Is PPARγ a Prospective Player in HIV-1-Associated Bone Disease?

Currently infection with the human immunodeficiency virus-1 (HIV-1) is in most instances a chronic disease that can be controlled by effective antiretroviral therapy (ART). However, chronic use of ART has been associated with a number of toxicities; including significant reductions in bone mineral density (BMD) and disorders of the fat metabolism. The peroxisome proliferator-activated receptor gamma (PPARγ) transcription factor is vital for the development and maintenance of mature and developing adipocytes. Alterations in PPARγ expression have been implicated as a factor in the mechanism of HIV-1-associated lipodystrophy. Both reduced BMD and lipodystrophy have been well described as complications of HIV-1 infection and treatment, and a question remains as to their interdependence. Interestingly, both adipocytes and osteoblasts are derived from a common precursor cell type; the mesenchymal stem cell. The possibility that dysregulation of PPARγ (and the subsequent effect on both osteoblastogenesis and adipogenesis) is a contributory factor in the lipid- and bone-abnormalities observed in HIV-1 infection and treatment has also been investigated. This review deals with the hypothesis that dysregulation of PPARγ may underpin the bone abnormalities associated with HIV-1 infection, and treats the current knowledge and prospective developments, in our understanding of PPARγ involvement in HIV-1-associated bone disease

Antiretroviral Therapy and Dyslipidaemia: Unlocking the Code

Mallon discusses a new study that describes associations between apoC-III polymorphisms and triglyceride concentrations in a large population of HIV-infected patients from a variety of ethnic backgrounds

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

Circulating microparticles are increased amongst people presenting with HIV and advanced immune suppression in Malawi and correlate closely with arterial stiffness: a nested case control study [version 2; peer review: 2 approved, 1 approved with reservations]

BACKGROUND: We aim to investigate whether circulating microparticle (CMPs) subsets were raised amongst people presenting with a new diagnosis of HIV and advanced immune suppression in Malawi, and whether they associated with arterial stiffness. Methods: Microparticle characterisation and carotid femoral Pulse Wave Velocity (cfPWV) were carried out in a cohort of adults with a new HIV diagnosis and CD4 <100 cells/µL at 2 weeks post ART initiation. HIV uninfected controls were matched on age, systolic BP and diastolic BP in a 1:1 ratio. Circulating microparticles were identified from platelet poor plasma and stained for endothelial, leucocyte, monocyte and platelet markers. METHODS: Microparticle characterisation and carotid femoral Pulse Wave Velocity (cfPWV) were carried out in a cohort of adults with a new HIV diagnosis and CD4 <100 cells/µL at 2 weeks post ART initiation. HIV uninfected controls were matched on age, systolic BP and diastolic BP in a 1:1 ratio. Circulating microparticles were identified from platelet poor plasma and stained for endothelial, leucocyte, monocyte and platelet markers. RESULTS: The median (IQ) total CMP count for 71 participants was 1 log higher in HIV compared to those without (p<0.0001) and was associated with arterial stiffness (spearman rho 0.47, p<0.001). In adjusted analysis, every log increase in circulating particles showed a 20% increase in cfPWV (95% CI 4 – 40%, p=0.02). In terms of subsets, endothelial and platelet derived microparticles were most strongly associated with HIV. Endothelial derived E-selectin+ CMPs were 1.3log-fold higher and platelet derived CD42a+ CMPs were 1.4log-fold higher (both p<0.0001). Endothelial and platelet derived CMPs also correlated most closely with arterial stiffness [spearman rho: E-selectin+ 0.57 and CD42a 0.56, both p<0.0001). CONCLUSIONS: Circulating microparticles associate strongly with arterial stiffness among PLWH in Malawi. Endothelial and platelet microparticles are the predominant cell origin types, indicating that platelet driven endothelial dysfunction pathways warrant further investigation in HIV associated arterial stiffness

Pain in people living with HIV and its association with healthcare resource use, well-being and functional status

