n = 101) administered in three directly observed oral doses at monthly intervals.At baseline, mean (sd) age was 20.9 (2.0) yr; 37% were female and 52% African-American, and 54% were vitamin D deficient/insufficient (25-OHD20 ng/ml), with no randomized group differences. Of evaluable participants vitamin D deficient/insufficient at baseline who were administered vitamin D, 43 of 46 (93%) had sufficient 25-OHD by wk 12. Vitamin D supplementation increased 25-OHD serum concentration from a baseline of 21.9 (13.3) to 35.9 (19.1) ng/ml at wk 12 (P0.001) with no change for placebo. Although use of the antiretroviral efavirenz was associated with lower baseline 25-OHD concentration, efavirenz did not diminish the response to vitamin D supplementation. There was no treatment-related toxicity.Supplementation with vitamin D(3) 50,000 IU monthly for three doses was safe. Increases in 25-OHD occurred in treated participants regardless of antiretroviral regimen.

BackgroundMost studies of the mental health of UK armed forces focus on retrospective accounts of deployment and few sample personnel while they are deployed.AimsThis study reports the results of a survey of deployed personnel, examining the perceived impact of events at home and military support for the family on current mental health during the deployment.MethodSurveys were conducted with 2042 British forces personnel serving in Iraq and Afghanistan. Prevalence of common mental disorders was assessed with the 12-item General Health Questionnaire (GHQ-12) and post-traumatic stress disorder (PTSD) was assessed with the PTSD Checklist – Civilian version (PCL-C).ResultsThe prevalence of common mental disorders was 17.8% and of probable PTSD was 2.8%. Perceived home difficulties significantly influenced the mental health of deployed personnel; the greater the perception of negative events in the home environment, the greater the reporting of adverse mental health effects. This finding was independent of combat exposure and was only partially mitigated by being well led and reporting subjectively good unit cohesion; however, the effect of the totality of home-front events was not improved by the latter. Poor perceived military support for the family had a detrimental impact on deployment mental health.ConclusionsThe armed forces offer many support services to the partners and families of deployed personnel and ensuring that the efforts being made on their behalf are well communicated might improve the mental health of deployed personnel.

Peak bone mass is achieved in adolescence/early adulthood and is the key determinant of bone mass in adulthood. We evaluated the association of bone mass with human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) during this critical period among behaviorally HIV-infected young men and seronegative controls.HIV-positive men (N = 199) and HIV-negative controls (N = 53), ages 14-25 years, were studied at 15 Adolescent Trials Network for HIV/AIDS Interventions sites. HIV-positive participants were recruited on the basis of ART status: ART-naive (N = 105) or on a regimen containing a nonnucleoside reverse transcriptase inhibitor (NNRTI; N = 52) or protease inhibitor (PI; N = 42). Bone mineral density (BMD) and content (BMC) and body composition were measured by dual-energy X-ray absorptiometry (DXA). Results were compared across groups by linear modeling. Bone results were adjusted for race, body mass index (BMI), and type of DXA (Hologic/Lunar).The HIV-positive and HIV-negative groups had comparable median age (21 years) and racial/ethnic distribution. Median times since HIV diagnosis were 1.3, 1.9, and 2.2 years in the ART-naive, NNRTI, and PI groups, respectively (P = .01). Total and regional fat were significantly lower in the ART-naive group compared with seronegative controls. Mean BMD and Z scores were generally lower among HIV-positive participants on ART, particularly in the PI group. Average Z scores for the spine were below zero in all 4 groups, including controls.Young men on ART with a relatively recent diagnosis of HIV infection have lower bone mass than controls. Longitudinal studies are required to determine the impact of impaired accrual or actual loss of bone during adolescence on subsequent fracture risk.

