COVID-19 vaccine effectiveness against symptomatic infection with SARS-CoV-2 BA.1/BA.2 lineages among adults and adolescents in a multicentre primary care study, Europe, December 2021 to June 2022.

BackgroundScarce European data in early 2021 suggested lower vaccine effectiveness (VE) against SARS-CoV-2 Omicron lineages than previous variants.AimWe aimed to estimate primary series (PS) and first booster VE against symptomatic BA.1/BA.2 infection and investigate potential biases.MethodsThis European test-negative multicentre study tested primary care patients with acute respiratory symptoms for SARS-CoV-2 in the BA.1/BA.2-dominant period. We estimated PS and booster VE among adults and adolescents (PS only) for all products combined and for Comirnaty alone, by time since vaccination, age and chronic condition. We investigated potential bias due to correlation between COVID-19 and influenza vaccination and explored effect modification and confounding by prior SARS-CoV-2 infection.ResultsAmong adults, PS VE was 37% (95% CI: 24-47%) overall and 60% (95% CI: 44-72%), 43% (95% CI: 26-55%) and 29% (95% CI: 13-43%) < 90, 90-179 and ≥ 180 days post vaccination, respectively. Booster VE was 42% (95% CI: 32-51%) overall and 56% (95% CI: 47-64%), 22% (95% CI: 2-38%) and 3% (95% CI: -78% to 48%), respectively. Primary series VE was similar among adolescents. Restricting analyses to Comirnaty had little impact. Vaccine effectiveness was higher among older adults. There was no signal of bias due to correlation between COVID-19 and influenza vaccination. Confounding by previous infection was low, but sample size precluded definite assessment of effect modification.ConclusionPrimary series and booster VE against symptomatic infection with BA.1/BA.2 ranged from 37% to 42%, with similar waning post vaccination. Comprehensive data on previous SARS-CoV-2 infection would help disentangle vaccine- and infection-induced immunity.

Public health interventions, priority populations, and the impact of COVID-19 disruptions on hepatitis C elimination among people who have injected drugs in Montreal (Canada): A modeling study.

BACKGROUND: In Montreal (Canada), high hepatitis C virus (HCV) seroincidence (21 per 100 person-years in 2017) persists among people who have injected drugs (PWID) despite relatively high testing rates and coverage of needle and syringe programs (NSP) and opioid agonist therapy (OAT). We assessed the potential of interventions to achieve HCV elimination (80% incidence reduction and 65% reduction in HCV-related mortality between 2015 and 2030) in the context of COVID-19 disruptions among all PWID and PWID living with HIV. METHODS: Using a dynamic model of HCV-HIV co-transmission, we simulated increases in NSP (from 82% to 95%) and OAT (from 33% to 40%) coverage, HCV testing (every 6 months), or treatment rate (100 per 100 person-years) starting in 2022 among all PWID and PWID living with HIV. We also modeled treatment scale-up among active PWID only (i.e., people who report injecting in the past six months). We reduced intervention levels in 2020-2021 due to COVID-19-related disruptions. Outcomes included HCV incidence, prevalence, and mortality, and proportions of averted chronic HCV infections and deaths. RESULTS: COVID-19-related disruptions could have caused temporary rebounds in HCV transmission. Further increasing NSP/OAT or HCV testing had little impact on incidence. Scaling-up treatment among all PWID achieved incidence and mortality targets among all PWID and PWID living with HIV. Focusing treatment on active PWID could achieve elimination, yet fewer projected deaths were averted (36% versus 48%). CONCLUSIONS: HCV treatment scale-up among all PWID will be required to eliminate HCV in high-incidence and prevalence settings. Achieving elimination by 2030 will entail concerted efforts to restore and enhance pre-pandemic levels of HCV prevention and care.

The rate of hepatitis C reinfection in Canadians coinfected with HIV and its implications for national elimination.

BACKGROUND: The World Health Organisation (WHO) has set targets for the rate of new infections as a way to measure progress towards the elimination of hepatitis C virus (HCV) as a public health threat. As more people are successfully treated for HCV, a higher proportion of new infections will be reinfections. We consider whether the reinfection rate has changed since the interferon era and what we can infer about national elimination efforts from the current reinfection rate. METHODS: The Canadian Coinfection Cohort is representative of HIV HCV coinfected people in clinical care. We selected cohort participants successfully treated for a primary HCV infection either in the interferon era or in the era of direct acting antivirals (DAAs). Selected participants were followed from 12 weeks after completing a successful treatment until the end of 2019 or until their last measured HCV RNA. We estimated the reinfection rate in each treatment era, overall and in participant subgroups, using proportional hazard models appropriate for interval censored data. RESULTS: Among 814 successfully treated participants with additional HCV RNA measurements, there were 62 reinfections. The overall reinfection rate was 2.6 (95% confidence interval, CI, 1.2-4.1) /100 person years (PY) in the interferon era and 3.4 (95% CI 2.5-4.4) /100 PY in the DAA era. The rate in those reporting injection drug use (IDU) was much higher: 4.7 (95% CI 1.4-7.9) /100 PY and 7.6 (95% CI 5.3-10) /100 PY in the interferon and DAA eras respectively. CONCLUSION: The overall reinfection rate in our cohort is now above the WHO target set for new infections in people who inject drugs. The reinfection rate in those reporting IDU has increased since the interferon era. This suggests Canada is not on track to achieve HCV elimination by 2030.

