Social and structural barriers and facilitators to HIV healthcare and harm reduction services for people experiencing syndemics in Manitoba: study protocol.

INTRODUCTION: In Manitoba, Canada, there has been an increase in the number of people newly diagnosed with HIV and those not returning for regular HIV care. The COVID-19 pandemic resulted in increased sex and gender disparities in disease risk and mortalities, decreased harm reduction services and reduced access to healthcare. These health crises intersect with increased drug use and drug poisoning deaths, houselessness and other structural and social factors most acutely among historically underserved groups. We aim to explore the social and structural barriers and facilitators to HIV care and harm reduction services experienced by people living with HIV (PLHIV) in Manitoba. METHODS AND ANALYSIS: Our study draws on participatory action research design. Guiding the methodological design are the lived experiences of PLHIV. In-depth semi-structured face-to-face interviews and quantitative questionnaires will be conducted with two groups: (1) persons aged ≥18 years living or newly diagnosed with HIV and (2) service providers who work with PLHIV. Data collection will include sex, gender, sociodemographic information, income and housing, experiences with the criminal justice system, sexual practices, substance use practices and harm reduction access, experiences with violence and support, HIV care journey (since diagnosis until present), childhood trauma and a decision-making questionnaire. Data will be analysed intersectionally, employing grounded theory for thematic analysis, sex-based and gender-based analysis and social determinants of health and syndemic framework to understand the experiences of PLHIV in Manitoba. ETHICS AND DISSEMINATION: We received approval from the University of Manitoba Health Ethics Research Board (HS25572; H2022:218), First Nations Health and Social Secretariat of Manitoba, Nine Circles Community Health Centre, Shared Health Manitoba (SH2022:194) and 7th Street Health Access Centre. Findings will be disseminated using community-focused knowledge translation strategies identified by participants, peers, community members and organisations, and reported in conferences, peer-reviewed journals and a website (www.alltogether4ideas.org).

Healthcare utilization among persons living with HIV in Manitoba, Canada, prior to HIV diagnosis: A case-control analysis.

BACKGROUND: Understanding care patterns of persons living with HIV prior to diagnosis can inform prevention opportunities, earlier diagnosis, and engagement strategies. We examined healthcare utilization among HIV-positive individuals and compared them to HIV-negative controls. METHODS: Data were from a retrospective cohort from Manitoba, Canada. Participants included individuals living with HIV presenting to care between 2007 and 2011, and HIV-negative controls, matched (1:5) by age, sex, and region. Data from population-based administrative databases included physician visits, hospitalizations, drug dispensation, and chlamydia and gonorrhea testing. Diagnoses associated with physician visits were classified according to International Classification of Diseases chapters. Conditional logistic regression models were used to compare cases/controls, with adjusted odds ratios (AORs) and their 95% confidence intervals (95% CI) reported. RESULTS: A total of 193 cases and 965 controls were included. Physician visits and hospitalizations were higher for cases, compared to controls. In the 2 years prior to case date, cases were more likely to be diagnosed with "blood disorders" (AOR: 4.2, 95% CI: 2.0-9.0), be treated for mood disorders (AOR: 2.4, 95% CI: 1.6-3.4), and to have 1+ visits to a hospital (AOR: 2.2, 95% CI: 1.4-3.6). CONCLUSION: Opportunities exist for prevention, screening, and earlier diagnosis. There is a need for better integration of healthcare services with public health.

Inguinal Ulceroglandular Tularemia Caused by Francisella tularensis Subspecies holarctica, Canada.

Tularemia is a zoonotic disease caused by the gram-negative coccobacillus Francisella tularensis, a Biosafety Level 3 pathogen and potential agent of bioterrorism. We describe 2 cases of perigenital ulcer disease caused by Francisella tularensis subspecies holarctica in Manitoba, Canada. These cases caused inadvertent exposure among laboratory personnel.

The HIV care cascade in Manitoba, Canada: Methods, measures, and estimates to meet local needs.

