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INTRODUCTION: Hepatitis B virus (HBV) reactivation (HBVr) induced by chemotherapy in patients with resolved or chronic infection can lead to severe consequences. Despite recommendations, rates of HBV screening before chemotherapy are low due to poor recognition of risk factors by clinicians. The aim of the study is to assess whether routine HBV screening using universal HBV screening on chemotherapy orders (CO) could reduce HBVr incidence. METHODS: This is a 1-year retrospective single-center observational study of patients who received intravenous chemotherapy post implementation of CO. We compared the incidence of HBVr in three groups of patients: those screened through CO (group 1), those screened by the medical team (group 2), and those not screened (group 3). RESULTS: On a total of 1374 patients, 179 of 206 patients were screened as requested on CO (group 1) and 421 by the medical team (group 2), whereas 747 patients were not screened (group 3). Only one HBVr occurred, and no difference was seen on the incidence of HBVr between group 1 and group 3 (0% vs 0.1%; p = 1.00), probably because of a lack of follow-up after chemotherapy. Follow-up for HBVr was imperfect in group 1 and group 2 (16.7% vs 5.6%; p = 0.32). Screening was done for 92% of patients on anti-CD20 therapy. In group 3, 89 patients had ALT elevation during chemotherapy but only 17 (19%) were tested for HBVr. CONCLUSION: Systematic HBV detection requested on CO is an effective way to obtain a high percentage of patients with adequate screening, particularly when chemotherapy is at high risk of HBVr. Nevertheless, this screening method do not guarantee optimal follow-up and requires improvements.
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Antineoplásicos , Virus de la Hepatitis B , Hepatitis B , Neoplasias , Activación Viral , Humanos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Activación Viral/efectos de los fármacos , Hepatitis B/epidemiología , Hepatitis B/diagnóstico , Virus de la Hepatitis B/aislamiento & purificación , Virus de la Hepatitis B/efectos de los fármacos , Anciano , Neoplasias/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Incidencia , Tamizaje Masivo/métodos , Adulto , Factores de RiesgoRESUMEN
Background: The cascade of care, commonly used to assess HIV and hepatitis C (HCV) health service delivery, has limitations in capturing the complexity of individuals' engagement patterns. This study examines the dynamic nature of engagement and mortality trajectories among people with HIV and HCV. Methods: We used data from the Canadian HIV-HCV Co-Infection Cohort, which prospectively follows 2098 participants from 18 centers biannually. Markov multistate models were used to evaluate sociodemographic and clinical factors associated with transitioning between the following states: (1) lost-to-follow-up (LTFU), defined as no visit for 18 months; (2) reengaged (reentry into cohort after being LTFU); (3) withdrawn from the study (ie, moved); (4) death; otherwise remained (5) engaged-in-care. Results: A total of 1809 participants met the eligibility criteria and contributed 12 591 person-years from 2003 to 2022. LTFU was common, with 46% experiencing at least 1 episode, of whom only 57% reengaged. One in 5 (n = 383) participants died during the study. Participants who transitioned to LTFU were twice as likely to die as those who were consistently engaged. Factors associated with transitioning to LTFU included detectable HCV RNA (adjusted hazards ratio [aHR], 1.37; 95% confidence interval [CI], 1.13-1.67), evidence of HCV treatment but no sustained virologic response result (aHR, 1.99; 95% CI, 1.56-2.53), and recent incarceration (aHR, 1.94; 95% CI, 1.58-2.40). Being Indigenous was a significant predictor of death across all engagement trajectories. Interpretation: Disengagement from clinical care was common and resulted in higher death rates. People LTFU were more likely to require HCV treatment highlighting a priority population for elimination strategies.