Armed Forces personnel who deploy as individual augmentees (IAs), with a unit other than their formed unit, often fill shortages or provide specialized knowledge or skill sets. This article examined the effect of deploying as an IA on mental health outcomes and unit cohesion. A U.K. military cohort study was used to compare IAs (n = 1352) with personnel who had deployed with a formed unit (n = 2980). Differences between the groups in questionnaire assessed symptoms of post-traumatic stress disorder (PTSD Checklist-Civilian Version), common mental disorders (General Health Questionnaire-12) and alcohol misuse (Alcohol Use Disorders Identification Test) were examined with logistic and negative-binomial regression analyses. There was no difference between IAs and those who deployed with a formed unit in level of unit cohesion, symptoms of post-traumatic stress disorder or common mental disorder. Deployment as an IA was associated with less alcohol misuse (Odds Ratio 0.77, 95% Confidence Interval 0.63-0.94). IAs appeared able to integrate with the group they deployed with as levels of unit cohesion were similar to personnel who deployed with a formed unit. IAs were also at a lower risk of alcohol misuse compared to personnel who deployed with a formed unit.

Cluster heat maps were used to investigate relationships between body composition, lipid levels, and glucose metabolism in HIV-infected and HIV-uninfected children and young adults using data from a cross-sectional study. Three distinct clusters of participants were identified. One group had lower body fat and higher lipid measures and was mostly HIV infected. The other 2 groups were a mix of HIV-infected and HIV-uninfected participants. Of these, 1 cluster had more participants with higher body fat and insulin resistance, which are risk factors for future cardiovascular disease, and the other had relatively normal measurements on all outcomes.

Background: Total body volume (TBV), with the exclusion of internal air voids, is necessary to quantify body composition in Lohman's 4-compartment (4C) model. Objective: This investigation sought to derive a novel, TBV measure with the use of only dual-energy X-ray absorptiometry (DXA) attenuation values for use in Lohman's 4C body composition model. Design: Pixel-specific masses and volumes were calculated from low- and high-energy attenuation values with the use of first principle conversions of mass attenuation coefficients. Pixel masses and volumes were summed to derive body mass and total body volume. As proof of concept, 11 participants were recruited to have 4C measures taken: DXA, air-displacement plethysmography (ADP), and total body water (TBW). TBV measures with the use of only DXA (DXA-volume) and ADP-volume measures were compared for each participant. To see how body composition estimates were affected by these 2 methods, we used Lohman's 4C model to quantify percentage fat measures for each participant and compared them with conventional DXA measures. Results: DXA-volume and ADP-volume measures were highly correlated (R2 = 0.99) and showed no statistically significant bias. Percentage fat by DXA volume was highly correlated with ADP-volume percentage fat measures and DXA software-reported percentage fat measures (R2 = 0.96 and R2 = 0.98, respectively) but were slightly biased. Conclusions: A novel method to calculate TBV with the use of a clinical DXA system was developed, compared against ADP as proof of principle, and used in Lohman's 4C body composition model. The DXA-volume approach eliminates many of the inherent inaccuracies associated with displacement measures for volume and, if validated in larger groups of participants, would simplify the acquisition of 4C body composition to a single DXA scan and TBW measure.

Background: Children and young people (CYP) with juvenile idiopathic arthritis (JIA) are known to have impaired health-related quality of life (HRQoL), which is improved significantly for many by treatment with methotrexate (MTX). However, a significant proportion of CYP experience difficulties in taking MTX, which may reduce its potential benefits for HRQoL. The aim of this research was to examine how CYP with JIA perceive MTX treatment and how this relates to HRQoL.\ud \ud Methods: CYP aged 8-16 years taking MTX for JIA completed an adapted Parent Adherence Report Questionnaire, which contains 100mm visual analogue scales, to assess difficulty taking MTX, adherence, frequency of negative reactions and helpfulness of MTX. They also completed the Pediatric Quality of Life Inventory (PedsQL) Generic and Rheumatology scales. We collected data on age, gender, JIA course, disease duration, MTX duration of use, route and dose. Number of inflamed and limited joints were indicators of disease severity.\ud \ud Results: 116 CYP participated. Most considered MTX helpful (median 87; interquartile range (IQR) 50.75–98) and reported adherence was high (median 98; IQR 90–100). There was greater variability on scores for difficulty (median 22; IQR 2–69) and frequency of negative reactions (median 14.5; IQR 1.25–80). Mean (S.D.) scores on the PedsQL Physical and Psychosocial subscales were 71.63 (24.02) and 71.78 (19.59) respectively, indicating poorer HRQoL than that reported by healthy children. After controlling for demographic and disease variables, poorer physical HRQoL was significantly accounted for by greater difficulty in taking MTX. Poorer psychosocial HRQoL was significantly accounted for by subcutaneous MTX administration, a lower rating of MTX helpfulness and a greater reported difficulty in taking MTX.\ud \ud Conclusions: Taking MTX for JIA was viewed as helpful by most CYP but HRQoL was poorer in those who reported greater difficulty in taking MTX.

