Global Prevalence of Chronic Pain in Women with HIV: A Systematic Review and Meta-analysis.

Chronic pain is common among people with human immunodeficiency virus (HIV) and detrimental to quality of life and overall health. It is often underdiagnosed, undertreated, and frankly dismissed in women with HIV, despite growing evidence that it is highly prevalent in this population. Thus, we conducted a systematic review and meta-analysis to estimate the global prevalence of chronic pain in women with HIV. The full protocol can be found on PROSPERO (identifier CRD42022301145). Of the 2984 references identified in our search, 36 were included in the systematic review and 35 in the meta-analysis. The prevalence of chronic pain was 31.2% (95% confidence interval [CI], 24.6%-38.7%; I2 = 98% [95% CI, 97%-99%]; P < .0001). In this global assessment, we found a high prevalence of chronic pain among women with HIV, underscoring the importance of understanding the etiology of chronic pain, identifying effective treatments, and conducting regular assessments in clinical practice.

Dolutegravir-containing HIV therapy reversibly alters mitochondrial health and morphology in cultured human fibroblasts and peripheral blood mononuclear cells.

OBJECTIVES: Given the success of combination antiretroviral therapy (cART) in treating HIV viremia, drug toxicity remains an area of interest in HIV research. Despite newer integrase strand transfer inhibitors (InSTIs), such as dolutegravir (DTG) and raltegravir (RAL), having excellent clinical tolerance, there is emerging evidence of off-target effects and toxicities. Although limited in number, recent reports have highlighted the vulnerability of mitochondria to these toxicities. The aim of the present study is to quantify changes in cellular and mitochondrial health following exposure to current cART regimens at pharmacological concentrations. A secondary objective is to determine whether any cART-associated toxicities would be modulated by human telomerase reverse transcriptase (hTERT). METHODS: We longitudinally evaluated markers of cellular (cell count, apoptosis), and mitochondrial health [mitochondrial reactive oxygen species (mtROS), membrane potential (MMP) and mass (mtMass)] by flow cytometry in WI-38 human fibroblast with differing hTERT expression/localization and peripheral blood mononuclear cells. This was done after 9 days of exposure to, and 6 days following the removal of, seven current cART regimens, including three that contained DTG. Mitochondrial morphology was assessed by florescence microscopy and quantified using a recently developed deep learning-based pipeline. RESULTS: Exposure to DTG-containing regimens increased apoptosis, mtROS, mtMass, induced fragmented mitochondrial networks compared with non-DTG-containing regimens, including a RAL-based combination. These effects were unmodulated by telomerase expression. All effects were fully reversible following removal of drug pressure. CONCLUSION: Taken together, our observations indicate that DTG-containing regimens negatively impact cellular and mitochondrial health and may be more toxic to mitochondria, even among the generally well tolerated InSTI-based cART.

British Columbia CARMA-CHIWOS Collaboration (BCC3): protocol for a community-collaborative cohort study examining healthy ageing with and for women living with HIV.

INTRODUCTION: Women living with HIV (WLWH) experience accelerated ageing and an increased risk of age-associated diseases earlier in life, compared with women without HIV. This is likely due to a combination of viral factors, gender differences, hormonal imbalance and psychosocial and structural conditions. This interdisciplinary cohort study aims to understand how biological, clinical and sociostructural determinants of health interact to modulate healthy ageing in WLWH. METHODS AND ANALYSIS: The British Columbia Children and Women: AntiRetroviral therapy and Markers of Aging-Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CARMA-CHIWOS) Collaboration (BCC3) study will enrol WLWH (n=350) and sociodemographically matched HIV-negative women (n=350) living in British Columbia. A subset of BCC3 participants will be past participants of CARMA, n≥1000 women and children living with and without HIV, 2008-2018 and/or CHIWOS, n=1422 WLWH, 2013-2018. Over two study visits, we will collect biological specimens for virus serologies, hormones and biological markers as well as administer a survey capturing demographic and sociostructural-behavioural factors. Sociodemographics, comorbidities, number and type of chronic/latent viral infections and hormonal irregularities will be compared between the two groups. Their association with biological markers and psychostructural and sociostructural factors will be investigated through multivariable regression and structural equation modelling. Retrospective longitudinal analyses will be conducted on data from past CARMA/CHIWOS participants. As BCC3 aims to follow participants as they age, this protocol will focus on the first study visits. ETHICS AND DISSEMINATION: This study has been approved by the University of British Columbia Children's and Women's Research Ethics Board (H19-00896). Results will be shared in peer-reviewed journals, conferences and at community events as well as at www.hivhearme.ca and @HIV_HEAR_me. WLWH are involved in study design, survey creation, participant recruitment, data collection and knowledge translation. A Community Advisory Board will advise the research team throughout the study.

Automated PD-L1 Scoring for Non-Small Cell Lung Carcinoma Using Open-Source Software.

PD-L1 expression in non-small cell lung cancer (NSCLC) is predictive of response to immunotherapy, but scoring of PD-L1 immunohistochemistry shows considerable interobserver variability. Automated methods may allow more consistent and expedient PD-L1 scoring. We aimed to assess the technical concordance of PD-L1 scores produced using free open source QuPath software with the manual scores of three pathologists. A classifier for PD-L1 scoring was trained using 30 NSCLC image patches. A separate test set of 207 image patches from 69 NSCLC resection cases was used for comparison of automated and manual scores. Automated and average manual scores showed excellent correlation (concordance correlation coeffecient = 0.925), though automated scoring resulted in significantly more 1-49% scores than manual scoring (p = 0.012). At both 1% and 50% thresholds, automated scores showed a level of concordance with our 'gold standard' (the average of three pathologists' manual scores) similar to that of individual pathologists. Automated scoring showed high sensitivity (95%) but lower specificity (84%) at a 1% threshold, and excellent specificity (100%) but lower sensitivity (71%) at a 50% threshold. We conclude that our automated PD-L1 scoring system for NSCLC has an accuracy similar to that of individual pathologists. The detailed protocol we provide for free open source scoring software and our discussion of the limitations of this technology may facilitate more effective integration of automated scoring into clinical workflows.