Enhancing the delivery of comprehensive care for people living with HIV in Canada: insights from citizen panels and a national stakeholder dialogue.

BACKGROUND: People living with human immunodeficiency virus (HIV) are living longer with health-related disability associated with ageing, including complex conditions. However, health systems in Canada have not adapted to meet these comprehensive care needs. METHODS: We convened three citizen panels and a national stakeholder dialogue. The panels were informed by a plain-language citizen brief that outlined data and evidence about the challenge/problem, elements of an approach for addressing it and implementation considerations. The national dialogue was informed by a more detailed version of the same brief that included a thematic analysis of the findings from the panels. RESULTS: The 31 citizen panel participants emphasized the need for more prevention, testing and social supports, increased public education to address stigma and access to more timely data to inform system changes. The 21 system leaders emphasized the need to enhance person-centred care and for implementing learning and improvement across provinces, territories and Indigenous communities. Citizens and system leaders highlighted that policy actions need to acknowledge that HIV remains unique among conditions faced by Canadians. CONCLUSIONS: Action will require a national learning collaborative to support spread and scale of successful prevention, care and support initiatives. Such a collaborative should be grounded in a rapid-learning and improvement approach that is anchored on the needs, perspectives and aspirations of people living with HIV; driven by timely data and evidence; supported by appropriate decision supports and aligned governance, financial and delivery arrangements; and enabled with a culture of and competencies for rapid learning and improvement.

Influence of previous experience with and beliefs regarding anal cancer screening on willingness to be screened among men living with HIV.

BACKGROUND: Implementation of anal cancer screening requires the procedure to be acceptable to the target population. Our objective was to assess the beliefs of men living with HIV regarding anal cancer screening and identify factors associated with their willingness to participate in screening. METHODS: We developed a cross-sectional questionnaire using the Theory of Planned Behavior to examine beliefs regarding prevention of human papillomavirus (HPV)-related diseases, administered to men living with HIV in 2016-2017 in a multi-site HIV clinical cohort. Correspondence analysis was used to examine the interrelationships between men's beliefs and willingness to undergo anal cancer screening. We used multivariable proportional odds models to identify factors associated with increasing willingness. Results were reported as adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: Among 1677 male participants, the vast majority (90%) would be willing to undergo screening by "anal Pap test"; willingness clustered with positive beliefs (e.g. confident they can get screened; disagree that they will feel pain) in the correspondence analysis. Higher self-perceived risk for anal cancer and positive beliefs regarding screening were associated with higher willingness to be screened. Gay, bisexual and other men who have sex with men had higher willingness (aOR = 1.62; 95% CI: 1.15, 2.29) than heterosexual men. Racialized men reported lower willingness (aOR = 0.68; 95% CI: 0.54, 0.89) than white men. CONCLUSIONS: Men generally had positive beliefs and were willing to undergo screening, though there were differences by sexual orientation and racial identity. Tailored community-led initiatives could focus on men's understanding of their risk and expectations of anal cancer screening to facilitate participation.

Low human papillomavirus (HPV) vaccine uptake among men living with human immunodeficiency virus (HIV): Cross-sectional findings from a clinical cohort.

Men living with human immunodeficiency virus (HIV) are internationally recognized as a priority population for human papillomavirus (HPV) vaccination. Our objective was to explore HPV vaccine uptake among men living with HIV in Ontario, Canada, and investigate differences between vaccinated and unvaccinated men. We used data from a cross-sectional questionnaire administered between 2016 and 2017 among men living with HIV and participating in the Ontario HIV Treatment Network Cohort Study. We calculated the proportion vaccinated against HPV, described vaccination experiences, and HPV vaccine knowledge, and calculated differences in characteristics between vaccinated and unvaccinated men. Among 1651 men (mean age = 51 years, 72% identified as gay), 7% were vaccinated (95% confidence interval[CI] 5.5-7.9%); 85% received their first dose at a primary care or HIV clinic. Among unvaccinated men, 40% were unaware of the HPV vaccine, 65% reported low perceived risk for HPV, and 8% discussed HPV vaccination with a physician. Compared to unvaccinated men, vaccinated men were younger, most identified as gay, had a higher education/income, reported a higher number of recent sex partners, and had a history of bacterial sexually transmitted infections (STIs), HPV, anogenital warts, and/or anal cancer. Our findings reveal that few men living with HIV were vaccinated against HPV. This may be influenced by low HPV awareness, prohibitive cost, and lack of physician recommendation. Several men reporting lower socio-economic status, older men, and heterosexual, bisexual, and other men who have sex with men were missed for vaccination. Primary care and HIV clinics may be ideal locations to increase uptake.