The HIV pandemic continues to place an unbearable burden on the international community, with disease prevalence remaining highest in resource-limited settings in Africa, Asia, and the Americas. HIV is most often imposed on conditions of food insecurity and consequent malnutrition, poor sanitation, and chronic exposure to a myriad of infectious (eg, malaria, tuberculosis, and diarrheal) and noncommunicable (eg, obesity, diabetes, cancer, and cardiovascular) diseases. Women and children continue to bear the greatest burden. Two essential tenets underpin our approach to HIV: 1) antiretroviral drugs (ARVs) are essential to prolong lives and to halt the spread of HIV and AIDS and 2) food and sound nutrition are essential to human health. The challenge is to apply sound principles of clinical care and nutrition science to the safe and efficacious implementation of ARVs and for long-term care for people living with HIV and AIDS. The WHO has played a leading role in developing guidelines to support this goal with the generation of general recommendations regarding nutritional needs of people living with HIV and AIDS and specific guidelines for the nutritional care of HIV-infected infants and children (

Objectives. This study sought to examine how patients’ mood and quality of life (QoL) change during the early high-risk period after a diagnosis of heart failure (HF) and to identify factors that may influence change. Design. A within-subjects, repeated-measures design was used. Assessments took place within 4 weeks of diagnosis and 6 months later. Methods. One hundred and sixty six patients with HF completed assessments of their mood, QoL, and beliefs about HF and its treatment. Correlation analysis was conducted between the variables and analysis of variance and t-tests were used to assess differences in categorical variables. To examine which variables predicted mood and QoL, hierarchical multiple regressions were conducted. Results. At follow-up, patients’ beliefs indicated a realization of the chronicity of their HF, however their beliefs about the consequences of having HF did not change and their satisfaction with their treatment remained high. QoL and anxiety improved significantly over time but there was no significant change in depressed mood. As would be expected, improvement in symptoms was a key factor in improved mood and QoL. Other significant explanatory variables included age, comorbid chronic obstructive pulmonary disease, depressed mood, patients’ beliefs about the consequences of their HF and their concerns about treatment. Conclusions. This study suggests that addressing patients’ mood and beliefs about their illness and its treatment may be additional ways of improving patient QoL in the early period after the diagnosis of HF.

There is now an abundance of research which has demonstrated that military personnel who deploy on operations are at increased risk of suffering a variety of mental health diffi culties in the immediate and long-term post-deployment period. One consequence of these research fi ndings has been the development of a variety of programmes which attempt to mitigate the increased psychological risk and to assist personnel who are returning from a deployment to make a smooth transition home. Using a three-tiered prevention model, this article reviews some of the key post-deployment issues facing the UK Armed Forces and highlights the recent interventions which have been put in place to promote successful adjustment in the early post-deployment period. The paper is based upon research identifi ed through a thorough literature search for studies which focused on this area and included a recognized measure of mental health as an outcome. The paper focuses on three main areas; psychological decompression, psycho-education and screening. The current philosophical approaches to post-deployment mental health problems of some of the UK ’ s coalition partners are also discussed.

