OBJECTIVES:High rates of respiratory symptoms and chronic bronchitis (CB) are reported in people with HIV infection (PWH). We investigated the prevalence of respiratory symptoms and CB in PWH and HIV-negative people in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) study.METHODS:Assessment of respiratory symptoms and CB was undertaken using the modified form of the St. George's Respiratory Questionnaire for chronic obstructive pulmonary disease (COPD). Univariate (χ2 tests, Mann-Whitney U tests and Spearman's rank correlation) and multivariable (linear and logistic regression) analyses were performed to consider associations of respiratory symptoms with demographic, lifestyle and HIV-related parameters, and with depressive symptoms and quality of life.RESULTS:Among the 619 participants, respiratory Symptom scores were higher in older and younger PWH compared to older HIV-negative people, with median (interquartile range) scores of 17.7 (6.2, 39.5), 17.5 (0.9, 30.0) and 9.0 (0.9, 17.5), respectively (P = 0.0001); these differences remained significant after confounder adjustment. Sixty-three participants (10.2%) met the criteria for CB [44 (14.0%) older PWH, 14 (9.2%) younger PWH, and five (3.3%) older HIV-negative people; P = 0.002], with these differences also remaining after adjustment for confounding variables, particularly smoking status [older vs. younger PWH: odds ratio (OR) 4.48 (95% confidence interval (CI) 1.64, 12.30); P = 0.004; older PWH vs. HIV-negative people: OR 4.53 (95% CI 1.12, 18.28); P = 0.03]. Respiratory symptoms and CB were both associated with greater depressive symptom scores and poorer quality of life. No strong associations were reported between CB and immune function, HIV RNA or previous diagnosis of any AIDS event.CONCLUSIONS:Respiratory symptoms and CB are more common in PWH than in demographically and lifestyle-similar HIV-negative people and are associated with poorer mental health and quality of life.