Impact of Hepatitis C Virus Cure on Depressive Symptoms in the Human Immunodeficiency Virus-Hepatitis C Virus Coinfected Population in Canada.

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.

Gaps in hepatitis C virus prevention and care for HIV-hepatitis C virus co-infected people who inject drugs in Canada.

BACKGROUND: People who inject drugs (PWID) living with HIV are a priority population for eliminating hepatitis C virus (HCV) as a public health threat. Maximizing access to HCV prevention and treatment strategies are key steps towards elimination. We aimed to evaluate engagement in harm reduction programs and HCV treatment, and to describe injection practices among HIV-HCV co-infected PWID in Canada from 2003 to 2019. METHODS: We included Canadian Coinfection Cohort study participants who reported injecting drugs between 2003 and 2019 in Quebec, Ontario, Saskatchewan, and British Columbia, Canada. We investigated temporal trends in HCV treatment uptake, efficacy, and effectiveness; injection practices; and engagement in harm reduction programs in three time periods based on HCV treatment availability: 1) interferon/ribavirin (2003-2010); 2) first-generation direct acting antivirals (DAAs) (2011-2013); 3) second-generation DAAs (2014-2019). Harm reduction services assessed included needle and syringe programs (NSP), opioid agonist therapy (OAT), and supervised injection sites (SIS). RESULTS: Median age of participants (N = 1,077) at cohort entry was 44 years; 69% were males. Province-specific HCV treatment rates increased among HCV RNA-positive PWID, reaching 16 to 31 per 100 person-years in 2014-2019. Treatment efficacy improved from a 50 to 70% range in 2003-2010 to >90% across provinces in 2014-2019. Drug injecting patterns among active PWID varied by province, with an overall decrease in cocaine injection frequency and increasing opioid injections. In the most recent time period (2014-2019), needle/syringe sharing was reported at 8-22% of visits. Gaps remained in engagement in harm reduction programs: NSP use decreased (58-70% of visits), OAT engagement among opioid users was low (8-26% of visits), and participants rarely used SIS (1-15% of visits). CONCLUSION: HCV treatment uptake and outcomes have improved among HIV-HCV coinfected PWID. Yet, this population remains exposed to drug-related harms, highlighting the need to tie HCV elimination strategies with enhanced harm reduction programs to improve overall health for this population.

Can hepatitis C elimination targets be sustained among people who inject drugs post-2030?

BACKGROUND: In high-income countries, people who inject drugs (PWID) are a priority population for eliminating hepatitis C virus (HCV) by 2030. Despite evidence informing micro-elimination strategies, little is known regarding efforts needed to maintain elimination targets in populations with ongoing acquisition risks. This model-based study investigates post-elimination transmission dynamics of HCV and HIV among PWID under different scenarios where harm reduction interventions and HCV testing and treatment are scaled-down. METHODS: We calibrated a dynamic compartmental model of concurrent HCV and HIV transmission among PWID in Montréal (Canada) to epidemiological data (2003-2018). We then simulated achieving the World Health Organization elimination targets by 2030. Finally, we assessed the impact of four post-elimination scenarios (2030-2050): 1) scaling-down testing, treatment, opioid agonist therapy (OAT), and needle and syringe programs (NSP) to pre-2020 levels; 2) only scaling-down testing and treatment; 3) suspending testing and treatment, while scaling down OAT and NSP to pre-2020 levels; 4) suspending testing and treatment and maintaining OAT and NSP coverage required for elimination. RESULTS: Scaling down interventions to pre-2020 levels (scenario 1) leads to a modest rebound in chronic HCV incidence from 2.4 to 3.6 per 100 person-years by 2050 (95% credible interval - CrI: 0.8-7.2). When only scaling down testing and treatment (scenario 2), chronic HCV incidence continues to decrease. In scenario 3 (suspending treatment and scaling down OAT and NSP), HCV incidence and mortality rapidly increase to 11.4 per 100 person-years (95%CrI: 7.4-15.5) and 3.2 per 1000 person-years (95%CrI: 2.4-4.0), respectively. HCV resurgence was mitigated in scenario 4 (maintaining OAT and NSP) as compared to scenario 3. All scenarios lead to decreases in the proportion of reinfections among incident cases and have little impact on HIV incidence and HIV-HCV coinfection prevalence. CONCLUSION: Despite ongoing transmission risks, HCV incidence rebounds slowly after 2030 under pre-2020 testing and treatment levels. This is heightened by maintaining high-coverage harm reduction interventions. Overall, sustaining elimination would require considerably less effort than achieving it.