The Society for Sarcopenia, Cachexia, and Wasting Disease convened an expert panel to develop nutritional recommendations for prevention and management of sarcopenia. Exercise (both resistance and aerobic) in combination with adequate protein and energy intake is the key component of the prevention and management of sarcopenia. Adequate protein supplementation alone only slows loss of muscle mass. Adequate protein intake (leucine-enriched balanced amino acids and possibly creatine) may enhance muscle strength. Low 25(OH) vitamin D levels require vitamin D replacement.

The purpose of this study was to examine self-management and educational interventions developed to support people with inflammatory bowel disease (IBD) and to identify which type of intervention seems to be most effective. The search was deliberately overinclusive to capture studies that evaluated educational and self-management interventions. The following databases were searched: MEDLINE, Embase, CINAHL, PsycINFO, the National Research Register, and Cochrane. Twenty-three studies were included. Thirteen of these were randomized controlled trials. The content of the interventions reviewed varied widely. As expected, it is the three studies that have explicitly labeled themselves as self-management interventions that have incorporated the greatest number of self-management techniques. Two of these studies reported the greatest number of improved outcomes in relation to symptom reporting, psychological well-being, and healthcare resource use. There is clearly a role for information in IBD, but this review supports research in other conditions that shows that education cannot be assumed to lead to improvements in health and well-being. Much of the research in this area focuses on education rather than self-management. Where self-management techniques have been applied, the findings tend to be more promising. Gastroenterology nurses (or in the United Kingdom, IBD specialist nurses) may be best placed to facilitate self-management in this group.

Background. The goal of this study was to determine the nature and prevalence of abnormalities in lipids, glucose metabolism, and body composition in behaviorally human immunodeficiency virus (HIV)―infected young women and the relationship of these abnormalities to different classes of antiretroviral therapy regimens. Methods. We conducted a cross-sectional, multicenter study involving 173 behaviorally HIV-infected women aged 14-24 years and 61 HIV-seronegative control subjects. HIV-infected women were categorized as follows: antiretroviral therapy naive (n = 85), receiving a regimen containing a nonnucleoside reverse-transcriptase inhibitor (NNRTI; n = 33), receiving a regimen containing a protease inhibitor (PI; n = 36), or receiving a regimen not containing an NNRTI or a PI (n = 19). Measurements included fasting lipid levels, glucose and insulin levels before and 2 hours after an oral glucose challenge, high-sensitivity C-reactive protein (hsCRP) levels, anthropometry, fat distribution (measured by dual energy X-ray absorptiometry), and antiretroviral therapy and medical histories. Race-adjusted results were compared across groups and within HIV-infected groups. Results. The median age of participants was 20 years. Of HIV-infected subjects, 77% were African American, 35% smoked cigarettes, and 32% reported exercising regularly. More than 40% had a body mass index ≥25. Triglycerides; total, high-density lipoprotein (HDL), and non-HDL cholesterol; and hsCRP levels differed significantly among groups, with higher levels being most common among those receiving antiretroviral therapy. Indices of glucose metabolism did not differ among groups. In general, cholesterol levels, hsCRP levels, and indices of glucose metabolism worsened as body mass index increased. Conclusions. Obesity, dyslipidemia, and inflammation were prominent among HIV-infected adolescent women and, coupled with other risk factors, may accelerate the lifetime risk of cardiovascular disease and other adverse events. These results underscore the need for a multifaceted approach to addressing risk reduction in this population.