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INTRODUCTION: Limited data exists on psychological impacts of the COVID-19 pandemic among people who use drugs (PWUD). This study aimed to determine the prevalence and correlates of severe psychological distress (PD) among PWUD in Montreal around the beginning of the pandemic. METHODS: We conducted a rapid assessment study from May to December 2020 among PWUD recruited via a community-based cohort of people who inject drugs in Montreal (Hepatitis C cohort [HEPCO], N = 128) and community organisations (N = 98). We analysed self-reported data on changes in drug use behaviours and social determinants since the declaration of COVID-19 as a public health emergency, and assessed past-month PD using the Kessler K6 scale. Multivariable logistic regression was conducted to examine correlates of PD distress (score ≥13). RESULTS: Of 226 survey participants, a quarter (n = 56) were screened positive for severe PD. In multivariable analyses, age (1-year increment) (adjusted odds ratio = 0.94, 95% confidence interval [0.90, 0.98]) and a decrease in non-injection drug use versus no change (0.26 [0.07, 0.92]) were protective against severe PD, while positive associations were found for any alcohol use in the past 6 months (3.73 [1.42, 9.78]), increased food insecurity (2.88 [1.19, 6.93]) and both moving around between neighbourhoods more (8.71 [2.63, 28.88]) and less (3.03 [1.18, 7.74]) often compared to no change. DISCUSSION AND CONCLUSIONS: This study documented a high prevalence of severe PD among PWUD during the COVID-19 pandemic compared with pre-COVID-19 data. Social determinants such as food insecurity and mobility issues, alongside demographic and substance use-related factors, were linked to distress. Evidence-based risk mitigation strategies for this population could reduce negative consequences in future pandemics or disruptions.
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Interleukin 32 (IL-32) is a potent multi-isoform proinflammatory cytokine, which is upregulated in people with HIV (PWH) and is associated with cardiovascular disease (CVD) risk. However, the impact of IL-32 isoforms on CD4 T-cell cardiotropism, a mechanism potentially contributing to heart inflammation, remains unknown. Here we show that IL-32 isoforms ß and γ induce the generation of CCR4+CXCR3+ double positive (DP) memory CD4 T-cell subpopulation expressing the tyrosine kinase receptor c-Met, a phenotype associated with heart-homing of T cells. Our ex vivo studies on PWH show that the frequency of DP CD4 T cells is significantly higher in individuals with, compared to individuals without, subclinical atherosclerosis and that DP cells from antiretroviral-naive and treated individuals are highly enriched with HIV DNA. Together, these data demonstrate that IL-32 isoforms have the potential to induce heart-homing of HIV-infected CD4 T cells, which may further aggravate heart inflammation and CVD in PWH.
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Linfocitos T CD4-Positivos , Infecciones por VIH , Interleucinas , Femenino , Humanos , Masculino , Linfocitos T CD4-Positivos/inmunología , Diferenciación Celular , ADN Viral , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1 , Interleucinas/metabolismo , Interleucinas/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismoRESUMEN
While an important part of the world's population is vaccinated against SARS-CoV-2, new variants continue to emerge. We observe that even after a fifth dose of the mRNA bivalent vaccine, most vaccinated individuals have antibodies that poorly neutralize several Omicron subvariants, including BQ.1.1, XBB, XBB.1.5, FD.1.1, and CH.1.1. However, Fc-effector functions remain strong and stable over time against new variants, which may partially explain why vaccines continue to be effective. We also observe that donors who have been recently infected have stronger antibody functional activities, including neutralization and Fc-effector functions, supporting the observations that hybrid immunity leads to better humoral responses.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/prevención & control , Anticuerpos , Vacunas Combinadas , ARN Mensajero/genéticaRESUMEN
BACKGROUND: People Who Use Drugs (PWUD) have lower vaccination uptake than the general population, and disproportionately experience the burden of harms from vaccine-preventable diseases. We conducted a national qualitative study to: (1) identify the barriers and facilitators to receiving COVID-19 vaccinations among PWUD; and (2) identify interventions to support PWUD in their decision-making. METHODS: Between March and October 2022, semi-structured interviews with PWUD across Canada were conducted. Fully vaccinated (2 or more doses) and partially or unvaccinated (1 dose or less) participants were recruited from a convenience sample to participate in telephone interviews to discuss facilitators, barriers, and concerns about receiving COVID-19 vaccines and subsequent boosters, and ways to address concerns. A total of 78 PWUD participated