A two-day workshop reviewing Canadian provincial and national HIV care cascade indicators, reporting, challenges, and recommendations.

BACKGROUND: The HIV care cascade is an indicators-framework used to assess achievement of HIV clinical targets including HIV diagnosis, HIV care initiation and retention, initiation of antiretroviral therapy, and attainment of viral suppression for people living with HIV. METHODS: The HIV Care Cascade Research Development Team at the CIHR Canadian HIV Trials Network Clinical Care and Management Core hosted a two-day virtual workshop to present HIV care cascade data collected nationally from local and provincial clinical settings and national cohort studies. The article summarizes the workshop presentations including the indicators used and available findings and presents the discussed challenges and recommendations. RESULTS: Identified challenges included (1) inconsistent HIV care cascade indicator definitions, (2) variability between the use of nested UNAIDS's targets and HIV care cascade indicators, (3) variable analytic approaches based on differing data sources, (4) reporting difficulties in some regions due to a lack of integration across data platforms, (5) lack of robust data on the first stage of the care cascade at the sub-national level, and (6) inability to integrate key socio-demographic data to estimate population-specific care cascade shortfalls. CONCLUSION: There were four recommendations: standardization of HIV care cascade indicators and analyses, additional funding for HIV care cascade data collection, database maintenance and analyses at all levels, qualitative interviews and case studies characterizing the stories behind the care cascade findings, and employing targeted positive-action programs to increase engagement of key populations in each HIV care cascade stage.

HISTORIQUE: La cascade des soins du VIH est un cadre d'indicateurs utilisé pour évaluer l'atteinte des cibles cliniques du VIH, y compris le diagnostic, le début et le maintien des soins, le début du traitement antirétroviral et l'obtention de la suppression virale chez les personnes qui vivent avec le VIH. MÉTHODOLOGIE: L'équipe de développement de la recherche sur la cascade des soins du VIH située au noyau de perfectionnement de la gestion clinique du Réseau canadien pour les essais VIH des IRSC a organisé un atelier virtuel de deux jours pour présenter les données sur la cascade des soins du VIH amassées dans les milieux cliniques locaux et provinciaux et les études de cohorte de tout le pays. L'article résume les présentations d'ateliers, y compris les indicateurs utilisés et les observations disponibles, et présente les défis et recommandations abordés. RÉSULTATS: Les défis mis en évidence incluaient 1) les définitions hétérogènes des indicateurs de la cascade des soins sur le VIH, 2) la variabilité entre l'utilisation des cibles d'ONUSIDA imbriquées et les indicateurs de cascade des soins du VIH, 3) des approches analytiques variables d'après diverses sources de données, 4) la déclaration des difficultés dans certaines régions à cause de l'absence d'intégration entre les plateformes de données, 5) l'absence de données vigoureuses sur la première étape de la cascade des soins infranationaux et 6) l'incapacité d'intégrer les principales données sociodémographiques pour évaluer les écueils de la cascade des soins populationnels. CONCLUSION: Quatre recommandations ont été formulées : la standardisation des indicateurs et des analyses de la cascade des soins du VIH, le financement supplémentaire de la collecte de la cascade des soins du VIH, l'entretien des bases de données et les analyses à tous les échelons, les entrevues qualitatives et les études de cas qui caractérisent les histoires qui se cachent derrière les observations tirées de la cascade des soins et le recours à des programmes d'action positive ciblés pour accroître la participation de populations clés à chaque étape de la cascade des soins du VIH.

Apples to Apples? A Comparison of Real-World Tolerability of Antiretrovirals in Patients with Human Immunodeficiency Virus Infection and Patients with Primary Biliary Cholangitis.

We previously characterized a human betaretrovirus and linked infection with the development of primary biliary cholangitis (PBC). There are in vitro and in vivo data demonstrating that antiretroviral therapy used to treat human immunodeficiency virus (HIV) can be repurposed to treat betaretroviruses. As such, PBC patients have been treated with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), alone and in combination with a boosted protease inhibitor or an integrase strand transfer inhibitor in case studies and clinical trials. However, a randomized controlled trial using combination antiretroviral therapy with lopinavir was terminated early because 70% of PBC patients discontinued therapy because of gastrointestinal side effects. In the open-label extension, patients tolerating combination therapy underwent a significant reduction in serum liver parameters, whereas those on NRTIs alone rebounded to baseline. Herein, we compare clinical experience in the experimental use of antiretroviral agents in patients with PBC with the broader experience of using these agents in people living with HIV infection. While the incidence of gastrointestinal side effects in the PBC population appears somewhat increased compared to those with HIV infection, the clinical improvement observed in patients with PBC suggests that further studies using the newer and better tolerated antiretroviral agents are warranted.

Differential Signature of the Microbiome and Neutrophils in the Oral Cavity of HIV-Infected Individuals.