BACKGROUND HIV protease inhibitors have been shown to worsen glucose and lipid metabolism. Recent studies have suggested that protease inhibitors can impair insulin secretion in HIV-infected patients. We studied the effects of the protease inhibitor combination lopinavir and ritonavir on insulin secretion, insulin sensitivity, and lipid metabolism in HIV-negative persons. METHODS A combination dose of lopinavir 400 mg and ritonavir 100 mg was given twice daily to eight HIV-seronegative men for 4 weeks. Fasting glucose, insulin, lipid, and lipoprotein profiles; oral glucose tolerance; insulin secretion and insulin-mediated glucose disposal by hyperglycemic clamp; and body composition by dual energy X-ray absorptiometry were determined before and after lopinavir/ritonavir administration. RESULTS There was no change in first-phase insulin secretion (2.82 +/- 0.30 versus 2.71 +/- 0.31 nmol/l; P = 0.60), as well as fasting insulin and glucose levels, oral glucose tolerance, or insulin-mediated glucose disposal after 4 weeks administration of lopinavir/ritonavir. However, there were significant increases in fasting triglycerides (1.02 +/- 0.13 versus 2.20 +/- 0.31 mmol/l; P = 0.001), total cholesterol (4.42 +/- 0.30 versus 5.70 +/- 0.60 mmol/l; P = 0.007), and apo B-100 levels (0.86 +/- 0.07 versus 1.07 +/- 0.11 g/l; P = 0.0009). High-density lipoprotein cholesterol decreased (0.99 +/- 0.11 versus 0.82 +/- 0.10 mmol/l; P = 0.005). There were no changes in body composition, weight, or body fat. CONCLUSION Although administration of lopinavir/ritonavir to healthy, HIV-seronegative volunteers for 4 weeks resulted in increased triglyceride and decreased high-density lipoprotein cholesterol levels, there was no change in first-phase insulin secretion during the hyperglycemic clamp. The reported effects of protease inhibitor on insulin secretion in HIV-infected individuals may be due to changes in HIV-related factors and not a direct drug effect.

To compare the distribution of lipid and glucose abnormalities and altered fat distribution among vertically HIV-infected patients and controls.Cross-sectional multicenter study on HIV-infected (HIV-positive) patients, 7-24 years of age, stratified by Tanner stage and protease inhibitor use (protease inhibitor, n = 161 and non- protease inhibitor, n = 79) and seronegative controls (HIV-negative, n = 146).Measurements included fasting lipids, glucose, insulin, 2-h oral glucose tolerance test, dual-energy X-ray absorptiometry, anthropometry, and antiretroviral therapy and medical histories. Multiple linear regression models were used to compare distributions between HIV-positive and HIV-negative groups.Both HIV-positive groups had long exposures to antiretroviral therapy. Protease inhibitor and nonprotease inhibitor groups had similar current CD4 cell count and HIV-1 RNA, but the protease inhibitor group had lower nadir CD4 cell count, higher peak HIV-1 RNA, and more advanced Centers for Disease Control disease stage. In adjusted analyses, both HIV-positive groups had significantly lower mean Z scores for height, weight, BMI, and total and limb fat than the HIV-negative group. Mean triglycerides were significantly higher and high-density lipoprotein cholesterol lower in both HIV-positive groups relative to the HIV-negative group. The protease inhibitor group also had significantly higher mean total, low-density lipoprotein, and non-high density lipoprotein cholesterol. Mean fasting insulin was higher in both HIV-positive groups, and 2-h glucose and insulin were higher in the protease inhibitor group. Ritonavir was associated with increasing dyslipidemia and altered glucose metabolism.In a large group of vertically HIV-infected children and youth with extensive antiretroviral therapy exposure, height, weight, and total and limb fat were lower than in controls. There was a high prevalence of lipid abnormalities among those on protease inhibitors and evidence of developing insulin resistance, factors that may accelerate lifetime risk for cardiovascular disease.

