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Introduction: People living with HIV (PLWH) and/or who inject drugs may experience lower vaccine effectiveness (VE) against SARS‐CoV‐2 infection. Methods: A validated algorithm was applied to population‐based, linked administrative datasets in the British Columbia COVID‐19 Cohort (BCC19C) to ascertain HIV status and create a population of PLWH and matched HIV‐negative individuals. The study population was limited to individuals who received an RT‐PCR laboratory test for SARS‐CoV‐2 between 15 December 2020 and 21 November 2021 in BC, Canada. Any history of injection drug use (IDU) was ascertained using a validated administrative algorithm. We used a test‐negative study design (modified case−control analysis) and multivariable logistic regression to estimate adjusted VE by HIV status and history of IDU. Results: Our analysis included 2700 PLWH and a matched population of 375,043 HIV‐negative individuals, among whom there were 351 and 103,049 SARS‐CoV‐2 cases, respectively. The proportion of people with IDU history was much higher among PLWH compared to HIV‐negative individuals (40.7% vs. 4.3%). Overall VE during the first 6 months after second dose was lower among PLWH with IDU history (65.8%, 95% CI = 43.5–79.3) than PLWH with no IDU history (80.3%, 95% CI = 62.7–89.6), and VE was particularly low at 4–6 months (42.4%, 95% CI = −17.8 to 71.8 with IDU history vs. 64.0%; 95% CI = 15.7–84.7 without), although confidence intervals were wide. In contrast, overall VE was 88.6% (95% CI = 88.2–89.0) in the matched HIV‐negative population with no history of IDU and remained relatively high at 4–6 months after second dose (84.6%, 95% CI = 83.8–85.4). Despite different patterns of vaccine protection by HIV status and IDU history, peak estimates were similar (≥88%) across all populations. Conclusions: PLWH with a history of IDU may experience lower VE against COVID‐19 infection, although findings were limited by a small sample size. The lower VE at 4–6 months may have implications for booster dose prioritization for PLWH and people who inject drugs. The immunocompromising effect of HIV, substance use and/or co‐occurring comorbidities may partly explain these findings. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatitis C virus (HCV) reinfection among high‐risk groups threatens HCV elimination goals. We assessed HCV reinfection rates among men who have sex with men (MSM) in British Columbia (BC), Canada. Methods: We used data from the BC Hepatitis Testers Cohort, which includes nearly 1.7 million individuals tested for HCV or HIV in BC. MSM who had either achieved sustained virologic response (SVR) after successful HCV treatment, or spontaneous clearance (SC) and had ≥1 subsequent HCV RNA measurement, were followed from the date of SVR or SC until the earliest of reinfection, death, or last HCV RNA measurement. Predictors of reinfection were identified by Cox proportional modelling. The earliest study start date was 6 November 1997 and latest end date was 13 April 2018. Results: Of 1349 HCV‐positive MSM who met the inclusion criteria, 493 had SC while 856 achieved SVR. 349 (25.65%) had HIV coinfection. We identified 98 reinfections during 5203 person‐years (PYs) yielding a reinfection rate of 1.88/100PYs. The reinfection rate among SC (2.74/100PYs) was more than twice that of those with SVR (1.03/100 PYs). Problematic alcohol use (aHR 1.73, 95% CI 1.003‐2.92), injection drug use (aHR 2.60, 95% CI 1.57‐4.29) and HIV coinfection (aHR 2.04, 95% CI 1.29‐3.23) were associated with increased risk of HCV reinfection. Mental health counselling history (aHR 0.24, 95% CI 0.13‐0.46) was associated with reduced HCV reinfection risk. Conclusions: There is the need to engage MSM in harm reduction and prevention services following treatment to reduce reinfection risk. [ABSTRACT FROM AUTHOR]