in the study, with 50 participants being fully vaccinated and 28 participants partially or unvaccinated. Using thematic analysis, interviews were coded based on the capability, opportunity, and motivation-behavior (COM-B) framework. RESULTS: Many partially or unvaccinated participants reported lacking knowledge about the COVID-19 vaccine, particularly in terms of its usefulness and benefits. Some participants reported lacking knowledge around potential long-term side effects of the vaccine, and the differences of the various vaccine brands. Distrust toward government and healthcare agencies, the unprecedented rapidity of vaccine development and skepticism of vaccine effectiveness were also noted as barriers. Facilitators for vaccination included a desire to protect oneself or others and compliance with government mandates which required individuals to get vaccinated in order to access services, attend work or travel. To improve vaccination uptake, the most trusted and appropriate avenues for vaccination information sharing were identified by participants to be people with lived and living experience with drug use (PWLLE), harm reduction workers, or healthcare providers working within settings commonly visited by PWUD. CONCLUSION: PWLLE should be supported to design tailored information to reduce barriers and address mistrust. Resources addressing knowledge gaps should be disseminated in areas and through organizations where PWUD frequently access, such as harm reduction services and social media platforms.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , COVID-19/prevención & control , Vacunación , Canadá , GobiernoRESUMEN
Cellular immune defects associated with suboptimal responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination in people receiving hemodialysis (HD) are poorly understood. We longitudinally analyze antibody, B cell, CD4+, and CD8+ T cell vaccine responses in 27 HD patients and 26 low-risk control individuals (CIs). The first two doses elicit weaker B cell and CD8+ T cell responses in HD than in CI, while CD4+ T cell responses are quantitatively similar. In HD, a third dose robustly boosts B cell responses, leads to convergent CD8+ T cell responses, and enhances comparatively more T helper (TH) immunity. Unsupervised clustering of single-cell features reveals phenotypic and functional shifts over time and between cohorts. The third dose attenuates some features of TH cells in HD (tumor necrosis factor alpha [TNFα]/interleukin [IL]-2 skewing), while others (CCR6, CXCR6, programmed cell death protein 1 [PD-1], and HLA-DR overexpression) persist. Therefore, a third vaccine dose is critical to achieving robust multifaceted immunity in hemodialysis patients, although some distinct TH characteristics endure.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , SARS-CoV-2/genética , COVID-19/prevención & control , Linfocitos T CD4-Positivos , Vacunas de ARNmRESUMEN
BACKGROUND: Barriers to HCV treatment initiation persisted after the introduction of direct-acting antivirals (DAAs) in Canada among people who inject drugs (PWID); whether DAA universal coverage lifted these barriers remain unknown. We assessed the evolution of HCV treatment initiation and associated factors among PWID in Montreal, Canada, comparing eras of IFN-based regimens (2011-2013), of DAA restricted access (2014-02/2018), and universal coverage (03/2018-03/2020). METHODS: We included chronically HCV-infected participants followed in a community-based PWID cohort in Montreal, Canada between 2011 and 03/2020 and collected data at 3-month intervals. Time-updated Cox regressions were conducted to examine 9 variables of interest associated with treatment initiation overall and for each of the three eras. RESULTS: Of 276 participants, 126 initiated treatment during follow-up. Yearly initiation increased from 3% in 2011 to 19% in 2016, and 54% in 2018. PWID aged >40 (vs. ≤40) were twice as likely to initiate treatment in 2014-02/2018 (HR: 2.02 95%CI: [1.24-3.28]) but not in other periods (2011-2013: 0.55 [0.25-1.22]; 03/2018-03/2020: 1.14 [0.59-2.22])). Odds of initiation were lower for men than women in all periods, with women three times more likely to be treated under universal coverage (0.30 [0.11-0.77] vs 2011-2013: 0.67 [0.25-1.78] and 2014-02/2018: 0.75 [0.42-1.35]). Recent incarceration was negatively associated with initiation throughout all periods (2011-2013: 0.57 [0.13-2.43]; 2014-03/2018: 0.39 [0.17-0.91]; 03/2018-03/2020: 0.25 [0.07-0.83]). Barriers associated with high injection frequency appear to have diminished since DAA introduction (2014-02/2018: 0.71 [0.42-1.20]; 03/2018-03/2020: 1.05 [0.52-2.11] vs. 2011-2013: 0.26 [0.08-0.88]). Contact with a primary care physician and engagement in opioid agonist therapy were positively associated with treatment initiation, though estimates were attenuated under universal coverage relative to previous eras. CONCLUSION: Treatment initiation rates have increased since the introduction of universal DAA coverage, though barriers such as incarceration persist.