To assess the prevalence of metabolic syndrome (MetSynd) among participants of the Women's Interagency HIV Study and to describe the association of MetSynd with HIV infection, antiretroviral therapies, and sociodemographic factors.Prevalence of MetSynd, defined by updated Adult Treatment Panel III guidelines, was assessed among 2393 (1725 seropositive and 668 seronegative) participants from the Women's Interagency HIV Study seen between October 2000 and October 2004.HIV-1 infection was independently associated with MetSynd [33% vs 22%, P0.0001 in HIV-seropositive compared with HIV-seronegative women; adjusted odds ratio (OR) 1.79 (95% confidence interval 1.48, 2.16)]. HIV-infected women had higher mean triglyceride (154 vs 101 mg/dL, P0.0001) and lower mean high-density lipoprotein cholesterol levels (46 vs 55 mg/dL, P0.0001). Most notable factors associated with higher prevalence of MetSynd among HIV-infected women included older age (OR=1.38 per 5 year increase, P0.0001); higher body mass index; current smoking; HIV-1 RNA (OR=1.36, P=0.019, for50,000 vs80 copies/mL); and use of stavudine (OR=1.28, P=0.009). Nevirapine use was protective (OR=0.75, P=0.016). There was no significant association of MetSynd with ritonavir-boosted protease inhibitors (OR=1.15, P=0.134).MetSynd is more prevalent in HIV-seropositive than HIV-seronegative women. This increased prevalence was due to dyslipidemias rather than higher blood pressure, glucose, or waist circumference.

Background Low bone mineral density (BMD) has been reported in HIV-infected women and men. Methods We analysed cross-sectional BMD measured by regional dual X-ray absorptiometry at the lumbar spine (LS) and femoral neck (FN) in 152 HIV-negative and 274 HIV-positive (HIV+) women, adjusted for traditional low BMD risk factors. Results BMD was significantly lower in protease inhibitor (PI) users than in all other groups, and highest in HIV-negative women. In multivariate analyses the prevalence of T-score + women naive to antiretroviral therapy (ART; odds ratio [OR] 4.36, 95% confidence interval [CI] 1.61, 11.8) and the women receiving PI-containing HAART (OR 3.72, CI 1.43, 9.68), with a non-significant difference in non-PI HAART users (OR 2.43, CI 0.92, 6.45), compared with HIV-negative women. In pair-wise adjusted comparisons, BMD was lower in ART-naive than in HIV-negative women (1.22 versus 1.30 g/cm2 at LS; P=0.004), in PI compared with non-PI HAART users (1.00 versus 1.05 g/cm2 at FN; P=0.014) and with those ART-naive (1.00 versus 1.03 g/cm2 at FN; P=0.146). Potential confounders, including duration of ART, prior treatment regimens and traditional risk factors for low BMD did not explain these differences. Longer lopinavir use was significantly correlated with lower BMD (r2=-0.39, P=0.024 and r2=-0.46, P=0.006 at LS and FN, respectively) and longer efavirenz use with higher BMD (r2=+0.32, P=0.004 at FN). Conclusions HIV infection was associated with lower BMD in women, independent of the traditional risk factors for low BMD. PI-containing HAART compared with non-PI-containing HAART, and longer lopinavir use, were both associated with lower BMD, and efavirenz use was associated with higher BMD.

Background: Long-term regional body fat outcomes have not been well described in randomized antiretroviral drug trials. Methods: Dual x-ray absorptiometry (DXA) scans were performed every 16 weeks on a subset of 157 antiretroviral-naive participants who were randomized to receive nelfinavir, efavirenz, or both, combined with zidovudine and lamivudine or stavudine and didanosine, in a multicenter trial. Participants with any available data after baseline up to week 144 contributed to this as-treated analysis. Results: Limb fat increased similarly in all groups during the first 32 weeks. After week 32, limb fat changed by -1.7% per year for zidovudine-lamivudine and by -19.0% per year for didanosine-stavudine (mixed model analysis of variance [MMANOVA], P < 0.0001). Adjusting for nucleoside backbone, there was an additional decrease in limb fat of -8.7% per year for the combined nelfinavir and nelfinavir + efavirenz group compared with the efavirenz group (MMANOVA, P = 0.03). Among participants receiving zidovudine-lamivudine, after week 32, limb fat changed by +2.7% per year with efavirenz and by -7.9% per year for the combined nelfinavir and nelfinavir + efavirenz group (MMANOVA, P = 0.03). Conclusions: Over 144 weeks, zidovudine-lamivudine was superior to didanosine-stavudine with regard to limb fat loss. The combination of zidovudine, lamivudine, and efavirenz showed no overall pattern suggesting limb fat loss over time and was significantly superior to the pooled zidovudine-lamivudine-nelfinavir (with and without efavirenz) arms.