BACKGROUND AND OBJECTIVE: We describe the development of the first HIV care cascade for Manitoba, Canada, detailing steps taken to establish indicator definitions for each cascade step, and derive a full complement of local estimates. METHODS: Manitoba is a Canadian Prairie Province with disproportionately high annual HIV incidence. In 2013, a clinical cohort of people living with HIV was established within the primary HIV care program in Manitoba. Using cohort data from 2017, we describe the creation of a set of indicator definitions and calculate estimates for each cascade step to create the first Manitoban cascade model. RESULTS: Of the 703 cohort participants categorized as alive and diagnosed, 638 (90.8%) were in care, 606 (86.2%) retained in care, 573 (81.5%) on treatment, and 523 (74.4%) virologically suppressed. The greatest point of leakage occurred between the first and second steps; 9.3% of those alive and diagnosed in 2017 were not in care in the same calendar year. CONCLUSION: This is the first comprehensive examination of HIV clinical epidemiology in Manitoba using a cascade framework, with the potential inform programming to improve service coverage within Manitoba and significantly contribute to evidence informing provincial policies to support these efforts.

Cohort profile: the LHIV-Manitoba clinical cohort of people living with HIV in Manitoba, Canada.

PURPOSE: The LHIV-Manitoba cohort was developed as a way to provide a comprehensive source of HIV-related health information in the central Canadian Prairie province of Manitoba. The cohort will provide important information as we aim to better understand local HIV epidemiology and address key knowledge and practice gaps in HIV prevention, treatment and care programming in the province. PARTICIPANTS: In total, 890 individuals, aged 18 or older and living or receiving HIV care in Manitoba are enrolled in the cohort. A complete clinical dataset exists for 725 participants, which includes variables on sociodemographic characteristics, comorbidities and co-infections, self-reported HIV exposure categories and HIV clinical indicators. A limited clinical dataset exists for an additional 165 individuals who were enrolled posthumously. 97.5% of cohort participants' clinical records are linked to provincial administrative health datasets. FINDINGS TO DATE: The average age of cohort participants is 49.7 years. Approximately three-quarters of participants are male, 42% self-identified as white and 42% as Indigenous. The majority of participants (64%) reported condomless vaginal sex as a risk exposure for HIV. Nearly one-fifth (18%) of participants have an active hepatitis C virus infection and the cohort's median CD4 count increased from 316 cells/mm3 to 518 cells/mm3 between time of entry into care and end of the first quarter in 2019. FUTURE PLANS: The LHIV-Manitoba cohort is an open cohort, and as such, participant enrolment, data collection and analyses will be continually ongoing. Future analyses will focus on the impact of provincial drug plans on clinical outcomes, determinants of mortality among cohort participants and deriving estimates for a local HIV care cascade.

Rapid CD4 decline prior to antiretroviral therapy predicts subsequent failure to reconstitute despite HIV viral suppression.

HIV-1 infection is characterized by loss of CD4T cells, leading to immunodeficiency. Initiation of antiretroviral therapy (ART) results in suppression of the viral load and increased CD4 counts. Both viral and host factors determine CD4 cell responses to ART with approximately 15-30% of individuals having suboptimal increase of CD4T cell count, most commonly due to lack of compliance to ART. A smaller fraction of patients will have immune reconstitution failure and suboptimal CD4 increase despite suppression of HIV replication, and these individuals are at risk for adverse health outcomes. We sought to characterize the factors associated with decreased immunological response among Manitoba's HIV patient population. This retrospective case-control study included HIV patients with immune reconstitution failure despite suppression of HIV replication by ART. The immune reconstitution failure was defined by CD4 cell count increase from baseline of less than 100 CD4 cells/mm3 or lack of increase to above 200 CD4 cells/mm3 within one year of viral load suppression. Age and nadir CD4 cell counts are known risk factors associated with immune reconstitution failure. We chose controls (Patients with immune reconstitution success) of similar age and CD4 nadir cell with cases (Patients with immune reconstitution failure). We explored the potential effects of gender, HLA type, presence of co-infection, ethnicity, ART type, and rate of pre-treatment CD4 decline among cases and controls. Of more than 550 patients followed by our HIV clinic, 42 individuals met our definition of immune reconstitution failure and they were assigned to the cases group. 31 patients, comprising a range of ages and CD4 nadirs similar to those of the cases, were assigned to the control group. Our primary analysis was a regression model, predicting post-ART change in CD4 over time. After controlling for age and nadir CD4 cell counts, the only potential predictor that appears consistently associated with the rate of post-ART rise in CD4 over time in our cohort, regardless of the other variables that we have controlled for, is the rate of decline in CD4 pre-ART initiation. Several factors have been variably correlated with immune reconstitution failure of CD4 T cell count. Age and low CD4 nadir are factors previously shown to correlate with immune reconstitution failure; and we have controlled for them in our study. Another possible predictor is the rate of decline in CD4 pre-ART, which can serve as an additional marker of reconstitution failure and necessitate prioritizing individuals to ART initiation or identification of a subset of individuals that may be targeted for future adjunct strategies to improve immune recovery.