HIV infection is associated with a wide range of changes in microbial communities and immune cell components of the oral cavity. The purpose of this study was to evaluate the oral microbiome in relationship to oral neutrophils in HIV-infected compared to healthy individuals. We evaluated oral washes and saliva samples from HIV-infected individuals (n=52) and healthy controls (n=43). Using 16S-rRNA gene sequencing, we found differential ß-diversity using Principal Coordinate Analysis (PCoA) with Bray-Curtis distances. The α-diversity analysis by Faith's, Shannon, and observed OTUs indexes indicated that the saliva samples from HIV-infected individuals harbored significantly richer bacterial communities compared to the saliva samples from healthy individuals. Notably, we observed that five species of Spirochaeta including Spirochaetaceae, Spirochaeta, Treponema, Treponema amylovorum, and Treponema azotonutricum were significantly abundant. In contrast, Helicobacter species were significantly reduced in the saliva of HIV-infected individuals. Moreover, we found a significant reduction in the frequency of oral neutrophils in the oral cavity of HIV-infected individuals, which was positively related to their CD4+ T cell count. In particular, we noted a significant decline in CD44 expressing neutrophils and the intensity of CD44 expression on oral neutrophils of HIV-infected individuals. This observation was supported by the elevation of soluble CD44 in the saliva of HIV-infected individuals. Overall, the core oral microbiome was distinguishable between HIV-infected individuals on antiretroviral therapy compared to the HIV-negative group. The observed reduction in oral neutrophils might likely be related to the low surface expression of CD44, resulting in a higher bacterial diversity and richness in HIV-infected individuals.

Bartonella quintana infective endocarditis in northern Alberta: A case report.

We present a case of Bartonella quintana infective endocarditis requiring valvular surgery in an Indigenous patient from northern Alberta that was identified months after initial presentation to hospital with undifferentiated laboratory abnormalities. Syndromes caused by B. quintana are often challenging to diagnose due to their non-specific presentation and the difficulty in detecting this organism using traditional culture methods. Additionally, risk factors for B. quintana include marginal housing and alcohol use disorder, which often impede access to health care. Indigenous patients in northern Canada often face worse health outcomes compared with other regions owing to poor economic conditions, substandard housing, and limited access to health care resources. Given that risk factors for B. quintana are prevalent throughout northern Canada and that this infection is difficult to diagnose, we surmise that the prevalence of B. quintana infection is underestimated in northern Canada.

Les auteurs présentent un cas d'endocardite infectieuse à Bartonella quintana exigeant une chirurgie valvulaire chez un patient autochtone du nord de l'Alberta, dépisté des mois après la première consultation à l'hôpital, alors que les anomalies de laboratoires étaient indifférenciées. Les syndromes causés par le Bartonella quintana sont souvent difficiles à diagnostiquer à cause de leur présentation non spécifique et de la difficulté à déceler cet organisme au moyen des méthodes de culture classiques. De plus, les facteurs de risque de Bartonella quintana incluent des logements inférieurs aux normes et des troubles de l'usage de l'alcool, qui nuisent souvent à l'accès aux soins. Les patients autochtones du nord du Canada présentent souvent des résultats cliniques pires que ceux d'autres régions à cause des mauvaises conditions économiques, des logements inférieurs aux normes et de l'accès limité aux ressources de santé. Puisque les facteurs de risque de Bartonella quintana prévalent dans tout le nord du Canada et que cette infection est difficile à diagnostiquer, les auteurs postulent que la prévalence d'infection à Bartonella quintana est sous-estimée dans cette région.

What determines do-not-resuscitate status in critically ill HIV-infected patients admitted to ICU?

PURPOSE: To identify factors associated with do-not-resuscitate (DNR) status in critically ill patients infected with human immunodeficiency virus (HIV) admitted to the Intensive Care Unit (ICU) in the era of combination antiretroviral therapy (cART). MATERIALS AND METHODS: Retrospective cohort study of first-time admissions of HIV-infected patients to ICUs in Edmonton, Alberta, from 2002 to 2014. Multivariable logistic regression analysis was performed to identify factors associated with DNR status. RESULTS: There were 282 HIV-infected patients with first-time ICU admissions, with an incidence rate of 6.6 per 1000 ICU admissions. Sixty-seven (24%) patients had a DNR designation and support was withdrawn in 37 (13%). In multivariable analysis, APACHE II score (OR 1.13; 95% CI, 1.08-1.19, p < 0.001), coronary artery disease (OR 5.70; 95% CI, 1.18-27.76, p = 0.031), prior opportunistic infection (OR 2.59; 95% CI, 1.20-5.57, p = 0.015) and duration of HIV infection (OR 1.07 per year; 95% CI, 1.01-1.14, p = 0.025) were independently associated with DNR status. Ethnicity, HIV risk factors, CD4 count and viral load were not associated with DNR status. CONCLUSIONS: One in four patients had a DNR designation. Illness acuity, selected comorbidity, previous opportunistic infection and HIV duration were associated with DNR designation.

An unusual case of Erysipelothrix rhusiopathiae prosthetic joint infection from the Canadian Arctic: whole genome sequencing unable to identify a zoonotic source.