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Hepatitis C Crónica , Abuso de Sustancias por Vía Intravenosa , Masculino , Humanos , Femenino , Antivirales , Abuso de Sustancias por Vía Intravenosa/complicaciones , Cobertura Universal del Seguro de Salud , Hepatitis C Crónica/tratamiento farmacológico , CanadáRESUMEN
The Omicron BQ.1.1 variant is now the major SARS-CoV-2 circulating strain in many countries. Because of the many mutations present in its Spike glycoprotein, this variant is resistant to humoral responses elicited by monovalent mRNA vaccines. With the goal to improve immune responses against Omicron subvariants, bivalent mRNA vaccines have recently been approved in several countries. In this study, we measure the capacity of plasma from vaccinated individuals, before and after a fourth dose of mono- or bivalent mRNA vaccine, to recognize and neutralize the ancestral (D614G) and the BQ.1.1 Spikes. Before and after the fourth dose, we observe a significantly better recognition and neutralization of the ancestral Spike. We also observe that fourth-dose vaccinated individuals who have been recently infected better recognize and neutralize the BQ.1.1 Spike, independently of the mRNA vaccine used, than donors who have never been infected or have an older infection. Our study supports that hybrid immunity, generated by vaccination and a recent infection, induces higher humoral responses than vaccination alone, independently of the mRNA vaccine used.
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Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants have recently emerged, becoming the dominant circulating strains in many countries. These variants contain a large number of mutations in their spike glycoprotein, raising concerns about vaccine efficacy. In this study, we evaluate the ability of plasma from a cohort of individuals that received three doses of mRNA vaccine to recognize and neutralize these Omicron subvariant spikes. We observed that BA.4/5 and BQ.1.1 spikes are markedly less recognized and neutralized compared with the D614G and other Omicron subvariant spikes tested. Also, individuals who have been infected before or after vaccination present better humoral responses than SARS-CoV-2-naive vaccinated individuals, thus indicating that hybrid immunity generates better humoral responses against these subvariants.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/prevención & control , Vacunas Sintéticas , Mutación , Anticuerpos Antivirales , Anticuerpos Neutralizantes , Vacunas de ARNmRESUMEN
Spacing the first two doses of SARS-CoV-2 mRNA vaccines beyond 3-4 weeks raised initial concerns about vaccine efficacy. While studies have since shown that long-interval regimens induce robust antibody responses, their impact on B and T cell immunity is poorly known. Here, we compare SARS-CoV-2 naive donors B and T cell responses to two mRNA vaccine doses administered 3-4 versus 16 weeks apart. After boost, the longer interval results in a higher magnitude and a more mature phenotype of RBD-specific B cells. While the two geographically distinct cohorts present quantitative and qualitative differences in T cell responses at baseline and after priming, the second dose led to convergent features with overall similar magnitude, phenotype, and function of CD4+ and CD8+ T cell responses at post-boost memory time points. Therefore, compared to standard regimens, a 16-week interval has a favorable impact on the B cell compartment but minimally affects T cell immunity.