Characteristics of hospital admissions for pneumonia in HIV-positive individuals in Winnipeg, Manitoba: a cross-sectional retrospective analysis.

Lung infection in human immunodeficiency virus (HIV)-positive individuals remains an important cause of morbidity and mortality, even in the current antiretroviral therapy era. Pneumonia is the most common cause of admission in HIV-positive individuals in our centre as reported in a previously published study. The objective of this retrospective observational study was to further characterize these admissions, with respect to index of disease severity at presentation, organisms identified, and investigations pursued including bronchoalveolar lavage (BAL). There were 123 unique patients accounting for a total of 209 admissions from 2005 to 2015. An organism was isolated in only 33% of all admissions (68/209). The most common organism was Pneumocystis jirovecii with a frequency of 29% of all admissions. Eighty-seven percent of presentations were mild, and 13% were moderate by CURB-65 criteria. A total of 39 BALs were performed, of which 27 yielded an organism (69%). Considering the burden of disease, low diagnostic yield of the current diagnostic strategy and increased morbidity and mortality caused by pneumonia in HIV-positive individuals, further methods are needed to more accurately target therapy. The preponderance of mild disease in this study suggests that better diagnostic tests may identify individuals that can be candidates for outpatient therapy.

Evaluation of the Utility of Point-of-Care HIV Testing on a Canadian Internal Medicine Inpatient Unit.

Point-of-care (POC) HIV testing has been shown to be an acceptable method for increasing HIV testing uptake. To date, no studies have examined the use of POC testing for routine HIV screening on the medicine inpatient unit. A prospective cross-sectional study was conducted over a three-month period in July, August, and October 2016 to evaluate the prevalence of undiagnosed HIV and the attitudes towards routine POC HIV testing. Patients admitted directly to medicine inpatient teaching units at a tertiary hospital in Winnipeg, Canada, were approached for participation. The POC HIV test was administered at the bedside. Reactive and indeterminate tests were confirmed with standard serological HIV testing. Participants were given a questionnaire regarding their attitudes towards POC testing on the unit. Although no cases of previously undiagnosed HIV were identified during the study period, only 35% of participants were found to have ever had HIV testing previously. The majority of participants were satisfied with the POC testing experience and would choose to have the POC testing again. Overall, the low rate of outpatient testing highlights the need for routine HIV testing on an inpatient basis.

The Continuum of HIV Care in Rural Communities in the United States and Canada: What Is Known and Future Research Directions.

The nature of the HIV epidemic in the United States and Canada has changed with a shift toward rural areas. Socioeconomic factors, geography, cultural context, and evolving epidemics of injection drug use are coalescing to move the epidemic into locations where populations are dispersed and health care resources are limited. Rural-urban differences along the care continuum demonstrate the implications of this sociogeographic shift. Greater attention is needed to build a more comprehensive understanding of the rural HIV epidemic in the United States and Canada, including research efforts, innovative approaches to care delivery, and greater community engagement in prevention and care.

Immune Reconstitution Syndrome secondary to Rhodococcus equi infection in a patient with HIV and Burkitt's lymphoma.

Immune Reconstitution Syndrome (IRIS) has been associated with a variety of infections in patients with human immunodeficiency virus (HIV). However, we are reporting the first case of IRIS secondary to Rhodococcus equi (R. equi) in a patient with HIV. We report the case of a 48-year-old male found to have HIV infection in the setting of Burkitt's lymphoma. While on anti-retroviral therapy and chemotherapy, he had developed IRIS secondary to R. equi that manifested as a cavitating pneumonia. This report outlines the successful management of the R. equi infection with the use of a combination of antibiotics, radiographic follow up and suppressive antibiotic while on chemotherapy.