Using concept mapping to explore the challenges associated with affording and accessing medications among people living with HIV in Ontario, Canada.

Antiretroviral medications are expensive, and people living with HIV often experience challenges accessing and paying for medication due to various obstacles. We used concept mapping to explore the challenges people living with HIV in Ontario, Canada, face when accessing medication. In brainstorming, 68 participants generated 447 statements in response to the focus prompt "Some people living with HIV have trouble getting and paying for prescription drugs because … ". These were consolidated into 77 statements, which were sorted (n = 30) and rated (n = 32) on importance and commonality. A ten-cluster concept map consisting of individual- and health system-related clusters was generated. Clusters included: (1) Stigma, (2) Medication-Related Issues, (3) Individual Challenges, (4) Basic Needs, (5) Immigration, (6) Coverage, (7) Trillium Drug Program, (8) Access to Services, (9) System-Level Issues and (10) Access to Professional Services. Statements in Coverage and Basic Needs were rated most important and common although there was variability by Ontario residence and drug coverage mechanisms. Strategies to address challenges were generated in Interpretation (n = 25 participants). Given that continuous access to antiretroviral therapy is necessary to fully realize treatment benefits, policies and interventions that address these challenges are needed.

Low human papillomavirus (HPV) knowledge related to low risk perception among men living with HIV: Implications for HPV-associated disease prevention.

Human papillomavirus (HPV)-associated anal cancer is orders of magnitude higher among men living with HIV than the general male population. Our objective was to examine factors associated with HPV awareness and self-perceived risk for HPV-associated anal cancer among men living with HIV, which may influence uptake of cancer prevention strategies. A cross-sectional questionnaire on HPV was administered from 2016 to 2017 to 1677 men in a multisite, HIV clinical cohort in Ontario, Canada. We used logistic regression and proportional odds models to identify factors associated with being familiar with HPV and increasing self-perceived risk for anal cancer, respectively. We used correspondence analysis to examine associations of specific HPV-related knowledge with self-perceived risk. Only 52% were familiar with HPV, and 72% felt they had no or low risk for anal cancer. Familiarity with HPV was more common among men who have sex with men than heterosexual men (58% vs. 21%). Older men were less likely to be familiar with HPV (adjusted odds ratio [aOR] per 10 years = 0.77; 95% confidence interval [CI]: 0.69, 0.85). Familiarity with HPV was associated with increasing self-perceived risk (aOR = 2.39; 95% CI: 1.87, 3.04). After accounting for differences in HPV awareness and sexual orientation, racialized men had lower self-perceived risk (aOR = 0.68; 95% CI: 0.52, 0.88). In the correspondence analysis, risk-focused HPV-related knowledge (e.g., knowing smoking increases risk) was associated with highest risk perception. Efforts are needed to improve HPV-related health literacy in this population. Our findings suggest specific HPV-related knowledge may differentially influence self-perceived risk for anal cancer.

Economic barriers, evidentiary gaps, and ethical conundrums: a qualitative study of physicians' challenges recommending HPV vaccination to older gay, bisexual, and other men who have sex with men.

BACKGROUND: The human papillomavirus (HPV) is the most common sexually transmitted infection (STI) worldwide. Gay, bisexual, and other men who have sex with men (GBM), and GBM living with HIV in particular, are disproportionately impacted by HPV-associated cancers. The HPV vaccine, given early enough in life, may markedly reduce the likelihood of such cancers. In Canada, most provincial insurance programs only cover HPV vaccination for GBM up to the age of 26. Our objective was to understand physicians' everyday experiences and challenges in recommending HPV vaccination to older GBM patients. METHODS: As part of the HPV Screening and Vaccine Evaluation (HPV-SAVE) Study, we conducted semi-structured interviews with 25 HIV-positive GBM patients who had received anal cancer screening and 15 service providers, including 13 physicians, who had arranged for anal cancer screening in the Canadian provinces of Ontario and British Columbia. In this analysis, we draw upon the 13 physician interviews, which were coded following Grounded Theory. RESULTS: Physicians strongly supported the HPV vaccine for all GBM and considered it to be important for the management of HIV-related care. However, the overall support for HPV vaccination among physicians did not translate into consistent recommendation practices. There were two overarching factors that limited the strength/frequency of physicians' vaccine recommendation practices. First, cost/insurance coverage for some older patients impacted if and how the HPV vaccine was discussed. Second, physicians had diverse perspectives on both the prevention and therapeutic benefits of vaccinating older GBM and the reality that national guidelines are incongruent with publicly funded vaccine programs for vaccinating patients over 26 years old. These two interrelated factors have co-produced an apparent economic-evidentiary conundrum for many physicians regarding how and for whom to offer HPV vaccination. CONCLUSION: Economic barriers coupled with evidentiary and guideline gaps have created clinical practice challenges for physicians and has resulted in different messages being communicated to some older GBM patients about how important HPV vaccination is for their health.