Reduced energy intake is a primary factor in HIV-associated wasting. Megestrol acetate (MA) stimulates appetite and weight gain. However, much of the weight gained is fat, possibly as a result of MA-induced hypogonadism.The objective of the study was to determine whether coadministration of testosterone with MA could enhance lean body mass (LBM) accrual and evaluate the effects of MA, alone or combined with testosterone, on sexual functioning and the hypothalamic-pituitary-adrenal axis.This was a randomized, double-blind, placebo-controlled, multicenter trial.Fourteen AIDS Clinical Trials Units in the United States participated in the study.Seventy-nine HIV-positive men with 5% or more weight loss or body mass index less than 20 kg/m2 took part in the study.Subjects were randomized to receive MA (800 mg daily) plus testosterone enanthate (200 mg; MA/TE; n = 41) or placebo (MA/PL; n = 38) biweekly for 12 wk.Weight, body composition (bioelectric impedance analysis), adrenal and gonadal hormones, and sexual functioning (questionnaire) were measured.Both groups experienced robust increases in weight (median 5.3 and 7.3 kg in MA/TE and MA/PL, respectively), LBM (3.3 and 3.3 kg), and fat (3.0 and 3.8 kg). There were no significant differences between groups in the magnitude or composition of weight gain (P = 0.44, 0.90, and 0.11 for weight, LBM, and fat, respectively). Trough testosterone concentrations decreased to a greater extent in MA/PL (-12.3 vs. -6.1 nmol/liter in MA/TE; P = 0.04). Cortisol levels became nearly undetectable in subjects with plasma MA levels greater than 150 ng/ml. Sexual functioning was preserved with MA/TE but worsened in MA/PL.MA produced robust weight gain. Coadministration of testosterone preserved sexual functioning but did not enhance LBM accrual.

OBJECTIVE To evaluate the effects of metformin and rosiglitazone, alone or in combination, on fat distribution, insulin sensitivity, and lipids in HIV-infected patients with insulin resistance and changes in fat distribution. METHODS A total of 105 subjects were randomly assigned to receive metformin (500 mg twice a day increasing to 1000 mg twice a day after 2 weeks) with rosiglitazone placebo (Met/P, N = 26); rosiglitazone (4 mg/day) with metformin placebo (Rosi/P, N = 27); rosiglitazone (4 mg/day) plus metformin (500 mg twice a day increasing to 1000 mg twice a day after 2 weeks; Met/Rosi, N = 25); or dual placebo (P/P, N = 27) for 16 weeks. Efficacy assessments included oral glucose tolerance testing, abdominal computed tomography, whole-body dual-energy X-ray absorptiometry, and the measurement of fasting lipids and other biochemical indices. Safety was monitored throughout. Intent-to-treat analyses were performed using non-parametric methods. RESULTS The median insulin area under the curve (AUC) decreased significantly compared with baseline in both groups randomly assigned to rosiglitazone (Rosi/P -25.7 microIU/ml, P = 0.012; Met/Rosi -17.7 microIU/ml, P = 0.002); and tended to decrease in the Met/P group (-11.1 microIU/ml, P = 0.058). The change in AUC with combination therapy was significant compared with placebo (P = 0.032). No treatment was associated with significant changes in visceral or subcutaneous abdominal fat. Leg fat increased in subjects on Rosi/P compared with placebo (+4.8 versus -8.3%, P = 0.034). Rosiglitazone, but not metformin, increased adiponectin but also increased LDL-cholesterol and decreased HDL-cholesterol. Gastrointestinal effects occurred frequently in subjects on metformin. CONCLUSION Both treatments improved insulin sensitivity, but neither reduced visceral fat. Rosiglitazone may increase subcutaneous fat in some individuals.