Prior history of testing for syphilis, hepatitis B and hepatitis C among a population-based cohort of HIV-positive individuals and their HIV-negative controls.

Understanding patterns of serological testing for hepatitis B & C, and syphilis among HIV-positive individuals, prior to HIV diagnosis, can inform HIV diagnosis, engagement and prevention strategies. This was a population-based, retrospective analysis of prior serological testing among HIV-positive individuals in Manitoba, Canada. HIV cases were age-, sex- and region-matched to HIV-negative controls at a 1:5 ratio. Conditional logistic regression was used to examine previous serological tests and HIV status. Odds ratios (ORs) and their 95% confidence intervals (95% CI) were reported. A total of 193 cases and 965 controls were included. In the 5 years prior to diagnosis, 50% of cases had at least one test, compared to 26% of controls. Compared to those who did not have serological testing in the 5 years prior to HIV infection, those who had one serological test were at twice the odds of being HIV positive (OR: 1.9, 95% CI: 1.2-2.9), while those with 2 or more tests were at even higher odds (OR: 5.5, 95%CI: 3.7-8.4). HIV cases had higher serological testing rates. Interactions between public health and other healthcare providers should be strengthened.

Systemic inflammation before and after antiretroviral therapy initiation as a predictor of immune response among HIV-infected individuals in Manitoba.

INTRODUCTION: Despite the life-prolonging effects of Highly Active Antiretroviral Therapy (HAART), persons with HIV are still prone to higher rates of non-AIDS related morbidity (such as heart, kidney, and liver disease) than the general public. This is likely due to chronic immune activation and inflammation that persists in HIV-positive persons despite virological suppression. What remains undetermined, however, is whether a link exists between chronic inflammation/immune activation and suboptimal immune recovery on HAART. The hypothesis of the present study is that higher levels of systemic subclinical inflammation and immune activation are linked with suboptimal immune recovery on HAART. METHODS: Fifteen eligible patients from the Manitoba HIV program were enrolled and followed for up to two years; blood samples were drawn at 4 timepoints each, and concentrations of 21 proinflammatory markers were measured. Patients were grouped according to CD4:CD8 recovery at viral suppression, and the inflammatory profiles of the two groups were compared. RESULTS AND CONCLUSIONS: APRIL and BAFF are higher in those with poor recovery at the point of viral suppression, but were also higher in this group at the onset of therapy and through the three additional follow-up visits. TNF-R1, CD163, and Osteopontin, were also in higher concentrations at the outset of therapy and beyond. These five molecules could thus see potential use in the future as biomarkers of likely poor immune recovery. Future work should focus on replicating these findings with larger cohorts.

Substance use and its impact on care outcomes among HIV-infected individuals in Manitoba.

The high prevalence of substance use among HIV-infected individuals creates numerous challenges to patient care. This study was undertaken in order to understand the impact of substance use on care outcomes for HIV-infected individuals in Manitoba. Clinical records of 564 HIV-infected individuals in care at Health Sciences Centre in Winnipeg, Manitoba were reviewed. Clinical data were extracted from patient charts for substance users (illicit substance users, alcohol abusers and chronic users of opioids or benzodiazepines) and non-users. Substance users and non-users were analysed using chi-square analysis and logistic regression models to compare basic socio-demographic and clinic variables. Chi-square and analysis of variance were used to compare a subset of substance users based on similar socio-demographic and clinical characteristics. Among HIV-infected individuals in Manitoba, 38% were substance users with over-representation by Aboriginals, females, young adults and residents of Winnipeg's core areas. Opioids and benzodiazepines were the most commonly used substances with the majority of substance users having used multiple classes of substances in their lifetime. Substance users were more likely than non-users to have missed clinic appointments. Among substance users, missed appointments were more common among those who self-identified as Aboriginal, female, young adults, residents of Winnipeg's core areas, heterosexuals and those who had abused alcohol or cocaine/crack. Aboriginal substance users were also less likely to achieve viral load suppression compared to non-Aboriginal substance users. With the high prevalence of substance use among HIV-infected individuals in Manitoba, it is important to identify at-risk individuals in order to implement appropriate care strategies and improve treatment adherence and health outcomes.