Introduction: Identifying appropriate pre‐exposure prophylaxis (PrEP) candidates is a challenge in planning for the safe and effective roll‐out of this strategy. We explored the use of a validated HIV risk screening tool, HIV Incidence Risk Index for Men who have Sex with Men (HIRI‐MSM), to identify “optimal” candidates among MSM testing at a busy sexual health clinic's community testing sites in Toronto, Canada. Methods: Between November 2014 and April 2015, we surveyed MSM undergoing anonymous HIV testing at community testing sites in Toronto, Canada, to quantify “optimal” candidates for scaling up PrEP roll‐out, defined as being at high objective HIV risk (scoring ≥10 on the HIRI‐MSM), perceiving oneself at moderate‐to‐high HIV risk and being willing to use PrEP. Cascades were constructed to identify barriers to broader PrEP uptake. The association between HIRI‐MSM score and both willingness to use PrEP and perceived HIV risk were explored in separate multivariable logistic regression analyses. Results: Of 420 respondents, 64.4% were objectively at high risk, 52.5% were willing to use PrEP and 27.2% perceived themselves at moderate‐to‐high HIV risk. Only 16.4% were “optimal” candidates. Higher HIRI‐MSM scores were positively associated with both willingness to use PrEP (aOR=1.7 per 10 score increase, 95%CI=1.3–2.2) and moderate‐to‐high perceived HIV risk (aOR=1.7 per 10 score increase, 95%CI=1.2–2.3). The proportion of men who were “optimal” candidates increased to 42.9% when the objective HIV risk cut‐off was changed to top quartile of HIRI‐MSM scores (≥26). In our full cascade, a very low proportion (5.3%) of MSM surveyed could potentially benefit from PrEP under current conditions. The greatest barrier in the cascade was low perception of HIV risk among high‐risk men, but considerable numbers were also lost in downstream cascade steps. Of men at high objective HIV risk, 68.3% did not perceive themselves to be at moderate‐to‐high HIV risk, 23.6% were unaware of PrEP, 40.1% were not willing to use PrEP, 47.6% lacked a family physician with whom they felt comfortable discussing sexual health, and 31.6% had no means to cover the cost of PrEP. Conclusions: A higher HIRI‐MSM cut‐off may be helpful for identifying candidates for PrEP scale‐up. Improving engagement in the PrEP cascade will require interventions to simultaneously address multiple barriers. [ABSTRACT FROM AUTHOR]

Background: Neutrophils play important roles in the homeostasis of periodontal tissues. However, remarkably little is known about how these cells live and die in the gingival crevice and periodontal pocket. We have examined whether subgingival neutrophils die by necrosis or apoptosis and have begun to study the mechanisms controlling the functional lifespan of these cells.Methods: Neutrophils collected from clinically healthy gingival crevices, periodontal pockets, and the oral cavity (saliva) were examined with Hoechst dye 33342, propidium iodide/eithidium bromide, and FITC-annexin V to identify live, dead, and apoptotic cells. Blood neutrophils were cultured for 17 to 20 hours in the presence or absence of gingival crevice washings (GC-w) to study the effect of GC-w on neutrophil apoptosis. In addition, endotoxin was removed from GC-w by affinity resin to investigate the contribution of LPS to the inhibitory effect of GC-w on blood neutrophils.Results: The percentage of dead neutrophils in all subgingival sites and in all oral samples far exceeded the percentage of apoptotic neutrophils. In all 3 locations, approximately 30% of neutrophils were dead, whereas less than 1% of neutrophils were apoptotic. We conclude that the majority of neutrophils which lose their viability within gingival crevices, periodontal pockets and the oral cavity die by necrosis and not by apoptosis. Washings obtained from clinically healthy gingival crevices (GC-w) variably, but significantly, delayed apoptosis of peripheral blood neutrophils (mean suppression 45.7% +/- SD 22.3). Removal of endotoxin from GC-w significantly reduced this inhibitory effect.Conclusions: Our findings provide insights into the mechanisms of neutrophil death and the control of the functional lifespan of neutrophils in gingival crevices and periodontal pockets and therefore into the pathogenesis of periodontal diseases. [ABSTRACT FROM AUTHOR]