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BACKGROUND: Direct-acting antiviral agents (DAAs) have transformed chronic hepatitis C (CHC) treatment. Continued affordable access to DAAs requires updated cost-effectiveness analyses (CEA). Utility is a preference-based measure of health-related quality of life (HRQoL) used in CEA. This study evaluated the impact of DAAs on utilities for patients with CHC in two clinical settings. METHODS: This prospective longitudinal study included patients aged ≥18 years, diagnosed with CHC and scheduled to begin DAA treatment, from two tertiary care hospital clinics and four community clinics in Toronto, Calgary, and Montreal. Patients completed two utility instruments (EQ-5D-5L and Health Utilities Index 2/3 (HUI2/3)) before treatment, 6 weeks after treatment initiation, and 12 weeks and 1 year after treatment completion. We measured utilities for all patients, and for hospital-based and community-based groups. RESULTS: Between 2017 and 2020, 209 patients (126 hospital-based, 83 community-based; average age 53 years; 65% male) were recruited, and 143 completed the 1-year post-treatment assessment. Pre-treatment, utilities were (mean ± standard deviation) 0.77 ± 0.21 (EQ-5D-5L), 0.69 ± 0.24 (HUI2) and 0.58 ± 0.34 (HUI3). The mean changes at 1-year post-treatment were 0.035, 0.038 and 0.071, respectively. While utilities for hospital-based patients steadily improved, utilities for the community-based cohort improved between baseline and 12-weeks post-treatment, but decreased thereafter. DISCUSSION: This study suggests that utilities improve after DAA treatment in patients with CHC in a variety of settings. However, community-based patients may face challenges related to comorbid health and social conditions that are not meaningfully addressed by treatment. Our study is essential for valuing health outcomes in CHC-related CEA.
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Antivirales , Hepatitis C Crónica , Humanos , Masculino , Adolescente , Adulto , Persona de Mediana Edad , Femenino , Antivirales/uso terapéutico , Calidad de Vida , Hepatitis C Crónica/tratamiento farmacológico , Estudios Prospectivos , Estudios Longitudinales , Encuestas y Cuestionarios , HospitalesRESUMEN
BACKGROUND: Depression is common in people with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), with biological and psychosocial mechanisms at play. Direct acting antivirals (DAA) result in high rates of sustained virologic response (SVR), with minimal side-effects. We assessed the impact of SVR on presence of depressive symptoms in the HIV-HCV coinfected population in Canada during the second-generation DAA era (2013-2020). METHODS: We used data from the Canadian CoInfection Cohort (CCC), a multicenter prospective cohort of people with a HIV and HCV coinfection, and its associated sub-study on food security. Because depression screening was performed only in the sub-study, we predicted Center for Epidemiologic Studies Depression Scale-10 classes in the CCC using a random forest classifier and corrected for misclassification. We included participants who achieved SVR and fit a segmented modified Poisson model using an interrupted time series design, adjusting for time-varying confounders. RESULTS: We included 470 participants; 58% had predicted depressive symptoms at baseline. The median follow-up was 2.4 years (interquartile range [IQR]: 1.0-4.5.) pre-SVR and 1.4 years (IQR: 0.6-2.5) post-SVR. The pre-SVR trend suggested depressive symptoms changed little over time, with no immediate level change at SVR. However, post-SVR trends showed a reduction of 5% per year (risk ratio: 0.95 (95% confidence interval [CI]: .94-.96)) in the prevalence of depressive symptoms. CONCLUSIONS: In the DAA era, predicted depressive symptoms declined over time following SVR. These improvements reflect possible changes in biological pathways and/or better general health. If such improvements in depression symptoms are durable, this provides an additional reason for treatment and early cure of HCV.