Rapid human immunodeficiency virus disease progression is associated with human leukocyte antigen-B homozygocity and human leukocyte antigen-B51 in a cohort from Manitoba, Canada.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) infection is associated with variable rates of disease progression, influenced by the quality of CD8 T-lymphocyte response, which is determined by human leukocyte antigen (HLA) I alleles. Some individuals progress slowly and maintain viral control, while at the opposite end of the spectrum some individuals endure a faster progression with rapid CD4 decline. We sought to determine the role of HLA-B allele frequency on rapid HIV disease progression. It was hypothesized that rapid progression is associated with the presence of high allele frequency of HLA-B35 and HLA-B homozygocity. METHODS: This retrospective cohort study was conducted in the Manitoba HIV Program, Health Sciences Centre, a tertiary care facility in Winnipeg, Manitoba, Canada. We defined a set of new criteria to describe a subset of individuals with the most rapid HIV disease progression, and collected demographic, clinical, laboratory (CD4 count, viral load) and HLA data on a subset of 20 individuals meeting these criteria. RESULTS: Among those individuals who display extreme rapid progression, an overrepresentation of Aboriginal ethnicities, high frequencies of HLA-B35 and significantly higher rates of HLA-B51, as well as a very high rate of homozygocity for HLA-B alleles, were observed. CONCLUSIONS: Individuals with the most rapid disease progression have higher rates of HLA-B homozygocity, HLA-B51 alleles and higher viral loads than those with normal progression rates. This group, at the extreme end of the spectrum of progression, should be targeted for early treatment.

Relapse of visceral leishmaniasis in an HIV-infected patient successfully treated with a combination of miltefosine and amphotericin B.

The present report documents a 49-year-old HIV-infected man receiving antiretroviral therapy with a suboptimal immune response and a CD4 count of 95 cells/mm(3), despite virological suppression. Investigation of bone marrow was conducted and yielded a diagnosis of visceral leishmaniasis. The clinical course was complicated by gastrointestinal involvment and relapse occurred after amphotericin B therapy. With the addition of miltefosine, the patient no longer presented with bone marrow amastigotes, and displayed an increased CD4 count and negative Leishmania polymerase chain reaction results. The present case highlights atypical presentation of visceral leishmaniasis, including poor immune reconstitution and gastrointestinal involvement. The high likelihood of relapse and response to combination therapy are illustrated.

Le présent rapport rend compte du cas d'un homme de 49 ans atteint du VIH sous antirétroviraux dont la réponse immunitaire était sous-optimale et dont la numération de CD4 était de 95 cellules/mm3, malgré une suppression virologique. L'examen de la moelle osseuse a confirmé un diagnostic de leishmaniose viscérale. L'évolution clinique de la maladie a été compliquée par une atteinte gastro-intestinale, et le patient a fait une rechute après un traitement à l'amphotéricine B. Après l'ajout de miltéfosine, le patient n'avait plus d'amastigotes de la moelle osseuse, présentait une augmentation de la numération de CD4 et des résultats négatifs de Leishmania à la réaction en chaîne par polymérase. Le présent cas fait ressortir la présentation atypique de cette leishmaniose viscérale, y compris la mauvaise reconstitution immunitaire et l'atteinte gastro-intestinale. La forte probabilité de rechute et de réponse à une thérapie combinée est exposée.

Feasibility and success of HIV point-of-care testing in an emergency department in an urban Canadian setting.

BACKGROUND: Approximately 26% of Canadians living with HIV are unaware of their status. Point-of-care (POC) HIV tests have been introduced to simplify and expand HIV testing. OBJECTIVE: To evaluate the feasibility and acceptability of POC testing in an emergency department (ED) setting in Winnipeg, Manitoba. METHODS: A cross-sectional study of unselected adults presenting to the ED at the Health Sciences Centre Hospital (Winnipeg, Manitoba) was performed. Study procedures included pre- and post-test counselling, administration of the INSTI HIV-1/HIV-2 Antibody Test (bioLytical Laboratories, Canada) and a brief questionnaire. Venous blood samples were collected from participants for confirmatory testing on all reactive and indeterminate specimens. RESULTS: In total, 501 adults participated in the study. The majority of participants were younger than 40 years of age, approximately one-half (48.5%) were women and 53% self-identified as Aboriginal. Nearly one-half (49.1%) of the participants had undergone previous HIV testing, although 63% of these tests were performed more than a year earlier. A total of seven individuals tested reactive with the POC test, all of whom were confirmed positive using serological testing (1.4%) and were linked to an HIV specialist within 24 h. Nearly all of the participants (96%) reported satisfaction with the test and believed it belonged in the ED (93%). CONCLUSIONS: Of the participants tested, 1.4% tested reactive for HIV, which is significantly higher than the reported prevalence in Manitoba and in other similar studies conducted in North America. Furthermore, all individuals were linked to timely care. The present study demonstrated that this particular busy tertiary care ED is an important and feasible location for HIV POC testing.