Trends in hepatitis C virus seroprevalence and associated risk factors among men who have sex with men in Montréal: results from three cross-sectional studies (2005, 2009, 2018).

OBJECTIVES: To eliminate the hepatitis C virus (HCV) by 2030, Canada must adopt a microelimination approach targeting priority populations, including gay, bisexual and other men who have sex with men (MSM). Accurately describing HCV prevalence and risk factors locally is essential to design appropriate prevention and treatment interventions. We aimed to estimate temporal trends in HCV seroprevalence between 2005 and 2018 among Montréal MSM, and to identify socioeconomic, behavioural and biological factors associated with HCV exposure among this population. METHODS: We used data from three cross-sectional surveys conducted among Montréal MSM in 2005 (n=1795), 2009 (n=1258) and 2018 (n=1086). To ensure comparability of seroprevalence estimates across time, we standardised the 2005 and 2009 time-location samples to the 2018 respondent-driven sample. Time trends overall and stratified by HIV status, history of injection drug use (IDU) and age were examined. Modified Poisson regression analyses with generalised estimating equations were used to identify factors associated with HCV seropositivity pooling all surveys. RESULTS: Standardised HCV seroprevalence among all MSM remained stable from 7% (95% CI 3% to 10%) in 2005, to 8% (95% CI 1% to 9%) in 2009 and 8% (95% CI 4% to 11%) in 2018. This apparent stability hides diverging temporal trends in seroprevalence between age groups, with a decrease among MSM <30 years old and an increase among MSM aged ≥45 years old. Lifetime IDU was the strongest predictor of HCV seropositivity, and no association was found between HCV seroprevalence and sexual risk factors studied (condomless anal sex with men of serodiscordant/unknown HIV status, number of sexual partners, group sex). CONCLUSIONS: HCV seroprevalence remained stable among Montréal MSM between 2005 and 2018. Unlike other settings where HCV infection was strongly associated with sexual risk factors among MSM, IDU was the pre-eminent risk factor for HCV seropositivity. Understanding the intersection of IDU contexts, practices and populations is essential to prevent HCV transmission among MSM.

National HIV testing and diagnosis coverage in sub-Saharan Africa: a new modeling tool for estimating the 'first 90' from program and survey data.

OBJECTIVE: HIV testing services (HTS) are a crucial component of national HIV responses. Learning one's HIV diagnosis is the entry point to accessing life-saving antiretroviral treatment and care. Recognizing the critical role of HTS, the Joint United Nations Programme on HIV/AIDS (UNAIDS) launched the 90-90-90 targets stipulating that by 2020, 90% of people living with HIV know their status, 90% of those who know their status receive antiretroviral therapy, and 90% of those on treatment have a suppressed viral load. Countries will need to regularly monitor progress on these three indicators. Estimating the proportion of people living with HIV who know their status (i.e. the 'first 90'), however, is difficult. METHODS: We developed a mathematical model (henceforth referred to as 'Shiny90') that formally synthesizes population-based survey and HTS program data to estimate HIV status awareness over time. The proposed model uses country-specific HIV epidemic parameters from the standard UNAIDS Spectrum model to produce outputs that are consistent with other national HIV estimates. Shiny90 provides estimates of HIV testing history, diagnosis rates, and knowledge of HIV status by age and sex. We validate Shiny90 using both in-sample comparisons and out-of-sample predictions using data from three countries: Côte d'Ivoire, Malawi, and Mozambique. RESULTS: In-sample comparisons suggest that Shiny90 can accurately reproduce longitudinal sex-specific trends in HIV testing. Out-of-sample predictions of the fraction of people living with HIV ever tested over a 4-to-6-year time horizon are also in good agreement with empirical survey estimates. Importantly, out-of-sample predictions of HIV knowledge of status are consistent (i.e. within 4% points) with those of the fully calibrated model in the three countries when HTS program data are included. The model's predictions of knowledge of status are higher than available self-reported HIV awareness estimates, however, suggesting - in line with previous studies - that these self-reports could be affected by nondisclosure of HIV status awareness. CONCLUSION: Knowledge of HIV status is a key indicator to monitor progress, identify bottlenecks, and target HIV responses. Shiny90 can help countries track progress towards their 'first 90' by leveraging surveys of HIV testing behaviors and annual HTS program data.