Quality of Life, Health-Related Stigma, and the Social Context: Longitudinal Analyses of PLWHA in Uganda and a Literature Review

The dissertation examines the experience of living with stigmatized health conditions in the social context. The first paper examines the dynamic, bi-directional relationship between social support and HIV-related stigma. I use data from a prospective cohort of people living with HIV/AIDS (PLWHA) initiating antiretroviral therapy in rural Uganda. I use multilevel regression to model the contemporaneous and time-lagged relationships between two dimensions of stigma and social support. The results suggest that the two dimensions of stigma may compromise the ability to maintain and access social support. I also found that social support may be protective against future experiences of discrimination. The second paper examines the trajectory and determinants of health-related quality of life (HRQOL) of PLWHA initiating antiretroviral therapy. Using the same data set as paper one, I compared two types of multilevel models for change in which HRQOL is specified as linear and quadratic functions of time. Analyses indicated that HRQOL follows a quadratic trajectory that is concave to the time axis. Self-reported symptoms, food insecurity, and HIV-related stigma are negatively correlated with HRQOL, suggesting the importance of addressing social and economic situations of PLWHA in addition to clinical symptoms. The third paper is an interdisciplinary review of health-related stigma. The social psychology literature describes stigma as a product of individual traits and personalities that has roots in the biological instinct to avoid poor partners of social exchange. In contrast, the historical, anthropological, and autobiographical literatures highlight the role of social forces outside of the individual in the production of stigma. I argue that health-related stigma is based on the ever-changing understandings about disease causality that reflects contemporary ideas about morality. Further, stigmatization is contingent on a social structure in which differential access to social, economic and political power determines who is stigmatized. Finally, stigmatization dehumanizes individuals who are already vulnerable, and erects barriers to health and social resources to further exacerbate social inequalities. Therefore, health-related stigma should not be used as a tool to promote public health, and societal efforts should focus on eliminating health-related stigma

Life Chaos is Associated with Reduced HIV Testing, Engagement in Care, and ART Adherence Among Cisgender Men and Transgender Women upon Entry into Jail.

Life chaos, the perceived inability to plan for and anticipate the future, may be a barrier to the HIV care continuum for people living with HIV who experience incarceration. Between December 2012 and June 2015, we interviewed 356 adult cisgender men and transgender women living with HIV in Los Angeles County Jail. We assessed life chaos using the Confusion, Hubbub, and Order Scale (CHAOS) and conducted regression analyses to estimate the association between life chaos and care continuum. Forty-eight percent were diagnosed with HIV while incarcerated, 14% were engaged in care 12 months prior to incarceration, mean antiretroviral adherence was 65%, and 68% were virologically suppressed. Adjusting for sociodemographics, HIV-related stigma, and social support, higher life chaos was associated with greater likelihood of diagnosis while incarcerated, lower likelihood of engagement in care, and lower adherence. There was no statistically significant association between life chaos and virologic suppression. Identifying life chaos in criminal-justice involved populations and intervening on it may improve continuum outcomes

The Dynamic Relationship Between Social Support and HIV-Related Stigma in Rural Uganda

Background—Cross-sectional studies show that human immunodeficiency virus (HIV) stigma is negatively correlated with social support. Purpose—The purpose of this study is to examine the bidirectional relationship between social support and HIV stigma. Methods—We collected quarterly data from a cohort of 422 people living with HIV in Uganda, followed for a median of 2.1 years. We used multilevel regression to model the contemporaneous and 3-month-lagged associations between social support and both enacted and internalized stigma. Results—Lagged enacted stigma was negatively correlated with emotional and instrumental social support, and lagged instrumental social support was negatively correlated with enacted stigma. Internalized stigma and emotional social support had reciprocal lagged associations. Conclusions—Interventions to reduce enacted stigma may strengthen social support for people living with HIV. Improved social support may in turn have a protective influence against future enacted and internalized stigma

Social Network Correlates of Free and Purchased Insecticide-treated Bed Nets in Rural Uganda

Background Malaria is a major cause of mortality and morbidity in Uganda. Despite Uganda’s efforts to distribute bed nets, only half of households have achieved the World Health Organization (WHO) Universal Coverage Criteria (one bed net for every two household members). The role of peer influence on bed net ownership remains underexplored. Data on the complete social network of households were collected in a rural parish in southwestern Uganda to estimate the association between household bed net ownership and peer household bed net ownership. Methods Data on household sociodemographics, bed net ownership, and social networks were collected from all households across one parish in southwestern Uganda. Bed nets were categorized as either purchased or free. Purchased and free bed net ownership ratios were calculated based on the WHO Universal Coverage Criteria. Using network name generators and complete census of parish residents, the complete social network of households in the parish was generated. Linear regression models that account for network autocorrelation were fitted to estimate the association between households’ bed net ownership ratios and bed net ownership ratios of network peer households, adjusting for sociodemographics and network centrality. Results One thousand seven hundred forty-seven respondents were interviewed, accounting for 716 households. The median number of peer households to which a household was directly connected was 7. Eighty-six percent of households owned at least one bed net, and 41% of households met the WHO Universal Coverage Criterion. The median bed net ownership ratios were 0.67 for all bed nets, 0.33 for free bed nets, and 0.20 for purchased bed nets. In adjusted multivariable models, purchased bed net ownership ratio was associated with average household wealth among peer households (b = 0.06, 95% CI 0.03, 0.10), but not associated with average purchased bed net ownership ratio of peer households. Free bed net ownership ratio was associated with the number of children under 5 (b = 0.08, 95% CI 0.05, 0.10) and average free bed net ownership ratios of peer households (b = 0.66, 95% CI 0.46, 0.85). Conclusions Household bed net ownership was associated with bed net ownership of peer households for free bed nets, but not for purchased bed nets. The findings suggest that public health interventions may consider leveraging social networks as tools for dissemination, particularly for bed nets that are provided free of charge

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target