Introduction: Although peripheral fat loss is a consistent feature of HIV-associated lipodystrophy, less is known about whether changes in central and peripheral fat occur in tandem or independently over time. We examined intraindividual changes in dual-energy x-ray absorptiometry (DEXA) and anthropometry data over 64 weeks after initiation of antiretroviral therapy (ART). Methods: In ACTG 384, ART-naive subjects were randomized to receive didanosine and stavudine or zidovudine and lamivudine plus efavirenz, nelfinavir, or both. In the metabolic substudy A5005S (N = 329), waist, hip, thigh, and arm circumferences were measured in triplicate. DEXA scanning was performed in 157 subjects. Results: Individual changes in limb and trunk fat at week 64 correlated positively (R = .72, P

Objective: To determine if particular components of antiretroviral drug regimens are associated with greater insulin resistance, dyslipidemia, and peripheral lipoatrophy. Methods: Metabolic and body composition variables were measured prospectively over 64 weeks in 334 antiretroviral-naive, HIV-infected subjects who were randomized to receive nelfinavir, efavirenz, or both, combined with zidovudine/lamivudine or didanosine/stavudine in a factorial design, multicenter trial. Subjects assigned to efavirenz (n = 110) were compared with those assigned to nelfinavir (n = 99); subjects assigned to zidovudine/lamivudine (n = 154) were compared with those assigned to didanosine/stavudine (n = 180). A subset of 157 subjects had serial dual-energy X-ray absorptiometry (DEXA) scans. Results: Lipid measures increased in all groups. Greater increases in high density lipoprotein (HDL) cholesterol occurred with efavirenz than with nelfinavir. Greater increases in total cholesterol, non-HDL cholesterol and HDL cholesterol occurred with stavudine and didanosine than with zidovudine/lamivudine. There were no differences in insulin resistance in the comparisons. After initial increases in the first 16 weeks, median limb fat decreased. Greater changes in percentage changes in limb fat occurred with didanosine/stavudine (-16.8%) than with zidovudine/lamivudine (+4.0%; P < 0.001 for overall change from baseline) and with nelfinavir (-13.1%) compared with efavirenz (+1.8%; P = 0.003). Conclusions: Over 64 weeks, all regimens were associated with increases in lipids but insulin resistance did not differ between groups. Regimens containing didanosine/ stavudine and regimens containing nelfinavir were associated with greater loss of limb fat.

Few studies have prospectively evaluated the impact of highly active antiretroviral therapy (HAART) on body weight and lean body mass (LBM) or explored the impact of baseline immunologic or virological changes on these parameters.Adult AIDS Clinical Trials Group (ACTG) protocol 892 was a prospective, 48-week, multisite observational study of body composition conducted during 1997-2000 among 224 antiretroviral-naive and antiretroviral-experienced subjects coenrolled into various adult ACTG antiretroviral studies. Assessments included human immunodeficiency virus type 1 (HIV-1) RNA load (by polymerase chain reaction); T lymphocyte subset analysis; Karnofsky score; height (baseline only); weight, LBM, and fat (by bioelectrical impedance analysis); and functional performance (by questionnaire).Overall, only modest median increases in body weight (1.9 kg) and LBM (0.6 kg) occurred after 16 weeks of therapy. Significantly greater median increases in body weight (2.1 vs. 0.5 kg; P=.045) occurred in subjects who achieved virological suppression (HIV-1 RNA load,500 copies/mL) at week 16 than in subjects who did not. Subjects who were antiretroviral naive at baseline gained more weight (median increase in body weight, 2.6 vs. 0.0 kg; P.001) and LBM (1.0 vs. 0.1 kg; P=.002) after 16 weeks of treatment than did subjects who were antiretroviral experienced. Subjects with lower baseline CD4 cell counts (200 cells/mm3) and subjects with higher baseline HIV-1 RNA loads (or =100,000 copies/mL) were more likely to show increases in LBM of1.5 kg (P=.013 and P=.005, respectively).HAART had modestly favorable effects on body composition, particularly in patients with greater pretreatment immunocompromise and virological compromise. The difference between antiretroviral-naive and antiretroviral-experienced subjects with regard to the ability to achieve increased body weight and LBM requires more study.