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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 substudy. 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/m2), 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 = .76) or after (p = .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.

Introduction Sleep problems are commonly reported in people with HIV (PWH) and may be exacerbated by HIV-induced inflammation. We determined associations between systemic inflammation and objective/subjective sleep measures in PWH and demographically/lifestyle similar HIV-negative controls. Methods Objective sleep measures from 7-day actigraphy (e.g. mean/standard deviation (SD) of wake after sleep onset [WASO], sleep duration/efficiency), overnight oximetry (oxygen desaturation index [ODI]), and patient-reported measures (Insomnia Severity Index [ISI] and Patient-Reported Outcomes Measurement Information System [PROMIS] sleep questionnaires) were assessed in participants in the multicenter POPPY-Sleep Study in the UK and Ireland. Principal Component Analysis using 31 plasma inflammatory biomarkers followed by cluster analysis previously identified 3 distinct inflammatory clusters: 1 (low inflammation), 2 (immune activation) and 3 (systemic inflammation). Baseline characteristics and between-cluster differences in sleep outcomes were assessed using Kruskal-Wallis or logistic regression/Chi-squared tests. Results The 465 participants (74% PWH, median [interquartile range] age 54 [50-60] years) were mainly male (80%), men having sex with men (71%) and white (88%). Among PWH, most (98%) were on antiretroviral therapy, 92% had viral load ≤50 cps/mL and CD4 cell count was 610 [470-785] cells/mm3. Overall, 18% met ISI criteria for insomnia (ISI≥ 15), and other sleep measures suggested generally good sleep (e.g., ODI 3.1/hr [1.5-6.4]). Clusters 1 (n=209), 2 (n=47) and 3 (n=209) differed significantly for HIV status (73%, 60%, 78%, p=0.03); BMI (24.8, 25.9, 26.2 kg/m2, p=0.002); systolic blood pressure (126, 135, 126 mmHg, p=0.002); cardiovascular disease (39%, 28%, 53%, p=0.001) and arthritis (8%, 9%,16%, p=0.02) – all factors associated with sleep problems. There were no clinically relevant between-biomarker-cluster differences in the proportions with insomnia (17%, 18%, 20%) either before (p=0.76) or after (p=0.75) adjustment for potential confounders. Few associations were observed among other actigraphy, oximetry and PROMIS measures. Conclusion Despite observed differences in clinical factors associated with sleep problems, we found no consistent or strong associations between inflammatory biomarker clusters and a range of sleep outcomes. Although associations could exist with other sleep outcomes (e.g. sleep architecture) or biomarker types (e.g. cerebrospinal fluid) not assessed, our findings do not support a strong association between sleep and plasma inflammatory biomarkers in this population. Support (If Any) NIH R01HL131049

OBJECTIVES The aim of this study was to evaluate the agreement between self-reported sleep measures and insomnia with objectively measured sleep parameters in people with HIV (PWH) and HIV-negative individuals. DESIGN A cross-sectional analysis of PWH and lifestyle-similar HIV-negative individuals. METHODS Self-reported measures included time spent in bed, sleep onset latency and a validated insomnia questionnaire. Objective measures were assessed via 7-days/nights of actigraphy data to determine average and intra-individual variability of several sleep measures (including time spent in bed and onset latency). Spearman's correlation coefficient and Cohen's κ were used to assess the agreement between self-reported and actigraphy-assessed measures. Associations between insomnia and actigraphy-assessed sleep parameters were evaluated using partial least-square discriminant analysis (PLS-DA). RESULTS We found fair correlation between self-reported and actigraphy-assessed time spent in bed in 342 PWH (rs = 0.46) and 119 HIV-negative individuals (rs = 0.48). Among PWH, the correlation did not differ by age, education, depressive symptoms and self-reported insomnia (all P > 0.05), but was stronger in men (P = 0.05) and in those with a BMI of at least 25 kg/m2 (P

Study Objectives We investigated associations between actigraphy-assessed sleep measures and cognitive function in people with and without HIV using different analytical approaches to better understand these associations and highlight differences in results obtained by these approaches. Methods Cognitive and 7-day/night actigraphy data were collected from people with HIV (PWH) and lifestyle-similar HIV-negative individuals from HIV and sexual health clinics in the United Kingdom/Ireland. A global cognitive T-score was obtained averaging the standardized individual cognitive test scores accounting for sociodemographics. Average and SD of 11 sleep measures over 7 days/nights were obtained. Rank regression, partial least-squares (PLS) regression, random forest, sleep dimension construct, and latent class analysis (LCA) were applied to evaluate associations between global T-scores and sleep measures. Results In 344 PWH (median age 57 years, 86% males), average sleep duration, efficiency, and wake after sleep onset were not associated with global T-scores according to rank regression (p = 0.51, p = 0.09, p = 0.16, respectively). In contrast, global T-scores were associated with average and SD of length of nocturnal awakenings, SD of maintenance efficiency, and average out-of-bed time when analyzed by PLS regression and random forest. No associations were found when using sleep dimensions or LCA. Overall, findings observed in PWH were similar to those seen in HIV-negative individuals (median age 61 years, 67% males). Conclusions Using multivariable analytical approaches, measures of sleep continuity, timing, and regularity were associated with cognitive performance in PWH, supporting the utility of newer methods of incorporating multiple standard and novel measures of sleep-wake patterns in the assessment of health and functioning.

