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Clinical Sciences Oral Abstract Session #1

Tracks
Track 2
Friday, April 28, 2023
11:00 - 12:30
Room 205AB

Overview

Sciences cliniques séances de présentation orale d’abrégés #1


Speaker

Marina Klein
Professor Of Medicine
Mcgill University Health Centre Research Institute

The Rate of Hepatitis C Virus (HCV) Reinfection in Canadians Coinfected with HIV and its Implications for National Elimination

Abstract

Background: The World Health Organisation (WHO) set a target of ≤2 new HCV infections/100 person-years (PY) in people who inject drugs (PWID), as a way to measure progress towards HCV elimination. As more people are successfully treated for HCV, an increasing proportion of new infections will be reinfections. We consider whether the reinfection rate has changed since the interferon era in Canadians coinfected with HIV.

Methods: The Canadian Coinfection Cohort is representative of HIV/HCV coinfected people in clinical care. We selected cohort participants first successfully treated for a primary HCV infection in either the interferon or direct acting antiviral (DAA) treatment eras. Participants were followed from 12 weeks after completing treatment until the end of 2019 or their last measured HCV RNA. We estimated the reinfection rate in each era using piecewise exponential proportional hazard models.

Results: Among 814 successfully treated participants with additional HCV RNA measurements, there were 62 reinfections. The overall reinfection rate was 2.6/100 PY in the interferon era and 3.4/100 PY in the DAA era (Table). The rate in those reporting injection drug use during follow-up was much higher: 4.7 and 7.6/100 PY in the interferon and DAA eras, respectively.

Conclusions: The reinfection rate in our cohort is now above the WHO target and has increased in PWID since the interferon era. Given coinfected PWID are more likely to be in care – and to have a lower reinfection rate – than other PWID, this suggests Canada is not on track to eliminate HCV by 2030.
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Yves Fougère
Pediatric Infectious Disease Fellow
CHU Sainte-Justine

CMV co-infection among children living with HIV in Canada is associated with more frequent HIV viremia and lower CD4/CD8 nadir.

Abstract

Background: There is evidence that CMV co-infection among people living with HIV is associated with chronic inflammation and HIV disease progression. Paediatric studies are limited compared to those of adults, particularly outside of resource-limited settings. Our objective was to characterize CMV co-infection among Canadian children living with perinatally acquired HIV (CLWH) and determine the association between CMV viremia and HIV control.

Methods: Sub-study of the prospective, multicenter Early Pediatric Initiation Canada Child Cure Cohort study (EPIC4). CLWH were followed every 3-6 months from 2014–2018. CMV serostatus (IgG) was determined at baseline visit and end of study for those seronegative at baseline, and CMV and HIV viral loads (VL) and lymphocyte subsets were quantified at every visit for those with IgG seropositivity.

Results: 225 CLWH were enrolled with median baseline age of 13.9 years (IQR, 9.3-17.0 years); 121 (53.8%) were female and median follow up was 32 months (IQR, 21-38). 192 (85.3%) were CMV seropositive at baseline (5 with documented congenital CMV). CMV seropositivity was significantly higher among foreign vs Canadian born children (62.5 vs. 18.2%, p<0.01). Thirty-four (17.7%) CMV seropositive CLWH were CMV viremic at least once during follow-up (CMV VL range 85-1991 international units/mL). Though there was no difference in median age of cART initiation (3.7 vs 4.4 years, p=0.15) or incidence of treatment interruptions during follow-up (14.7% vs 8.2%, p=0.40) in those with and without CMV viremia, those with CMV viremia were more likely to have at least one episode of detectable HIV VL (64.7% vs 33.5%, p< 0.001), and to have lower CD4/CD8 nadir (0.68 vs. 0.83 p=0.043).