Assessing Timely Presentation to Care Among People Diagnosed with HIV During Hospital Admission: A Population-Based Study in Ontario, Canada.

Timely presentation to care for people newly diagnosed with HIV is critical to optimize health outcomes and reduce onward HIV transmission. Studies describing presentation to care following diagnosis during a hospital admission are lacking. We sought to assess the timeliness of presentation to care and to identify factors associated with delayed presentation. We conducted a population-level study using health administrative databases. Participants were all individuals older than 16 and newly diagnosed with HIV during hospital admission in Ontario, Canada, between April 1, 2007 and March 31, 2015. We used modified Poisson regression models to derive relative risk ratios for the association between sociodemographic and clinical variables and the presentation to out-patient HIV care by 90 days following hospital discharge. Among 372 patients who received a primary HIV diagnosis in hospital, 83.6% presented to care by 90 days. Following multivariable analysis, we did not find associations between patient sociodemographic or clinical characteristics and presentation to care by 90 days. In a secondary analysis of 483 patients diagnosed during hospitalization but for whom HIV was not recorded as the principal reason for admission, 73.1% presented to care by 90 days. Following multivariable adjustment, we found immigrants from countries with generalized HIV epidemics (RR 1.265, 95% CI 1.133-1.413) were more likely to present to care, whereas timely presentation was less likely for people with a mental health diagnosis (RR 0.817, 95% CI 0.742-0.898) and women (RR 0.748, 95% CI 0.559-1.001). Future work should evaluate mechanisms to facilitate presentation to care among these populations.

Patient activation among people living with HIV: a cross-sectional comparative analysis with people living with diabetes mellitus.

Standardized self-management supports are an integral part of care delivery for many chronic conditions. We used the validated Patient Activation Measure (PAM®) to assess level of engagement for self-management from a sample of 165 people living with HIV (PLWH) and 163 people with diabetes. We conducted multivariable logistic regression to assess associations between demographics and PAM® scores. PLWH had high levels of activation that were no different from those of people with diabetes (mean score = 67.2, SD = 14.2 versus 65.0, SD = 14.9, p = 0.183). After adjusting for patient characteristics, only being on disability compared to being employed or a student was associated with being less activated (AOR = 0.276, 95%CI = 0.103-0.742). Our findings highlight the potential for the implementation of existing standardized chronic disease self-management programs to enhance the care delivery for PLWH, with people on disability as potential target populations.

Challenges with access to healthcare from the perspective of patients living with HIV: a scoping review & framework synthesis.

Accessing healthcare can be difficult but the barriers multiply for people living with HIV (PLHIV). To improve access and the health of PLHIV, we must consider their perspectives and use them to inform standard practice. A better understanding of the current literature related to healthcare access from the perspective of PLHIV, can help to identify evidence gaps and highlight research priorities and opportunities. To identify relevant peer-reviewed publications, search strategies were employed. Electronic and grey literature databases were explored. Articles were screened based on their title and abstract and those that met the screening criteria, were reviewed in full. Data analysis was conducted using a collaborative approach that included knowledge user consultation. Initial concepts were extracted, summarized and through framework synthesis, developed into emerging and final themes. From 20,678 articles, 326 articles met the initial screening criteria and 64 were reviewed in full. The final themes identified, in order of most to least frequent were: Acceptability, Availability, Accessibility, Affordability, Other Barriers, Communication, Satisfaction, Accommodation, Preferences and Equity in Access. The most frequently discussed concepts related to negative interactions with staff, followed by long wait times, limited household resources or inability to pay fees, and fear of one's serostatus being disclosed. Knowledge users were in agreement with the categorization of initial concepts and final themes; however, some gaps in the literature were identified. Specific changes are critical to improving access to healthcare for PLHIV. These include improving availability by ensuring staff and healthcare professionals have proper training, cultivating acceptability and reducing stigma through improving HIV awareness, increasing accessibility through increased HIV information for PLHIV and improved dissemination of this information to increase patient knowledge and health awareness. Finally, ensuring proper protocols are implemented and followed to guarantee patient confidentiality and overall satisfaction with healthcare services are recommended.