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Coinfección , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Humanos , Hepacivirus , Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Coinfección/epidemiología , Coinfección/complicaciones , Depresión/tratamiento farmacológico , Depresión/epidemiología , Estudios Prospectivos , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Canadá/epidemiología , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Respuesta Virológica Sostenida , VIHRESUMEN
Background: Many people living with HIV struggle to consistently adhere to antiretroviral therapy, fail to achieve long-term virologic control and remain at risk for HIV-related disease progression, development of resistance and may transmit HIV infection to others. Objective: To determine if switching from current multi-tablet (curART) to single-tablet antiretroviral therapy (abacavir/lamivudine/dolutegravir; ABC/3TC/DTG), both combined with individualized adherence support, would improve HIV suppression in non-adherent vulnerable populations. Methods: TriiADD was an investigator-initiated randomized, multicentre, open label study. HIV+ adults with documented non-adherence on curART were randomized in a 1:1 ratio to immediately switch to ABC/3TC/DTG or to continue curART. Both arms received adherence support. The primary outcome was the proportion of participants in each arm with HIV RNA < 50 copies/mL 24 weeks after randomization. Results: In total, 50 people were screened and 27 randomized from 11 sites across Canada before the trial was stopped early due to slow recruitment. Participants were predominantly from ethnocultural communities, Indigenous people and/or had a history of injection drug use. The proportion achieving HIV RNA < 50 copies/mL at week 24 was 4/12 (33%) in the curART arm vs 7/13 (54%) in the ABC/3TC/DTG arm; median Bayesian risk difference, 5% (95% CrI, -17 to 28%) higher for those randomized to ABC/3TC/DTG. We encountered difficulties with recruitment of participants without prior drug resistance, retention despite intensive support, reliably measuring adherence and in overcoming entrenched adherence barriers. Conclusion: Results of our trial are consistent with a slight improvement in viral suppression in a vulnerable population when a single tablet regimen is combined with patient-level adherence support. Beyond treatment simplicity and tolerability, tailored interventions addressing stigma and social determinants of health are still needed. The numerous challenges we encountered illustrate how randomised trials may not be the best approach for assessing adherence interventions in vulnerable populations.
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Due to the recrudescence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections worldwide, mainly caused by the Omicron variant of concern (VOC) and its sub-lineages, several jurisdictions are administering an mRNA vaccine boost. Here, we analyze humoral responses induced after the second and third doses of an mRNA vaccine in naive and previously infected donors who received their second dose with an extended 16-week interval. We observe that the extended interval elicits robust humoral responses against VOCs, but this response is significantly diminished 4 months after the second dose. Administering a boost to these individuals brings back the humoral responses to the same levels obtained after the extended second dose. Interestingly, we observe that administering a boost to individuals that initially received a short 3- to 4-week regimen elicits humoral responses similar to those observed in the long interval regimen. Nevertheless, humoral responses elicited by the boost in naive individuals do not reach those present in previously infected vaccinated individuals.
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COVID-19 , Vacunas Virales , Humanos , SARS-CoV-2 , Vacuna BNT162 , COVID-19/prevención & control , Anticuerpos Antivirales , Vacunas contra la COVID-19 , Vacunación , Vacunas de ARNmRESUMEN
This study investigates the impact of the age at which HIV was acquired on adherence. There was no difference in adherence between patients who acquired HIV in childhood vs. those who acquired it in adolescence/early adulthood (83% vs. 90%; p = 0.24), but achievement of virological/immunological efficacy (78.8% vs. 93.5%, p = 0.02) was less likely in patients who had acquired HIV in childhood. On the basis of resistance, patients who acquired HIV in adolescence/early adulthood tended to be more eligible for cabotegravir/rilpivirine treatment (90.3% vs. 80.3%; p = 0.11).