BACKGROUND: Erysipelothrix rhusiopathiae is a zoonotic pathogen that causes erysipeloid and is most frequently associated with exposure to domestic swine. Infection of native and prosthetic joints is a rarely reported manifestation. CASE PRESENTATION: We describe a case of E. rhusiopathiae prosthetic joint infection in a woman with a history of exposure to wild animals in the Canadian Arctic. Patient management involved a 1-stage surgical revision exchange with an antibiotic impregnated cement spacer and 6 weeks of intravenous penicillin G followed by 6 weeks of oral amoxicillin. Ten previously reported cases of E. rhusiopathiae joint infection are reviewed. Recent increases in mortality due to infection with this organism among host animal populations in the Canadian Arctic have generated concern regarding a potential increase in human infections. However, whole genome sequencing (WGS) of the organism was unable to identify a zoonotic origin for this case. CONCLUSIONS: Consideration should be given to E. rhusiopathiae as a cause of joint infections if the appropriate epidemiologic and host risk factors exist. Expanded use of WGS in other potential animal hosts and environmental sources may provide important epidemiologic information in determining the source of human infections.

Mycobacterium branderi infection: Case report and literature review of an unusual and difficult-to-treat non-tuberculous mycobacterium.

A 67-year-old man with significant smoking history presented with fever, unintentional weight loss, night sweats, productive cough, and progressive dyspnea. Multiple respiratory specimens grew Mycobacterium branderi. Computed tomography scanning of the chest revealed a cavitary right upper lung lesion. Bronchoscopy and thoracoscopic biopsy were negative for malignancy but showed necrotizing granulomatous inflammation, which was culture negative. Due to clinical and radiologic progression despite therapy with clarithromycin, ethambutol and moxifloxacin, the lesion was surgically resected and the patient's symptoms resolved. Mycobacteria were seen in histopathology but did not grow from resected tissue. The patient received an additional 6 months of medical therapy and remains asymptomatic 1 month after completing antimicrobials. Cases of M. branderi causing human infection are very rarely reported. This is a novel case of multi-drug resistant M. branderi pulmonary infection in an apparently immunocompetent patient, progressive despite medical therapy and requiring surgical resection for definitive management.

Epidemiology and Outcomes in Critically Ill Patients with Human Immunodeficiency Virus Infection in the Era of Combination Antiretroviral Therapy.

Purpose. The impact of critical illness on survival of HIV-infected patients in the era of antiretroviral therapy remains uncertain. We describe the epidemiology of critical illness in this population and identify predictors of mortality. Materials and Methods. Retrospective cohort of HIV-infected patients was admitted to intensive care from 2002 to 2014. Patient sociodemographics, comorbidities, case-mix, illness severity, and 30-day mortality were captured. Multivariable Cox regression analyses were performed to identify predictors of mortality. Results. Of 282 patients, mean age was 44 years (SD 10) and 169 (59%) were male. Median (IQR) CD4 count and plasma viral load (PVL) were 125 cells/mm3 (30-300) and 28,000 copies/mL (110-270,000). Fifty-five (20%) patients died within 30 days. Factors independently associated with mortality included APACHE II score (adjusted hazard ratio [aHR] 1.12; 95% CI 1.08-1.16; p < 0.001), cirrhosis (aHR 2.30; 95% CI 1.12-4.73; p = 0.024), coronary artery disease (aHR 6.98; 95% CI 2.20-22.13; p = 0.001), and duration of HIV infection (aHR 1.07 per year; 95% CI 1.02-1.13; p = 0.01). CD4 count and PVL were not associated with mortality. Conclusions. Mortality from an episode of critical illness in HIV-infected patients remains high but appears to be driven by acute illness severity and HIV-unrelated comorbid disease rather than degree of immune suppression.

Are forested buffers an effective conservation strategy for riparian fauna? An assessment using meta-analysis.

Historically, forested riparian buffers have been created to provide protection for aquatic organisms and aquatic ecosystem functions. Increasingly, new and existing riparian buffers are being used also to meet terrestrial conservation requirements. To test the effectiveness of riparian buffers for conserving terrestrial fauna, we conducted a meta-analysis using published data from 397 comparisons of species abundance in riparian buffers and unharvested (reference) riparian sites. The response of terrestrial species to riparian buffers was not consistent between taxonomic groups; bird and arthropod abundances were significantly greater in buffers relative to unharvested areas, whereas amphibian abundance decreased. Edge-preferring species were more abundant in buffer sites than reference sites, whereas species associated with interior habitat were not significantly different in abundance. The degree of buffer effect on animal abundance was unrelated to buffer width; wider buffers did not result in greater similarity between reference and buffer sites. However, responses to buffer treatment were more variable in buffers <50 m wide, a commonly prescribed width in many management plans. Our results indicate that current buffer prescriptions do not maintain most terrestrial organisms in buffer strips at levels comparable to undisturbed sites.