Donating One's Body to HIV Cure Research Through Canadian Medical Assistance in Dying: A Case Study.

BACKGROUND: Finding a cure for HIV is challenged by persisting reservoirs, the mapping of which necessitates invasive procedures. Inviting people with HIV (PWHIV) at the end of life to donate body specimens post-mortem through research autopsies is a novel approach, raising ethical concerns. OBJECTIVE: This case study aims to explore the motivations, barriers, and facilitators of a terminally-ill Canadian PWHIV who requested medical assistance in dying (MAID) and expressed interest in donating his body for HIV cure research. CASE PRESENTATION: An in-depth 3-hour and semi-structured interview was conducted with the participant. The interview transcription was thematically coded to identify motivations and perceived barriers and facilitators to participate in end-of-life HIV cure research. Our analysis identified six themes. Two themes expressed motivations: Collaboration in progress in health and science, seeing cure research as collaboration with professionals; and Opportunity to learn more, mostly about science and health. One theme expressed a barrier: Losing interest in or identification with long-term care research matters, especially those related to the management of long-term care. Three themes expressed by facilitators: Receiving information from professionals one trusts and knows, especially clinical and research teams; Perceiving research procedures as simple, useful, and embedded in care, perceiving clinical, educational, and interpersonal benefits that surpass costs of participation; and Perceiving research as one last way to contribute, that is, feeling useful or give back. CONCLUSION: Several circumstances facilitated the patient's participation: being a single man, having time to participate, having no strong religious belief, and valuing clear, direct communication. His motivations to participate in HIV cure research were altruistic, and also an experience of working with clinical and research teams. Finally, this perspective highlights HIV cure research participant candidates' need for education about research procedures.

Correlates of Healthy Aging in Geriatric HIV (CHANGE HIV)-CTN 314.

The Correlates of Healthy Aging in Geriatric HIV (CHANGE HIV) study, CTN 314, is the first Canadian cohort of people living with HIV aged 65 years and older. The cohort was established with the purpose of characterizing the multidimensional health status of this population and identifying factors influencing healthy aging. The study builds on the World Health Organization (WHO) Aging and Health conceptual framework, generating a comprehensive profile of health domains (physical, social, mental health, cognitive function, and quality of life), health determinants (biologic, personal, and environmental), and HIV-specific factors that may interact with and influence health in people aging with HIV. The data for the first 353 participants are presented, focusing on sociodemographic factors, comorbidities, coinfections, frailty, cognitive function, loneliness, and resilience using a sex/gender stratified analysis. The cohort thus far is 91% men and the median age is 70 years (range from 65 to 85). Several vulnerabilities were observed, including a high prevalence of comorbidities and frailty. Women especially faced financial insecurity and precarious social structures; a large proportion live alone and only 6% are married or in steady relationships. Identifying strategies to address these vulnerabilities will empower people aging with HIV to optimize their health, quality of life, and independence.

Randomized, Blinded, Placebo-Controlled Trial of De Simone Formulation Probiotic During HIV-Associated Suboptimal CD4+ T Cell Recovery.