Conclusion: Among CLWH in Canada, CMV viremia is common and associated with HIV viremia and lower nadir CD4/CD8 ratio. Further work is necessary to determine the potential role of CMV in HIV disease progression and chronic inflammation among children.
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Sofia Levy
University of British Columbia

Burden of Chronic/Latent Viral Infections and Estimated All-Cause Mortality Risk in Women Living With HIV and HIV-Negative Controls in the BCC3 Study

Abstract

Background: Women living with HIV (WLWH) in Canada have a shorter life expectancy than both men living with HIV and HIV-negative women. Latent/chronic viral infections may increase inflammation, which could affect health outcomes for WLWH. We compared the prevalence of several chronic/latent viral infections between WLWH and HIV-negative women and investigated the association between the burden of viral infections and estimated mortality risk.
Methods: BCC3 is a study of women’s healthy aging enrolling WLWH and controls (trans-inclusive) ≥16y. Prevalence of eight chronic/latent viral infections (Table 1) was determined by serology or self-report (VZV only). The Veteran’s Aging Cohort Study 2.0 (VACS 2.0) estimating 5-year all-cause mortality risk was calculated based on survey data and laboratory results. Statistical analyses employed Mann-Whitney test, Spearman’s correlation, and logistic regression.
Results: WLWH were older than controls and had higher age-adjusted prevalence of 4/8 viruses (CMV, EBV, HSV-2, and HBV), while controls were more likely to harbor HHV-8 (Table 1). WLWH had both a higher median [IQR] burden of viral infections (5 [4-5] vs 4 [3-5]) and VACS 2.0 score (8 [5-22] vs 3 [2-5] %) compared to controls, both p<0.0001. Viral burden was associated with estimated all-cause mortality risk for both WLWH (rho=0.38, p<0.0001) and controls (rho=0.41, p<0.0001).
Conclusions: While a causal relationship cannot be implied between having more chronic/viral infections and 5-year risk of mortality, these data highlight the potential influence of non-HIV latent viruses, some highly prevalent, that could play an important role in the inflammaging/aging and lifespan of WLWH.
Wesal Elgretli
Master Student
McGill University

The Effect of Hepatic Steatosis and Fibrosis on Cardiovascular Disease Risk in Patients with Hepatitis C

Abstract


Background. Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common cause of chronic liver disease worldwide, with a prevalence at 25%, with a higher prevalence in people living with the hepatitis C virus (HCV) (45–55%). Both MAFLD and HCV are linked with an increased risk of cardiovascular disease (CVD). We aimed to determine whether hepatic steatosis and liver fibrosis are associated with increased CVD risk in people with HCV.

Methods. This was a retrospective study including people living with HCV consecutively screened for hepatic steatosis and fibrosis by Fibroscan at a single centre. Hepatic steatosis and significant liver fibrosis were defined as controlled attenuation parameter (CAP) ≥275 dB/m and liver stiffness measurement (LSM) ≥8 kPa, respectively. CVD risk was assessed using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score. A linear regression modelling adjusted for confounders was used to identify ASCVD risk variables.

Results. 155 patients with HCV (mean age 60 years, 44% male, 30% with undetectable HCV viral load). Hepatic steatosis and significant liver fibrosis were found in 25% and 48% of patients, respectively. The prevalence of low, borderline, intermediate, and high ASCVD risk was 38%, 10%, 20%, and 32%, respectively. Prevalence of intermediate-high ASCVD risk categories was higher in patients with hepatic steatosis vs those without (59% vs 47%, p<0.05), and in patients with significant liver fibrosis vs those without (57% vs 45%, p<0.01). On linear regression analysis, both CAP (regression coefficient 0.03, 95% CI 0.001-0.06) and LSM (regression coefficient 0.14, 95% CI 0.01-0.32) were independently associated with ASCVD risk score after adjusting for liver transaminases and BMI.

Conclusions. Hepatic steatosis and significant liver fibrosis are associated with increased ASCVD risk in people living with HCV. Cardiovascular disease should be assessed in patients with HCV and with hepatic steatosis and/or liver fibrosis.
Katherine Kooij
postdoctoral fellow
BC Centre for Excellence in HIV/AIDS

A Comparative Study of Nonfatal Overdoses in People With and Without HIV in British Columbia, Canada

Abstract

Background: The magnitude of the drug toxicity crisis is most severe in British Columbia (BC) and people with HIV (PWH) are disproportionately affected. Nonfatal overdoses (NFODs) are associated with increased mortality in the following year; more insight is needed into the occurrence, determinants, and consequences of NFODs among PWH.

