Biomarker Associations with Insomnia and Secondary Sleep Outcomes in Persons with and without HIV in the POPPY-Sleep Sub-study: a cohort study

STUDY OBJECTIVES: We investigated associations between inflammatory profiles/clusters and sleep measures in people living with HIV and demographically-/lifestyle-similar HIV-negative controls in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY)-Sleep sub-study. METHODS: Primary outcome was insomnia (Insomnia Severity Index [ISI]≥15). Secondary sleep outcomes included 7-day actigraphy (e.g. mean/standard deviation of sleep duration/efficiency), overnight oximetry (e.g. oxygen desaturation index [ODI]) and patient-reported measures (Patient-Reported Outcomes Measurement Information System (PROMIS) sleep questionnaires). Participants were grouped using Principal Component Analysis of 31 biomarkers across several inflammatory pathways followed by cluster analysis. Between-cluster differences in baseline characteristics and sleep outcomes were assessed using Kruskal-Wallis/logistic regression/Chi-squared/Fisher's exact tests. RESULTS: Of the 465 participants included (74% people with HIV, median [interquartile range] age 54 [50-60] years), only 18% had insomnia and secondary sleep outcomes suggested generally good sleep (e.g. ODI 3.1/hr [1.5-6.4]). Three clusters with distinct inflammatory profiles were identified: 'gut/immune activation' (n=47), 'neurovascular' (n=209), and 'reference' (relatively lower inflammation; n=209). The 'neurovascular' cluster included higher proportions of people with HIV, obesity (BMI≥30 kg/m 2), and previous cardiovascular disease, mental health disorder, and arthritis of knee/hip relative to the other two clusters. No clinically relevant between-cluster differences were observed in proportions with insomnia (17%, 18%, 20%) before (p=0.76) or after (p=0.75) adjustment for potential confounders. Few associations were observed among actigraphy, oximetry and PROMIS measures. CONCLUSIONS: Although associations could exist with other sleep measures or biomarker types not assessed, our findings do not support a strong association between sleep and inflammation in people with HIV

Association between inflammatory biomarker profiles and cardiovascular risk in individuals with and without HIV

Background: People with HIV have an increased risk for cardiovascular morbidity and mortality. Inflammation and immune activation may contribute to this excess risk. Methods: We assessed thirty-one biomarkers in a subset of POPPY participants and identified three distinct inflammatory profiles: ‘gut/immune activation’, ‘neurovascular’, and ‘reference’ (relatively low levels of inflammation). Ten-year CVD risk predictions were calculated using the QRISK, Framingham Risk Score (FRS) and the Data Collection on Adverse effects of anti-HIV Drugs (D:A:D) algorithms. The distributions of CVD risk scores across the different inflammatory profiles, stratified by HIV status, were compared using median quantile regression. Results: Of the 312 participants included (70% living with HIV, median [interquartile range; IQR] age 55 [51–60] years; 82% male; 91% white), 146, 36, and 130 were in the ‘gut/immune activation’, ‘neurovascular’, and ‘reference’ cluster, respectively. The median [IQR] QRISK scores were 9.3% (4.5–14.5) and 10.2% (5.5–16.9) for people with and without HV, respectively, with similar scores obtained with the FRS and D:A:D. We observed statistically significant differences between the distributions of scores in the three clusters among people with HV. In particular, median QRISK (5.8% [1.0–10.7] and 3.1% [0.3–5.8]) scores were higher, respectively, for those in the ‘gut/immune activation’ and ‘neurovascular’ clusters compared to those in the reference cluster. Conclusions: People with HIV with increased gut/immune activation have a higher CVD risk compared to those with relatively low inflammation. Our findings highlight that clinically important inflammatory subgroups could be useful to differentiate risk and maximise prediction of CVD among people with HIV

Associations between plasma nucleoside reverse transcriptase inhibitors concentrations and cognitive function in people with HIV

Objectives To investigate the associations of plasma lamivudine (3TC), abacavir (ABC), emtricitabine (FTC) and tenofovir (TFV) concentrations with cognitive function in a cohort of treated people with HIV (PWH). Methods Pharmacokinetics (PK) and cognitive function (Cogstate, six domains) data were obtained from PWH recruited in the POPPY study on either 3TC/ABC or FTC/tenofovir disoproxil fumarate (TDF)-containing regimens. Association between PK parameters (AUC0-24: area under the concentration-time curve over 24 hours, Cmax: maximum concentration and Ctrough: trough concentration) and cognitive scores (standardized into z-scores) were evaluated using rank regression adjusting for potential confounders. Results Median (IQR) global cognitive z-scores in the 83 PWH on 3TC/ABC and 471 PWH on FTC/TDF were 0.14 (-0.27, 0.38) and 0.09 (-0.28, 0.42), respectively. Higher 3TC AUC0-24 and Ctrough were associated with better global z-scores [rho = 0.29 (p = 0.02) and 0.27 (p = 0.04), respectively], whereas higher 3TC Cmax was associated with poorer z-scores [rho = -0.31 (p0.05). None of the FTC and TFV PK parameters were associated with global or domain cognitive scores. Conclusions Whilst we found no evidence of either detrimental or beneficial effects of ABC, FTC and TFV plasma exposure on cognitive function of PWH, higher plasma 3TC exposures were generally associated with better cognitive performance although higher peak concentrations were associated with poorer performance

Switching from abacavir to tenofovir disoproxil fumarate is associated with rises in soluble glycoprotein VI, suggesting changes in platelet-collagen interactions.