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Background: Historically, hepatitis C virus (HCV) pretreatment evaluation has required multiple visits, frequently resulting in loss to follow-up and a delayed initiation of treatment. New technologies can accelerate this process. We investigated the feasibility of a single-day evaluation program and its impact on evaluation completion, treatment eligibility awareness, and treatment initiation among people who inject drugs (PWIDs). Methods: HCV-infected PWID who were unaware if they were eligible for treatment were recruited in a prospective evaluation of an accelerated model of care between 2017 and 2019 and compared to a historical cohort. The patients underwent a medical evaluation, rapid HCV viral load testing, and transient elastography during a single visit, at the end of which they were informed whether they were eligible for treatment. A historical cohort of patients fulfilling the same inclusion criteria and evaluated with the usual standard of care spanning several visits who were examined at the addiction medicine clinic from 2014 to 2016 served as the comparison group. Results: The accelerated and historical cohorts included 99 and 76 patients, respectively. The cohorts did not differ significantly by age and gender, but more patients in the historical cohort were undergoing opioid agonist therapy, while more patients in the accelerated cohort injected drugs in the last month. An accelerated evaluation resulted in a higher rate of evaluation completion (100% vs 67.1%; P < .001). Among those eligible for treatment, the proportion of those initiating treatment was similar between the groups (51/64 (79.7%) vs. 26/37 (70.3%); P = .28). The delay in the initiation of treatment was shorter in the accelerated cohort than in the historical cohort (69 (IQR: 49-106) days vs. 219 (IQR: 141-416) days; P < .001). Conclusions: Accelerated evaluation enhanced the awareness of eligibility and reduced the time to initiation among eligible patients. Trial Registration: This study is registered on www.clinicaltrials.gov (NCT02755402).
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Although SARS-CoV-2 mRNA vaccination has been shown to be safe and effective in the general population, immunocompromised solid organ transplant recipients (SOTRs) were reported to have impaired immune responses after one or two doses of vaccine. In this study, we examined humoral responses induced after the second and the third dose of mRNA vaccine in different SOTR (kidney, liver, lung, and heart). Compared to a cohort of SARS-CoV-2 naïve immunocompetent health care workers (HCWs), the second dose induced weak humoral responses in SOTRs, except for the liver recipients. The third dose boosted these responses but they did not reach the same level as in HCW. Interestingly, although the neutralizing activity against Delta and Omicron variants remained very low after the third dose, Fc-mediated effector functions in SOTR reached similar levels as in the HCW cohort. Whether these responses will suffice to protect SOTR from severe outcome remains to be determined.
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BACKGROUND: Depression is common in the human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected population. Demographic, behavioural, and clinical data collected in research settings may be of help in identifying those at risk for clinical depression. We aimed to predict the presence of depressive symptoms indicative of a risk of depression and identify important classification predictors using supervised machine learning. METHODS: We used data from the Canadian Co-infection Cohort, a multicentre prospective cohort, and its associated sub-study on Food Security (FS). The Center for Epidemiologic Studies Depression Scale-10 (CES-D-10) was administered in the FS sub-study; participants were classified as being at risk for clinical depression if scores ≥ 10. We developed two random forest algorithms using the training data (80%) and tenfold cross validation to predict the CES-D-10 classes-1. Full algorithm with all candidate predictors (137 predictors) and 2. Reduced algorithm using a subset of predictors based on expert opinion (46 predictors). We evaluated the algorithm performances in the testing data using area under the receiver operating characteristic curves (AUC) and generated predictor importance plots. RESULTS: We included 1,934 FS sub-study visits from 717 participants who were predominantly male (73%), white (76%), unemployed (73%), and high school educated (52%). At the first visit, median age was 49 years (IQR:43-54) and 53% reported presence of depressive symptoms with CES-D-10 scores ≥ 10. The full algorithm had an AUC of 0.82 (95% CI:0.78-0.86) and the reduced algorithm of 0.76 (95% CI:0.71-0.81). Employment, HIV clinical stage, revenue source, body mass index, and education were the five most important predictors. CONCLUSION: We developed a prediction algorithm that could be instrumental in identifying individuals at risk for depression in the HIV-HCV co-infected population in research settings. Development of such machine learning algorithms using research data with rich predictor information can be useful for retrospective analyses of unanswered questions regarding impact of depressive symptoms on clinical and patient-centred outcomes among vulnerable populations.