OBJECTIVE: To assess whether probiotic supplementation may reduce disease-linked systemic immune activation in people living with HIV with the immunologic nonresponder phenotype. DESIGN: Phase 2b, randomized, double-blind, placebo-controlled pilot trial. METHODS: HIV-positive individuals with blood CD4+ T-cell counts <350/mm3 despite viral suppression were randomized to 2:1 to receive De Simone Formulation Probiotic (DSFP; "Visbiome" commercially) or placebo for 48 weeks; target enrollment was 36 patients. The primary endpoint was the change in blood CD8+ T-cell coexpression of human leukocyte antigen-DR isotype and CD38 ("CD8 activation"). Secondary endpoints included biomarkers of inflammation, immune reconstitution, bacterial translocation, and gut permeability. Adjusted linear regression and linear mixed regression methods evaluated the differences between study arms from baseline to week 48. Study monitoring was performed by the CIHR Canadian HIV Trials Network Data Safety Monitoring Committee. RESULTS: Nineteen patients received DSFP, whereas 10 received placebo. One probiotic arm patient withdrew early. Blood CD8 activation increased 0.82 percentage points (pp) in the probiotic arm (95% confidence interval: -1.23 to 2.87;) and decreased by 2.06 pp in the placebo arm (-4.81 to 0.70; between arms P = 0.097). CD4+ T-cell activation (%HLA-DR+) decreased in the placebo arm [-3.79 pp (-7.32 to -0.26)] but increased in the probiotic arm [1.64 (-0.98 to 4.26); between arms P = 0.018]. No differences were observed in plasma or urine biomarkers of inflammation or microbial translocation. CONCLUSIONS: Blood immune activation markers in immunologic nonresponder individuals on effective antiretroviral treatment were not reduced by supplementation with DSFP; CD4+ T-cell activation may have been increased.

Willingness of Older Canadians with HIV to Participate in HIV Cure Research Near and After the End of Life: A Mixed-Method Study.

HIV cure research requires interrogating latent HIV reservoirs in deep tissues, which necessitates autopsies to avoid risks to participants. An HIV autopsy biobank would facilitate this research, but such research raises ethical issues and requires participant engagement. This study explores the willingness to participate in HIV cure research at the end of life. Participants include Canadians with HIV [people with HIV (PWHIV)] aged 55 years or older. Following a mixed-method study design, all participants completed a phone or online survey, and a subset of participants participated in in-depth phone or videoconference interviews. We produced descriptive statistics of quantitative data and a thematic analysis of qualitative data. Barriers and facilitators were categorized under domains of the Theoretical Domains Framework. From April 2020 to August 2021, 37 participants completed the survey (mean age = 69.9 years old; mean duration of HIV infection = 28.5 years), including 15 interviewed participants. About three quarters of participants indicated being willing to participate in hypothetical medical studies toward the end of life (n = 30; 81.1%), in HIV biobanking (n = 30; 81.1%), and in a research autopsy (n = 28; 75.7%) to advance HIV cure research, mainly for altruistic benefits. The main perceived risks had to do with physical pain and confidentiality. Barriers and facilitators were distributed across five domains: social/professional role and identity, environmental context and resources, social influences, beliefs about consequences, and capabilities. Participants wanted more information about study objectives and procedures, possible accommodations with their last will, and rationale for studies or financial interests funding studies. Our results indicate that older PWHIV would be willing to participate in HIV cure research toward the end of life, HIV biobanking, and research autopsy. However, a dialogue should be initiated to inform participants thoroughly about HIV cure studies, address concerns, and accommodate their needs and preferences. Additional work is required, likely through increased community engagement, to address educational needs.

A randomized control trial of high-dose micronutrient-antioxidant supplementation in healthy persons with untreated HIV infection.

BACKGROUND: Although micronutrient and antioxidant supplementation are widely used by persons with human immunodeficiency virus (HIV), a therapeutic role beyond recommended daily allowances (RDA) remains unproven. An oral high-dose micronutrient and antioxidant supplement (Treatment) was compared to an RDA supplement (Control) for time to progressive immunodeficiency or initiation of antiretroviral therapy (ART) in people living with HIV (PLWH). METHODS: This study was a randomized, double-blind, placebo-controlled multicenter clinical trial. PLWH were recruited from Canadian HIV Trials Network sites, and followed quarterly for two years. Eligible participants were asymptomatic, antiretroviral treatment (ART)-naïve, HIV-seropositive adults with a CD4 T lymphocyte count (CD4 count) between 375-750 cells/µL. Participants were randomly allocated 1:1 to receive Treatment or Control supplements. The primary outcome was a composite of time-to-first of confirmed CD4 count below 350 cells/µL, initiation of ART, AIDS-defining illness or death. Primary analysis was by intention-to-treat. Secondary outcomes included CD4 count trajectory from baseline to ART initiation or two years. A Data and Safety Monitoring Board reviewed the study for safety, recruitment and protocol adherence every six months. RESULTS: Of 171 enrolled participants: 66 (38.6%) experienced a primary outcome: 27 reached a CD4 count below 350 cells/µL, and 57 started ART. There was no significant difference in time-to-first outcome between groups (Hazard Ratio = 1.05; 95%CI: 0.65, 1.70), or in time to any component outcome. Using intent-to-treat censoring, mean annualized rates of CD4 count decline were -42.703 cells/µL and -79.763 cells/µL for Treatment and Control groups, with no statistical difference in the mean change between groups (-37.06 cells/µL/52 weeks, 95%CI: (-93.59, 19.47); p = 0.1993). Accrual was stopped at 171 of the 212 intended participants after an interim analysis for futility, although participant follow-up was completed. CONCLUSIONS: In ART-naïve PLWH, high-dose antioxidant, micronutrient supplementation compared to RDA supplementation had no significant effect on disease progression or ART initiation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00798772.