OBJECTIVES: Altered platelet function has been proposed as an underlying mechanism to explain increased risk of myocardial infarction in people living with HIV associated with use of the nucleoside reverse transcriptase inhibitor abacavir (ABC). We aimed to examine changes in platelet biomarkers in people living with HIV switching from ABC. METHODS: In a prospective, 48-week substudy of virally suppressed HIV-1-positive subjects randomized to remain on ABC/lamivudine (ABC/3TC) or switch to tenofovir disoproxil fumarate/emtricitabine, we measured soluble glycoprotein VI (sGPVI), soluble P-selectin, soluble CD40 ligand and von Willebrand factor in plasma collected over time and assessed differences using mixed effect models. RESULTS: Of 312 randomized participants, 310 were included in the analysis. Mean (SD) age 46.4 (9.3) years, 262 (85%) men and 201 (65%) white. At baseline, there was no significant between-group difference in sGPVI [tenofovir disoproxil fumarate/emtricitabine 3.75 (0.25) versus ABC/3TC 3.61 (0.22) ng/ml, P = 0.69]. Greater increases in sGPVI from baseline to week 48 occurred in those switched from ABC/3TC (effect size +0.57 ng/ml; 95% confidence interval, 0.2-0.94; P = 0.003). There was no significant baseline difference or change overtime in soluble P-selectin, soluble CD40 ligand or von Willebrand factor between groups. CONCLUSION: The significant increases in sGPVI that occur with a switch from ABC/3TC are suggestive of changes in platelet function centred on platelet/collagen interactions and potentially represent an underlying mechanism to explain increased risk of myocardial infarction with ABC.</p

Platelet function and HIV: a case–control study

Ontem, quando coloquei a mensagem Os media dos produtores, pareceu-me faltar alguma coisa no título.Hoje, ao ler uma notícia da newsletter Meios e Publicidade sobre um concurso a promover por um dos operadores de telefones celulares, resolvi o enigma. Produtores sempre houve, tendo-se profissionalizado e dado origem a empresas - nomeadamente de rádio e televisão. Nos primeiros anos da rádio, surgiram muitos amadores, fenómeno repetido nos anos 1980, com as rádios piratas ou livres. Ora, isto ..

Anticholinergic medications associated with falls and frailty in people with HIV

Background: Anticholinergic medications (ACMs) are associated with poorer age-related outcomes, including falls and frailty. We investigate associations between ACM use and recurrent falls and frailty among older (aged ≥50 years) people with HIV in the POPPY study. / Methods: Anticholinergic potential of co-medications at study entry was coded using the anticholinergic burden score, anticholinergic risk score, and Scottish Intercollegiate Guidelines Network score; drugs scoring ≥1 on any scale were defined as ACM. Associations with recurrent falls (two or more falls in the previous 28 days) and frailty (modified Fried's) were assessed using logistic regression adjusting for (1) possible demographic/lifestyle confounders and (2) clinical factors and depressive symptoms (Patient Health Questionnaire-9). / Results: ACM use was reported by 193 (28%) of 699 participants, with 64 (9%) receiving two or more ACM; commonly prescribed ACMs were codeine (12%), citalopram (12%), loperamide (9%), and amitriptyline (7%). Falls were reported in 63/673 (9%), and 126/609 (21%) met the frailty criteria. Both recurrent falls and frailty were more common in ACM users than in non-users (recurrent falls: 17% in users vs. 6% in non-users, p < 0.001; frailty: 32% vs. 17%, respectively, p < 0.001). Use of two or more ACMs was associated with increased odds of falls after adjustment for demographic/lifestyle factors (odds ratio [OR] 4.53; 95% confidence interval [CI] 2.06–9.98) and for clinical factors (OR 3.58; 95% CI 1.37–9.38). Similar albeit weaker associations were seen with frailty (OR 2.26; 95% CI 1.09–4.70 and OR 2.12; 95% CI 0.89–5.0, respectively). / Conclusions: ACM are commonly prescribed for people living with HIV, and evidence exists for an association with recurrent falls and frailty. Clinicians should be alert to this and reduce ACM exposure where possible

Changes in multimorbidity burden over a 3–5 year period among people with HIV

Introduction: As people living with HIV age, the increasing burden of multimorbidity poses a significant health challenge. The aims of this study were to identify common patterns of multimorbidity and examine changes in their burden, as well as their associations with risk factors, over a 3–5 year period in people with HIV, enrolled in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) study.Methods: Common multimorbidity patterns were identified in POPPY participants with HIV using principal component analysis, based on Somers’ D statistic. Multimorbidity burden scores were calculated for each participant/pattern at study entry/follow-up and were standardised relative to the mean in the sample at baseline (scores >0 thus reflect a greater number of comorbidities relative to the mean). Two multivariable linear regression models were fitted to examine the associations between risk factors and burden z-scores at baseline and change in z-scores over a 3–5 year period.Results: Five patterns were identified among the 1073 POPPY participants with HIV {median age [interquartile range (IQR)], 52 (47–59) years; 85% male and 84% white}: Cardiovascular diseases (CVDs), Sexually transmitted diseases (STDs), Neurometabolic, Cancer and Mental-gastro-joint. The multivariable linear regression showed that older age, behavioural factors (i.e., body mass index (BMI), history of injection drug use, current recreational drug use and sex between men), and HIV-specific factors (i.e., duration since HIV diagnosis and a prior AIDS diagnosis) were associated with higher multimorbidity burden at baseline. However, only three of the factors (age, BMI and duration since HIV diagnosis) were significantly associated with an increase in burden across specific patterns over time.Discussion: Key modifiable and non-modifiable factors contributing to an increase in burden of multimorbidity were identified. Our findings may inform the development of more targeted interventions and guidelines to effectively prevent and manage the rising burden of multimorbidity in people with HIV.</p