Objectives: The aims of the study were to describe the prevalence of obesity in the POPPY cohort, to identify demographic, clinical and HIV-specific factors associated with obesity, and to characterize the association between obesity and socio-demographic, clinical, HIV-specific factors and quality-oflife (QoL). Methods: Cross-sectional analysis of baseline data from the three groups (“older” people with HIV (PWH) aged ≥50 years, “younger” PWH aged <50 years, HIV-negative controls aged ≥50 years) within the POPPY cohort. Obesity was defined as a Body Mass Index (BMI) > 30 Kg/m. Results: 1361 subjects were included, of which 335 (24.6%) were obese. The prevalence of obesity was higher in controls (22.3%) than in older (16.8%) and younger (14.2%) PWH, with no differences between the two groups of PWH. Factors associated with obesity were older age, female gender, black African ethnicity and alcohol consumption. Recreational drug use and a higher current CD4+ T-cell count (in PWH) were associated with lower and higher odds of being obese, respectively. Presence of obesity was associated with worse physical health QoL scores, higher odds of having cardiovascular disease, type 2 diabetes, hypertension but lower odds of having osteopenia/osteoporosis, irrespective of HIV status. Conclusions: Despite a lower prevalence of obesity in PWH, specific subgroups (women, people of black African origin and older people) were more likely to be obese and negative health consequences of obesity were evident, regardless of HIV status. Whether targeted preventive strategies can reduce the burden of obesity and its complications in PWH remains to be determined. Introduction Obesity represents an emerging health problem worldwide. According to the World Health Organization (WHO) 39% of women and men globally were overweight in 2016, with the prevalence of obesity nearly tripling since 1975 [1]. The prevalence of being overweight, defined as a body mass index (BMI) ≥25 kg/m, is particularly high in developed countries, with prevalence rates in Ireland and the UK among the highest (>60%) in Europe. Obesity (defined as a BMI ≥30 kg/m) is associated with increased all-cause and cardiovascular disease (CVD) mortality in the general population, especially in severely obese subjects (BMI ≥35 kg/m) [2]. Antiretroviral therapy (ART) has transformed HIV into a chronic condition with life expectancy of people with HIV (PWH) approaching that of the general population [3]. However, there has been a concomitant increase in non-AIDS related co-morbidities such as CVD and metabolic complications, related to a number of factors, including ageing and immune activation [4]. Moreover, the prevalence of obesity in PWH, including those from low-income countries, is rising [5-12] and several studies have tried to identify risk factors for obesity in this population. While most of the findings from observational studies agree on the existence of associations between obesity and older age, female gender and length of HIV infection [6-9,11,12], reported associations with CD4 T-cell count and different antiretroviral (ARV) regimens are controversial [6-9,12-17] and few studies have explored associations between ageing and obesity in PWH with appropriate control groups. The Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) Study is a multicentre, prospective, observational study initiated in 2013 to assess the clinical outcomes of PWH over the age of 50 in England and Ireland [18]. Given evidence suggesting an accentuated and perhaps accelerated ageing process in PWH [19], the POPPY study aims to describe the burden of clinical conditions in older PWH compared with two demographically similar control groups; younger PWH and older HIV-negative individuals. This cohort provides an opportunity to examine the risk factors for obesity and associated conditions in both PWH and HIV negative subjects that can explore the impact of ageing. The aims of our study were to describe the prevalence of obesity in the POPPY cohort, and to define the associations of demographic, clinical and HIV-specific factors with obesity. These data may help identify potential targets for future research into prevention strategies to avoid the development of obesity and its complications. Methods Study design and participants The characteristics of the POPPY cohort and the eligibility criteria have been described previously [18]. The cohort includes three groups of people: “older” PWH aged ≥50 years, “younger” PWH aged <50 years and HIV-negative controls aged ≥50 years. All subjects were either of white or black African ethnicity and PWH had a history of sexually acquired HIV infection (those with intravenous drug use as a principal transmission risk factor were not included). The younger PWH were frequency-matched with the older PWH in terms of gender, ethnicity, sexual orientation and participating clinic, whereas the HIV-negative controls were frequency-matched with the older PWH on gender, ethnicity, sexual orientation and location, and were recruited in sexual health clinics or through community recruitment strategies. All participants provided written informed consent. The present study is a cross-sectional analysis based on information collected at cohort enrollment (April 2013-February 2016) including only those subjects with available data on BMI. Data collection. Demographic, socio-economic and clinical information was collected by trained staff using a structured questionnaire, as previously described [20]. Weight and height were measured at the baseline visit, following a standardised protocol across clinical sites. Obesity was defined as a BMI ≥30 kg/m, based on the WHO case definition. A history of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection was defined on the basis of available serological tests or clinical records; information on other medical conditions was reported by the subjects during the interview, including CVD, type 2 diabetes, renal disease, liver disease and hypertension. Co-morbidities were confirmed with the aid of medical notes, healthcare resources use records and list of medications. Osteopenia and osteoporosis were defined as a T-score between -1.0 and -2.5 and a T-score <-2.5, respectively, as assessed with Dual-energy X-ray Absorptiometry (DXA) measuring bone mineral density (BMD) at the lumbar spine and the hip. For each study participant quality of life was assessed during the visit using the Short Form 36 (SF-36) questionnaire [21]. HIV-specific parameters (prior AIDS events, dates and values of all CD4 and CD8 T-cell counts and HIV RNA assessments, and a detailed ART history) were derived through linkage with the UK CHIC study and the University College Dublin Infectious Diseases (UCD ID) cohort for subjects recruited in the Republic of Ireland [22,23]. Statistical analysis Median and interquartile range (IQR) or frequency were used to describe the characteristics of the study participants as appropriate. Overall differences in the prevalence of obesity between the groups were tested for significance using the Chi-squared test. In order to identify factors associated with obesity in the full study population, a logistic regression analysis was performed, using obesity as the dependent variable and demographic (gender, ethnicity, mode of HIV acquisition/sexual orientation, marital status, educational attainment), lifestyle (smoking status, alcohol consumption, recreational drug use in the past 6 months) and clinical factors (HBV and/or HCV coinfection, number of medications received, use of lipid-lowering drugs (LLD), mental health medications or corticosteroids) as independent variables. For the purposes of these analyses, the two groups of PWH were combined to allow for HIV status and age to be considered as separate factors. Those variables for which an association with obesity was observed in univariable analysis (with p<0.1 used as a threshold for significance), were included simultaneously in a multivariable regression model (multivariable analysis 1). HIV status, age, gender and ethnicity were retained in the model irrespective of their level of significance, considering their supposed importance as factors associated with obesity from previous studies [7-11]. Those variables that remained significantly associated with obesity in multivariable analysis 1 were then included in a second multivariable model that also retained HIV status, age, gender and ethnicity (multivariable analysis 2). In order to test whether the association of risk factors for obesity in multivariable analysis 2 differed between PWH and HIV-negative controls, we added the interaction term for each of these factors (one at the time) with HIV-status in multivariable analysis 2. Associations of HIV-specific risk factors with obesity were assessed using logistic regression models restricted to PWH with adjustment for risk factors identified in multivariable analysis 2. HIV-related factors considered for these models were: prior AIDS; years since HIV diagnosis and ART start; current and nadir CD4 T-cell count; years with a CD4 T-cell count <200 cells/L; CD4 T-cell count recovery rate; current CD4:CD8 T-cell ratio; HIV RNA <50 copies/mL; and cumulative exposure to nucleoside reverse transcriptase inhibitors (NRTIs), tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), abacavir/lamivudine, non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs). In order to test the robustness of our results, two sensitivity analyses were performed for each model, one using BMI as a continuous variable and the other using presence of class II obesity (BMI ≥35 kg/m) as a binary outcome. Associations of obesity with quality-of-life (QoL, physical and mental health summary scales from the SF-36 questionnaire) and co-morbidities (CVD, type 2 diabetes, renal impairment, liver impair

The aims of the study were to describe the prevalence of obesity in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) cohort, to identify demographic, clinical and HIV-specific factors associated with obesity, and to characterize the association between obesity and sociodemographic, clinical and HIV-specific factors and quality of life (QoL). A cross-sectional analysis was carried out of baseline data from the three groups [“older” people with HIV infection (PWH) aged ≥ 50 years, “younger” PWH aged < 50 years and HIV-negative controls aged ≥ 50 years] within the POPPY cohort. Obesity was defined as a body mass index (BMI) > 30 kg/m 2 . A total of 1361 subjects were included in the study, of whom 335 (24.6%) were obese. The prevalence of obesity was higher in controls (22.3%) than in older (16.8%) and younger (14.2%) PWH, with no differences between the two groups of PWH. Factors associated with obesity were older age, female gender, black African ethnicity and alcohol consumption. Recreational drug use and a higher current CD4 T-cell count (in PWH) were associated with lower and higher odds of being obese, respectively. The presence of obesity was associated with worse physical health QoL scores, higher odds of having cardiovascular disease, type 2 diabetes and hypertension, but lower odds of having osteopenia/osteoporosis, irrespective of HIV status. Despite a lower prevalence of obesity in PWH, specific subgroups (women, people of black African origin and older people) were more likely to be obese, and negative health consequences of obesity were evident, regardless of HIV status. Whether targeted preventive strategies can reduce the burden of obesity and its complications in PWH remains to be determined.

The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients at 3 years follow up, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort which may help guide future trial design.