Objective: To explore the effects of microglial activation on brain function and structure, and its relationship with peripheral inflammatory markers, in treated, HIV-positive individuals, using in vivo [¹¹C]PBR28 PET (to measure the 18 kDa translocator protein [TSPO]). Methods: Cognitively healthy HIV-positive individuals on suppressive antiretroviral therapy and HIV-negative individuals (controls) underwent brain [¹¹C]PBR28 PET and MRI. HIV-positive patients completed neuropsychological testing and CSF testing for chemokines. The concentration of bacterial ribosomal 16sDNA in plasma was measured as a marker of microbial translocation. Results: HIV-positive individuals showed global increases in TSPO expression compared to controls (corrected p < 0.01), with significant regional increases in the parietal (p = 0.001) and occipital (p = 0.046) lobes and in the globus pallidus (p = 0.035). TSPO binding in the hippocampus, amygdala, and thalamus were associated with poorer global cognitive performance in tasks assessing verbal and visual memory (p < 0.05). Increased TSPO binding was associated with increased brain white matter diffusion MRI mean diffusivity in HIV-positive individuals, a lower CD4/CD8 ratio, and both high pretreatment HIV RNA and plasma concentration ribosomal 16s DNA (p < 0.05). Conclusions: Cognitively healthy HIV-positive individuals show evidence for a chronically activated brain innate immune response and elevated blood markers of microbial translocation despite effective control of plasma viremia. Increased brain inflammation is associated with poorer cognitive performance and white matter microstructural pathology, suggesting a possible role in cognitive impairments found in some HIV-positive patients despite effective treatment.

Cognitive disorders are a common issue impacting those living with human immunodeficiency virus (HIV). Effective antiretroviral treatment has lessened the severity but not the frequency of these impairments. Such deficits reduce quality of life and present a significant challenge to clinicians in the context of an ageing HIV population with a growing number of comorbidities. This review is based on recent published literature in the field of HIV-associated cognitive impairment (HAND). The pathogenesis of HAND is multifactorial and can be categorized into HIV viral factors, antiretroviral factors and individual factors. The risk factors associated with HAND are well documented. The prevalence of HAND in HIV populations varies and is dependent on populations studied and assessment batteries used. Disease progression is poorly understood and has important implication for screening programmes. The relative contribution of pathogenic mechanisms causing HAND is unclear, but recent papers point to inflammation as a significant contributor. The role of psychiatric diseases, such as depression, in the development and maintenance of HAND has recently been examined and requires clinical consideration. Furthermore, as the HIV population ages, its clinical management faces new challenges. Identifying biomarkers for HAND which are practical in a clinical setting and utilizing new imaging technologies to better monitor diagnosis and disease progression. Furthermore, the development of therapeutics targeting inflammation appears of increasing importance.

Syphilis, which is caused by the sexually transmitted bacterium Treponema pallidum subsp. pallidum , has an estimated 6.3 million cases worldwide per annum. In the past ten years, the incidence of syphilis has increased by more than 150% in some high-income countries, but the evolution and epidemiology of the epidemic are poorly understood. To characterize the global population structure of T. pallidum , we assembled a geographically and temporally diverse collection of 726 genomes from 626 clinical and 100 laboratory samples collected in 23 countries. We applied phylogenetic analyses and clustering, and found that the global syphilis population comprises just two deeply branching lineages, Nichols and SS14. Both lineages are currently circulating in 12 of the 23 countries sampled. We subdivided T. p. pallidum into 17 distinct sublineages to provide further phylodynamic resolution. Importantly, two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analyses revealed examples of isolates collected within the last 20 years from 14 different countries that had genetically identical core genomes, which might indicate frequent exchange through international transmission. It is striking that most samples collected before 1983 are phylogenetically distinct from more recently isolated sublineages. Using Bayesian temporal analysis, we detected a population bottleneck occurring during the late 1990s, followed by rapid population expansion in the 2000s that was driven by the dominant T. pallidum sublineages circulating today. This expansion may be linked to changing epidemiology, immune evasion or fitness under antimicrobial selection pressure, since many of the contemporary syphilis lineages we have characterized are resistant to macrolides.

Introduction Our aim was to describe episodic nature of disability among adults living with Long COVID. Methods We conducted a community-engaged qualitative descriptive study involving online semistructured interviews and participant visual illustrations. We recruited participants via collaborator community organisations in Canada, Ireland, UK and USA. We recruited adults who self-identified as living with Long COVID with diversity in age, gender, race/ethnicity, sexual orientation and duration since initial COVID infection between December 2021 and May 2022. We used a semistructured interview guide to explore experiences of disability living with Long COVID, specifically health-related challenges and how they were experienced over time. We asked participants to draw their health trajectory and conducted a group-based content analysis. Results Among the 40 participants, the median age was 39 years (IQR: 32–49); majority were women (63%), white (73%), heterosexual (75%) and living with Long COVID for ≥1 year (83%). Participants described their disability experiences as episodic in nature, characterised by fluctuations in presence and severity of health-related challenges (disability) that may occur both within a day and over the long-term living with Long COVID. They described living with ‘ups and downs’, ‘flare-ups’ and ‘peaks’ followed by ‘crashes’, ‘troughs’ and ‘valleys’, likened to a ‘yo-yo’, ‘rolling hills’ and ‘rollercoaster ride’ with ‘relapsing/remitting’, ‘waxing/waning’, ‘fluctuations’ in health. Drawn illustrations demonstrated variety of trajectories across health dimensions, some more episodic than others. Uncertainty intersected with the episodic nature of disability, characterised as unpredictability of episodes, their length, severity and triggers, and process of long-term trajectory, which had implications on broader health. Conclusion Among this sample of adults living with Long COVID, experiences of disability were described as episodic, characterised by fluctuating health challenges, which may be unpredictable in nature. Results can help to better understand experiences of disability among adults living with Long COVID to inform healthcare and rehabilitation.

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. 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. 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 %). 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.

Background: Polypharmacy (use of ≥ five medications) increases the risk of drug-drug interactions and can lead to negative health outcomes. This study aimed to review the medications of people living with HIV (PLWH) and HIV-negative controls in the POPPY study and evaluate the frequency of polypharmacy and potential drug-drug interactions (PDDIs). Methods: PDDIs between non-antiretroviral (ARV) drugs were analysed using the Lexicomp® database, and PDDIs between non-ARV and ARV drugs using the Liverpool drug interaction database. Between-group differences were assessed using χ ² , Mann-Whitney U and Kruskal-Wallis tests. Results: This analysis included 698 PLWH ≥50 years, 374 PLWH <50 years and 304 HIV-negative controls ≥50 years. The prevalence of polypharmacy was 65.8% in older PLWH, 48.1% in younger PLWH and 13.2% in the HIV-negative group. When ARVs were excluded, 29.8% of older PLWH and 14.2% of younger PLWH had polypharmacy. The prevalence of ≥1 PDDI involving non-ARV drugs was 36.1%, 20.3% and 16.4%, respectively, in older PLWH, younger PLWH and HIV-negative controls. In PLWH the prevalence of ≥1 PDDI involving ARV and non-ARV drugs was 57.3% in older PLWH and 32.4% in younger PLWH. Conclusions: Polypharmacy and PDDIs involving non-ARV/ARV drugs and non-ARV/non-ARV drugs were common among older PLWH, highlighting the need for increased awareness and additional research on all types of PDDI.