INTRODUCTION: Environ 26 % des Canadiens qui sont atteints du VIH ne connaissent pas leur statut. Les tests du VIH au point de service (PDS) ont créés pour simplifier et généraliser le test du VIH. OBJECTIF: Évaluer la faisabilité et l'acceptabilité du test au PDS au sein d'une urgence de Winnipeg, au Manitoba. MÉTHODOLOGIE: Les chercheurs ont procédé à une étude transversale auprès d'adultes non sélectionnés qui se sont présentés à l'urgence du Health Sciences Centre Hospital de Winnipeg, au Manitoba. Pendant l'étude, les interventions incluaient des conseils avant et après le test, l'administration du test INSTI de recherche des anticorps anti-VIH-1/VIH-2 (bioLytical Laboratories, Canada) et un bref questionnaire. Ils ont prélevé du sang veineux pour effectuer un test de confirmation sur tous les échantillons réactifs ou indéterminés. RÉSULTATS: Au total, 501 adultes ont participé à l'étude. La majorité avaient moins de 40 ans, environ la moitié (48,5 %) étaient des femmes et 53 % ont eux-mêmes précisé qu'ils étaient des Autochtones. Près de la moitié (49 %) avaient déjà subi un test du VIH, mais 63 % de ces tests avaient été exécutés plus d'un an auparavant. Au total, sept personnes étaient réactives au test au PDS, toutes confirmées comme positives au test sérologique (1,4 %) et ont été orientées vers un spécialiste du VIH dans les 24 heures. Presque tous les participants (96 %) se sont dits satisfaits du test et pensaient qu'il était caractéristique de l'urgence (93 %). CONCLUSIONS: Sur les participants qui ont subi le dépistage, 1,4 % était réactif au VIH, ce qui est considérablement plus élevé que la prévalence déclarée au Manitoba et dans d'autres études similaires d'Amérique du Nord. De plus, toutes les personnes ont été orientées rapidement vers des soins. La présente étude a démontré que cette urgence de soins tertiaires achalandée est un lieu important et faisable comme PDS pour effectuer le test du VIH.

HIV controllers are distinguished by chemokine expression profile and HIV-specific T-cell proliferative potential.

BACKGROUND: HIV controllers demonstrate a natural ability to control HIV replication in the absence of antiretroviral therapy. We performed a comprehensive evaluation of inflammation and T-cell activation in a demographically unique cohort of HIV controllers and noncontrollers. METHODS: Plasma concentrations of 22 cytokines and chemokines were evaluated using a multiplex bead array approach. Multicolor flow cytometry was used to measure baseline levels of T-cell activation and regulatory T cells (Tregs) and HIV-specific T-cell cytokine (interferon γ, interleukin 2) and proliferation responses. RESULTS: HIV controllers were characterized by elevated macrophage inflammatory protein 1α and low levels of interferon γ-induced protein 10, monocyte chemotactic protein 1, and Transforming growth factor beta. Activated (CD38(+) HLA DR(+)) CD4(+) and CD8(+) T cells were reduced in HIV controllers relative to noncontrollers. HIV controllers and noncontrollers had comparable proportions of Tregs within the CD4(+) T-cell compartment, but absolute Treg counts were depleted in noncontrollers. Absolute Treg counts correlated inversely with T-cell activation. Proliferative CD4(+) and CD8(+) T-cell responses directed against HIV gag epitopes were found most frequently among HIV controllers with the lowest viral loads (elite controllers) and were rarely detected among noncontrollers, supporting a relationship between HIV-specific T-cell proliferation and viral control. CONCLUSIONS: Collectively, these data suggest a model in which HIV controllers maintain low levels of viral replication through robust HIV-specific T-cell responses in an environment of low inflammation and reduced availability of activated target cells.