Background Self-reported sleep quality is poor in persons with human immunodeficiency virus (PWH), but prior studies commonly used nonspecific questionnaires, investigated only single sleep disorders, or lacked human immunodeficiency virus (HIV)-negative controls. We addressed these limitations in the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Sleep Substudy by assessing PWH and HIV-negative controls for insomnia, restless legs syndrome (RLS), and sleep apnea (SA). Methods Previously enrolled POPPY participants coenrolled in this substudy without regard to sleep symptoms. Participants completed validated sleep assessments including the Insomnia Severity Index questionnaire, International Restless Legs Syndrome Study Group questionnaire, and in-home, wrist-worn overnight oximetry. They also completed health-related quality of life questionnaires including 36-item Short Form (SF-36) and Patient-Reported Outcomes Measurement Information System (PROMIS) sleep questionnaires. Results We enrolled 357 PWH (246 >50 years of age; 111 between 18 and 50 years) and 126 HIV-negative controls >50 years of age. Among PWH, criteria were met by 21% for insomnia, 13% for RLS, and 6% for SA. Compared with HIV-negative controls, PWH had a higher risk of insomnia (adjusted odds ratio, 5.3; 95% confidence interval, 2.2–12.9) but not RLS or SA. Compared with PWH without insomnia, those with insomnia reported significantly worse scores on all SF-36 and PROMIS components; fewer than 30% reported previous diagnosis or treatment for insomnia. Conclusions Insomnia was more common in PWH, associated with worse health-related quality of life, and frequently undiagnosed. Further research should focus on the pathogenesis of insomnia in PWH and the development of effective screening and intervention strategies for this unique population.

Background We investigate the association of widespread pain with sleep quality among people with HIV and HIV-negative controls. Setting UK-based cohort. Methods Pain information was collected through a pain mannikin identifying affected body sites; pain was classified as widespread if pain was reported in ≥4 of 5 body regions and in ≥7 of 15 body sites, and as regional otherwise. Sleep was assessed a median of 3.2 years later through 7-night actigraphy and through self-reported assessments of sleep quality. Chi-squared tests, Kruskal-Wallis tests, and linear/logistic regression considered associations between pain extent and sleep quality. Results Of the 414 participants, 74 (17.9%) reported widespread and 189 (45.7%) regional pain. Although there were few clear associations between actigraphy outcomes and pain extent, those with widespread and regional pain consistently reported poorer sleep quality on all self-reported measures than those with no pain. Median (interquartile range) insomnia severity index and Patient-reported Outcomes Measurement Information System (PROMIS) for sleep disturbance and sleep-related impairment scores were 12 (7-16), 55.3 (48.0-58.9), and 57.2 (48.9-61.3), respectively, for those with widespread pain, 8 (4-13), 51.2 (45.5-58.3), and 50.3 (43.6-56.1) for those with regional pain, and 5 (2-9), 47.9 (42.9-54.3), and 45.5 (41.4-50.3) for those with no pain (all P values 0.0001). Associations remained strong after adjustment for HIV status and other confounders, and were reduced but remained significant, after adjustment for depressive symptoms. Conclusions Widespread pain was not associated with objective measures of sleep but was strongly associated with self-reported assessments of sleep quality in people with HIV.

Long-acting injectable antiretroviral (LA-ARV) drugs with low toxicity profiles and propensity for drug-drug interactions are a goal for future ARV regimens. C34-PEG4-Chol is a novel cholesterol tagged LA HIV-fusion-inhibitor (FI). We assessed pre-clinical toxicology and first-in-human administration of C34-PEG4-Chol. Pre-clinical toxicology was conducted in 2 species. HIV-positive men were randomised to a single subcutaneous dose of C34-PEG4-Chol at incrementing doses or placebo. Detailed clinical (including injection site reaction (ISR) grading), plasma pharmacokinetic (time-to-minimum-effective-concentration (MEC, 25 ng/mL) and pharmacodynamic (plasma HIV RNA) parameters were assessed. In both mice and dogs, no-observed-adverse effect level (NOAEL) was observed at a 12 mg/kg/dose after two weeks. Of 5 men enrolled, 3 received active drug (10 mg, 10 mg and 20 mg). In 2 individuals grade 3 ISR occurred and the study was halted. Both ISR emerged within 12 hours of active drug dosing. No systemic toxicities were observed. The time-to-MEC was >72 and >96 hours after 10 and 20 mg dose, respectively, and mean change in HIV RNA was −0.9 log10 copies/mL. These human pharmacodynamic and pharmacokinetic data, although limited to 3 subjects, of C34-PEG-4-Chol suggest continuing evaluation of this agent as a LA-ARV. However, alternative administration routes must be explored.

Canada is a diverse society with several historic divides, which makes democratic governance challenging. There are reasons to suppose that governing in Canada may be becoming even more complex, and this could have important implications for political support. It is also conceivable that the Canadian case may reflect some of the same challenges that could affect many other post-industrial democracies. Several structural and lifestyle changes have been altering the socio-cultural mix of Canadian society, possibly contributing to the expansion of various new value divides. Because values play a prominent role in shaping people's policy demands and political preferences, it is plausible that such a transformation could elevate the degree of intra-societal stress on Canada's political system and make governing more complex. In this essay, we have two main objectives. The first is to employ data from the Canadian World Values Surveys to explore the possibility that value diversity across various new value divi...