Four-year follow-up of polyalkylimide gel use for the treatment of HIV-associated lipoatrophy.

PURPOSE: To evaluate polyalkylamide gel (PAIG) use in treating HIV-associated facial lipoatrophy (FLA) 4 years after its injection in an open-label, randomized controlled trial (RCT). METHODS: Five patients were treated with PAIG in a pilot study, and 31 patients were subsequently enrolled in the RCT of immediate or delayed (12 weeks later) PAIG injections. Endpoints included proportion of participants with complications; changes in FLA severity score (FLSS); and quality of life (QoL), depression, anxiety, and satisfaction scores. Infections were classified as "confirmed" if purulent material was extracted and/or an organism cultured. Infections were classified as "possible" if only clinical signs were present without purulent discharge or microbiologic confirmation. RESULTS: Year 4 results were available for 5 pilot and 27 full-scale study participants. Delayed complications included 5 confirmed infections (15.6%), 3 possible infections (9.4%), nodules (25%), and bleeding (3%). No significant changes were observed between years 2 to 4 in patient-graded FLSS, QoL, depression, and anxiety scores. Whereas 94% of participants were satisfied with their overall treatment, only 69% were satisfied with PAIG treatment specifically. CONCLUSION: Even though PAIG treatment was associated with delayed complications including high rates of infection and nodules, most patients were satisfied with the treatment.

Ethnicity and gender differences in lipodystrophy of HIV-positive individuals taking antiretroviral therapy in Ontario, Canada.

PURPOSE: This study assessed ethnicity and gender differences in prevalence, type, and severity of antiretroviral-associated lipodystrophy in HIV-positive individuals in Ontario. METHODS: This was a cross-sectional analysis of the Ontario Cohort Study (OCS), a prospective study of HIV-positive patients in Ontario. Lipodystrophy was defined as at least 1 major or 2 minor self-reported changes of peripheral lipoatrophy and/or central lipohypertrophy. Prevalence, type, and severity were compared by ethnicity (Black, White, or Other) and gender. Univariate and multivariate logistic regression analyses identified predictors of lipodystrophy. RESULTS: Data were available for 778 participants (659 men, 119 women). There were 517 Whites, 121 Blacks, and 140 patients of Other ethnicities. In univariate analyses, Whites reported more peripheral lipoatrophy (P = .004) and abdominal lipohypertrophy (P = .04); these ethnic differences were observed in males (P = .05 and P = .03, respectively) but not females. Males reported more peripheral lipoatrophy (P = .01), whereas females had more central lipohypertrophy (P < .0001) and mixed fat redistribution (P < .0001). Multivariable regression analyses revealed Black women to be most vulnerable to lipodystrophy (P = .02), particularly lipohypertrophy (P < .0001). CONCLUSIONS: Ethnicity and gender are important factors influencing lipodystrophy. Combining lipoatrophy and lipohypertrophy into a single entity is not appropriate. Black women were most vulnerable to lipohypertrophy, which has important implications for antiretroviral therapy roll-out in Africa.

The Dietary Inflammatory Index Is Not Associated With Gut Permeability or Biomarkers of Systemic Inflammation in HIV Immunologic Non-responders.