Objective: We describe the prevalence of pain and its associations with healthcare resource utilisation and quality-of-life. Design: The POPPY Study recruited three cohorts: older PLWH (≥50 years, n = 699), younger demographically/lifestyle similar PLWH (<50 years, n = 374) and older demographically/lifestyle similar HIV-negative (≥50 years, n = 304) people from April 2013-February 2016. Methods: Current pain and pain-related healthcare use was collected via a self-reported questionnaire. Logistic regression assessed between-group differences in the prevalence of pain in the past month and current pain after controlling for potential confounders. Associations between current pain and healthcare resource use, reported joint problems, depressive symptoms, quality-of-life and functional status were assessed in PLWH using Mann-Whitney U and Chi-squared tests. Results: Pain in the past month was reported by 473/676 (70.0%) older PLWH, 224/357 (62.7%) younger PLWH and 188/295 (63.7%) older HIV-negative controls (p = 0.03), with current pain reported in 330 (48.8%), 134 (37.5%) and 116 (39.3%), respectively (p = 0.0007). Older PLWH were more likely to experience current pain, even after adjustment for confounders. Of those with pain in the past month, 56/412 (13.6%) had missed days of work or study due to pain, and 520 (59%) had seen a doctor about their pain. PLWH experiencing current painhad more depressive symptoms, poorer quality-of-life on all domains, and greater functional impairment, regardless of age group. Conclusions: Even in the effective ART era, pain remains common in PLWH and has a major impact on quality-of-life and associated healthcare and societal costs. Interventions are required to assist clinicians and PLWH to proactively manage pain

Defining cognitive impairment in people-living-with-HIV: the POPPY study

Background The reported prevalence of cognitive impairment (CI) varies widely in cohorts of people living with HIV (PLWH); this may partly be due to the use of different diagnostic criteria. Agreement between diagnostic criteria of CI, the optimal definition to use, and associations with patient-reported cognitive symptoms have not been fully investigated. Methods Two hundred ninety PLWH aged >50 years and 97 matched negative controls completed a detailed assessment of cognitive function and three questions regarding cognitive symptoms. Age- and education-adjusted test scores (T-scores) determined if subjects met the following definitions of CI: Frascati, global deficit score (GDS) and the multivariate normative comparison (MNC) method. Results PLWH were more likely than controls to meet each definition of CI (ORs were 2.17, 3.12 and 3.64 for Frascati, GDS and MNC, respectively). Agreement of MNC with Frascati and GDS was moderate (Cohen’s k = 0.42 and 0.48, respectively), whereas that between Frascati and GDS was good (k = 0.74). A significant association was found between all the three criteria and reporting of memory loss but not with attention and reasoning problems. The 41 (14 %) PLWH meeting all the three criteria had the lowest median global T-score (36.9) and highest rate of symptom reporting (42 %). Conclusions Different CI criteria show fair diagnostic agreement, likely reflecting their ability to exclude CI in the same group of individuals. Given the lower overall cognitive performance and higher rates of symptom reporting in those meeting all three criteria of CI, further work assessing this as a definition of CI in PLWH is justified

Aging in HIV-Infected Subjects: A New Scenario and a New View

The prevalence of HIV-infected people aged 50 years or older is increasing rapidly; the proportion will increase from 28% to 73% in 2030. In addition, HIV-infected individuals may be more vulnerable to age-related condition. There is growing evidence that the prevalence of comorbidities and other age-related conditions (geriatric syndromes, functional or neurocognitive/mental problems, polypharmacy, and social difficulties) is higher in the HIV-infected population than in their uninfected counterparts. However, despite the potential impact of this situation on health care, little information exists about the optimal clinical management of older HIV-infected people. Here we examine the age-related conditions in older HIV-infected persons and address clinical management according to author expertise and published literature. Our aim is to advance the debate about the most appropriate management of this population, including less well-studied aspects, such as frequency of screening for psychological/mental and social and functional capabilities

Cohort profile: the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) study

No description supplie