Methods: The Comparative Outcomes and Service Utilization Trends study is a population-based cohort linking demographic and clinical data from the BC Centre for Excellence in HIV/AIDS with administrative data from Population Data BC on all PWH in BC and a 10% general population sample, aged ≥19 years. We assessed and compared the age-adjusted incidence rate (IR) of NFOD events resulting in hospitalization or acute care visit, between men and women with and without HIV. Using Poisson regression, we modelled the interaction between sex and HIV-status.

Results: Between 2012-2020, 11,062 PWH (81.8% male) and 474,072 people without HIV (50.3% male) were followed-up for a median of 7.9 (Q1-Q3:7.3-7.9) and 7.9 years (Q1-Q3:4.3-7.9) years respectively. Age-adjusted IRs among men with and without HIV were 40 (95%CI:38-43) and 3.4 (95%CI:3.3-3.5)/1000 PY, IRR=11.8 (95%CI:11.0-12.6), and for women with and without HIV 69 (95%CI:63-74) and 2.7 (95%CI:2.6-2.7)/1000 PY, IRR=25.8 (95%CI:23.7-27.9). Between 2013-2019, the age-adjusted NFOD rate statistically significantly increased among men and women without HIV but not among PWH. After adjusting for age and neighbourhood-level income quintile, HIV remained significantly associated with a higher NFOD rate (IRR=12.7, 95%CI:11.8-13.7). Compared to men without HIV, the NFOD rate in women without HIV was lower (IRR=0.8) whereas it was higher in men (IRR=10.2) and women with HIV (IRR=17.3)(p-interaction<0.001).

Conclusions: These preliminary results demonstrate a significantly higher NFOD rate among PWH compared to people without HIV. The NFOD rate was highest among women with HIV. These findings stress the need for policies and programs oriented toward PWH to mitigate overdoses.
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Kirsten Hall
Medical Student
University Of Saskatchewan

HIGH PANDEMIC-RELATED MORTALITY AMONGST PEOPLE WITH HIV IN SASKATCHEWAN, CANADA

Abstract

Background

Saskatchewan faces an HIV epidemic driven by injection drug use (IDU) with disproportionate representation of younger persons, women, and Indigenous persons. HIV incidence in Saskatchewan in 2021 was 4.5 times the Canadian average.

During COVID-19, the use of synthetic fentanyl surged, leading to high overdose events & deaths.

We characterized the difference in HIV cascade of care outcomes & mortality amongst people with HIV (PWH) in southern Saskatchewan during the pandemic.

Methods

We conducted a retrospective cohort study for all PWH cared for in the Infectious Diseases Clinic (IDC) in Regina between December 31/19 and June 10/22. Age, sex, ethnicity & primary mode of HIV acquisition, cascade of care and mortality data were collected from the IDC database. All deaths along with most likely cause were determined via case review.

Results

On December 31/19 and June 10/22 respectively, IDC cared for 518 and 585 PWH. Amongst the current cohort, 245 (42%) were female, 163 (28%) were ≤ 35 years, 306 (52%) were Indigenous, and 318 (54%) acquired HIV through IDU.

Cascade measures worsened during COVID-19. 58.1% were retained in care & 76.1% virally suppressed (HIV RNA ≤ 200 copies/mL) in December 2019, decreasing to 51.3% (p=0.02) & 68.8% (p=0.06) by June 2022.

80 deaths occurred during the study period, 15.4% of the cohort from December 2019. Most (49, 61.3%) were due to suspected or confirmed overdose. 10 (12.5%) occurred due to complications from IDU. No deaths were directly attributable to COVID-19. Most who died acquired HIV from IDU (69/80, 86%).

Conclusions

We describe intersecting epidemics of HIV and IDU leading to significant morbidity & mortality in high-risk populations during COVID-19. Contributing factors may be disruption of safe supply & harm reduction services. Comprehensive harm reduction and addiction management are needed to reduce morbidity & mortality amongst PWH in Saskatchewan.
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