Immunologic non-responders (INRs) are a subset of individuals living with HIV who have suboptimal blood CD4+ T cell recovery despite effective antiretroviral therapy (ART). They are at an increased risk of serious non-AIDS co-morbidities and death, and demonstrate enhanced systemic immune activation. In other populations diet has been correlated with markers of systemic inflammation through the Diet Inflammatory Index (DII), but this association has not been studied in persons living with HIV (PLWH). Blood was collected from 28 INR PLWH with a blood CD4+ T cell count <350/µL despite ≥2 years of effective ART. Participants completed a Canadian Diet History Questionnaire, and their responses were used to calculate the DII. Plasma inflammatory markers (IFNγ, TNF, IL-6, sVCAM, D-dimer, sCD14 and CRP) were assayed by ELISA, cellular immune activation (HLA-DR and CD38 on CD4+ and CD8+ T cells) was quantified using flow cytometry, and small bowel permeability assessed by calculation of the urine LacMan ratio after drinking a mix of lactulose and mannitol. Participants were a median age of 57 years, had been on effective ART for 15 years, and the median DII was -1.91 (range of -3.78 to +2.23). No correlation was observed between DII and plasma markers of inflammation, levels of T cell activation, gut permeability, or the biomarker of bacterial translocation sCD14. Self-reported alcohol intake, a potential confounder of the relationship between diet and inflammatory biomarkers, was also not associated with systemic inflammation or gut permeability. Our findings suggest that other mechanisms, rather than diet, are likely to be the major driver of systemic inflammation in INR individuals.

Diagnosing uncertainty: The challenges of implementing medical screening programs for minority sub-populations in Canada.

The social science literature on medical screening has documented a notable disjuncture between the promises of population-based screening programs and the complex realities of their rollout in everyday practice. We contribute to this scholarship by examining how healthcare providers confront numerous uncertainties associated with the implementation of anal cancer screening programs in Canada given the absence of standardized national evidence-based guidelines. The data was derived from in-depth interviews conducted with 13 physicians and 2 clinical researchers about anal cancer screening for gay, bisexual and other men who have sex with men living with HIV, the minority sub-population at the highest risk for HPV-associated anal cancer. Despite having unknown utility and low specificity, an initial anal Pap test was used to triage patients into anal dysplasia clinics for high-resolution anoscopy. This process led to technological scepticism toward the Pap's accuracy, diagnostic ambiguity related to the interpretation of the cytology results and increased patient anxiety regarding abnormal results. Physicians navigated a tension between wanting to avoid exposing their patients to additional uncertainties caused by screening and pre-cancer treatment and wanting to ensure that their patients did not develop anal cancer under their care. A high number of abnormal anal Pap results paradoxically reintroduced some of the capacity issues that the Pap was meant to resolve, as the existing dysplasia clinics were incapable of seeing all patients with abnormal results. We define this sequence as the epistemic-capacity paradox, a dynamic whereby seeking evidence to improve healthcare capacity simultaneously produces evidence that introduces capacity challenges and generates additional uncertainty. The epistemic-capacity paradox demonstrates the limitations of evidence-based medicine frameworks at determining best practices in the context of rarer health conditions affecting minority sub-populations, where smaller population numbers and limited institutional support pose systemic challenges to the acquisition of sufficient evidence.

Racial Disparities in Anal Cancer Screening Among Men Living With HIV: Findings From a Clinical Cohort Study.

BACKGROUND: Our objective was to quantify the extent of anal cancer screening among men receiving HIV specialty care in Ontario, Canada, and evaluate factors associated with screening. SETTING: Cross-sectional questionnaire within a multisite clinical HIV cohort. METHODS: A questionnaire assessing knowledge and experience with human papillomavirus-associated diseases and their prevention was administered in 2016-2017 to 1677 men in the Ontario HIV Treatment Network Cohort Study. We used logistic regression to identify factors associated with having discussed screening with a health care provider and self-reported receipt of screening [digital anal rectal examinations (DARE); anal cytology or anoscopy]. Results reported as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: Forty percent of men reported ever having had anal cytology/anoscopy, and 70% had ever had DARE. After accounting for differences in age, sexual orientation, years since HIV diagnosis, previous diagnosis with AIDS, knowing someone with human papillomavirus-associated cancer, comfort discussing anal health, education, and income, the proportion screened differed by self-identified race. Compared with white men, Asian men were less likely to have discussed screening with a health care provider (aOR = 0.48; 95% CI: 0.29 to 0.80) or to have been screened by DARE (aOR = 0.27; 95% CI: 0.17 to 0.44) or anal cytology/anoscopy (aOR = 0.51; 95% CI: 0.31 to 0.83), and African, Caribbean, or black men (aOR = 0.47; 95% CI: 0.31 to 0.70) were less likely to have had DARE. Results were consistent when restricting the analyses to gay, bisexual, and other men who have sex with men. CONCLUSION: Our findings highlight the potential for disparities in anal cancer screening that need to be considered when developing guidelines and screening programs to reduce the burden of anal cancer among men living with HIV and ensure health equity.