Biomarker associations with insomnia and secondary sleep outcomes in persons with and without HIV in the POPPY-Sleep substudy: a cohort study

Abstract

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

“…The distribution of demographic characteristics, CVD risk factors, and HIV-related factors are presented as counts (percentages) for categorical variables and medians (interquartile ranges [IQRs]) for quantitative variables. The analysis presented are based on inflammatory profiles (generated using data from both people with HIV as well as HIV-negative controls) identified from a previous study [19]. These profiles were generated using thirty-one biomarkers, related to eight inflammatory pathways (Table 3, Supplemental Digital Content, http://links.…”

“…The distribution of demographic characteristics, CVD risk factors, and HIV-related factors are presented as counts (percentages) for categorical variables and medians (interquartile ranges [IQRs]) for quantitative variables. The analysis presented are based on inflammatory profiles (generated using data from both people with HIV as well as HIV-negative controls) identified from a previous study [19]. These profiles were generated using thirty-one biomarkers, related to eight inflammatory pathways (Table 3, Supplemental Digital Content, http://links.lww.com/QAD/C773), that were analysed at the Centre for Experimental Pathogen Host Research (CEPHR), University College Dublin (UCD) using two immunoassay platforms based on Enzyme Linked Immunosorbent Assay (ELISA); Meso Scale Discovery (MSD; Rockland, Maryland, USA) and Luminex − MAGPIX (Luminex; R&D Systems, Minneapolis, Minnesota, USA).…”

“…In previous work, we used data from the Pharmacokinetic and clinical Observations in People over Fifty (POPPY)-Sleep sub-study to generate clinically relevant individual subgroups based on 31 plasma protein biomarkers [19]. Building on this work, the aim of the current study was to evaluate the associations between the inflammatory profiles and 10-year CVD risk, predicted using the QRISK, FRS, and D:A:D equations, in people with HIV and demographically/lifestyle-similar people without HIV.…”

Biomarkers of sleep and insomnia—challenges and opportunities

“…Such an approach, while practical and straightforward, likely obscures important immunologic complexities. The paper by Bakewell et al [ 4 ] takes a more comprehensive approach by using data from the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY)-Sleep substudy, which is comprised of participants 50 years or older diagnosed with HIV, 50 years or older demographically similar matched control group without HIV, and a younger sample of participants with HIV. All participants completed questionnaires about their sleep health, including insomnia symptoms, and wore a wrist actigraph and fingertip oximetry device for 1 week.…”