Integrated immunovirological profiling validates plasma SARS-CoV-2 RNA as an early predictor of COVID-19 mortality.

peer reviewedDespite advances in COVID-19 management, identifying patients evolving toward death remains challenging. To identify early predictors of mortality within 60 days of symptom onset (DSO), we performed immunovirological assessments on plasma from 279 individuals. On samples collected at DSO11 in a discovery cohort, high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA (vRNA), low receptor binding domain–specific immunoglobulin G and antibody-dependent cellular cytotoxicity, and elevated cytokines and tissue injury markers were strongly associated with mortality, including in patients on mechanical ventilation. A three-variable model of vRNA, with predefined adjustment by age and sex, robustly identified patients with fatal outcome (adjusted hazard ratio for log-transformed vRNA = 3.5). This model remained robust in independent validation and confirmation cohorts. Since plasma vRNA’s predictive accuracy was maintained at earlier time points, its quantitation can help us understand disease heterogeneity and identify patients who may benefit from new therapies

The Frequency and Function of NKG2C+CD57+ Adaptive NK Cells in Cytomagalovirus Co-Infected People Living with HIV Decline with Duration of Antiretroviral Therapy

Human cytomegalovirus (CMV) infection drives the expansion and differentiation of natural killer (NK) cells with adaptive-like features. We investigated whether age and time on antiretroviral therapy (ART) influenced adaptive NK cell frequency and functionality. Flow cytometry was used to evaluate the frequency of adaptive and conventional NK cells in 229 CMV+ individuals of whom 170 were people living with HIV (PLWH). The frequency of these NK cell populations producing CD107a, CCL4, IFN-γ or TNF-α was determined following a 6-h antibody dependent (AD) stimulation. Though ART duration and age were correlated, longer time on ART was associated with a reduced frequency of adaptive NK cells. In general, the frequency and functionality of NK cells following AD stimulation did not differ significantly between treated CMV+PLWH and CMV+HIV- persons, suggesting that HIV infection, per se, did not compromise AD NK cell function. AD activation of adaptive NK cells from CMV+PLWH induced lower frequencies of IFN-γ or TNF-α secreting cells in older persons, when compared with younger persons

The Frequency and Function of NKG2C⁺CD57⁺ Adaptive NK Cells in Cytomagalovirus Co-Infected People Living with HIV Decline with Duration of Antiretroviral Therapy

Human cytomegalovirus (CMV) infection drives the expansion and differentiation of natural killer (NK) cells with adaptive-like features. We investigated whether age and time on antiretroviral therapy (ART) influenced adaptive NK cell frequency and functionality. Flow cytometry was used to evaluate the frequency of adaptive and conventional NK cells in 229 CMV+ individuals of whom 170 were people living with HIV (PLWH). The frequency of these NK cell populations producing CD107a, CCL4, IFN-γ or TNF-α was determined following a 6-h antibody dependent (AD) stimulation. Though ART duration and age were correlated, longer time on ART was associated with a reduced frequency of adaptive NK cells. In general, the frequency and functionality of NK cells following AD stimulation did not differ significantly between treated CMV+PLWH and CMV+HIV- persons, suggesting that HIV infection, per se, did not compromise AD NK cell function. AD activation of adaptive NK cells from CMV+PLWH induced lower frequencies of IFN-γ or TNF-α secreting cells in older persons, when compared with younger persons

Population-level sexual mixing by HIV status and pre-exposure prophylaxis use among men who have sex with men in Montreal, Canada: implications for HIV prevention

There is are limited data on population-level mixing patterns by HIV status or pre- exposure prophylaxis (PrEP) use. Using cross-sectional survey data (Engage, 2017- 2018) of 1137 men who have sex with men (MSM) ≥16 year-old in Montreal, we compared observed seroconcordance in the past-six6-month sexual partnerships to what would have been observed by chance if zero individuals serosort. Of five 5 recent partnerships where both individuals were HIV-negative, we compared observed concordance in PrEP use to the counterfactual if zero individuals selected partners based on PrEP use. We estimated the concordance by chance using a balancing- partnerships approach assuming proportionate-mixing. HIV-positive respondents had a higher proportion of HIV-positive partners (66.4% (95% confidence interval: 64.0%- 68.6%)) than by chance (23.9%(23.1%-24.7%)). HIV-negative respondents (both on and not on PrEP) had higher proportions of HIV-negative partners (82.9%(81.1%- 84.7%), and 90.7%(89.6%-91.7%), respectively) compared with by chance (82.9%(81.1%-84.7%), and 90.7%(89.6%-91.7%), respectively, vs. 76.1%(75.3%- 76.9%)); but those on PrEP had a higher proportion of HIV-positive partners than those not on PrEP (17.1%(15.3%-18.9%) vs. 9.3%(8.3%-10.4%)). Those on PrEP also had a higher proportion of partners on PrEP among their HIV-negative partners (50.6%(42.5%-58.8%)) than by chance (28.5%(27.5%-29.4%)). The influence ofrelationship between PrEP on and sexual-mixing patterns demonstrated by less population-level serosorting among those on PrEP and PrEP-matching warrants consideration during PrEP roll-out.<br/

HIV pre-exposure prophylaxis (PrEP) use among Urban Canadian gay, bisexual and other men who have sex with men for whom PrEP is clinically recommended: baseline results from the Engage cohort study

Background: in Canada, gay, bisexual and other men who have sex with men (GBM) are disproportionately affected by HIV. Use of HIV pre-exposure prophylaxis (PrEP) by GBM for whom PrEP is clinically recommended, is unknown. We report on PrEP access and factors associated with not using PrEP, among HIV-negative/unknown GBM in Montreal, Toronto and Vancouver. Methods: from 2017 to 2019, the Engage study recruited sexually-active GBM≥16 years in Montréal(M), Toronto(T), and Vancouver(V) via respondent-driven sampling (RDS). Participation included HIV/STI testing and a questionnaire. We examined PrEP access using a health services model and fit RDS-adjusted logistic regressions to determine correlates of not using PrEP among those who were PrEP-aware and clinically recommended. Results: a total of 2449 GBM were recruited. 2008 were HIV-negative/unknown with 1159 (n=511(M), n=247(T), n=401(V)) meeting PrEP recommendations. Of these, 1100 were PrEP-aware (RDS-adjusted %: M=85%, T=94%, V=93%), 678 felt the need for PrEP (M=39%, T=56%, V=49%), 406 tried to access it (M=21%, T=33%, V=30%) and 319 used PrEP (M=15%, T=22%, V=22%) in the past 6 months. Not using PrEP was associated with several factors, including not feeling at high enough risk, viewing PrEP as not completely effective, not having a primary care provider, and lacking medication insurance. Conclusion: while half of GBM from Canada’s three largest cities met clinical recommendations for PrEP, less than a quarter reported use. Despite high levels of awareness, a programmatic response that addresses PrEP-related perceptions and health system barriers is needed to scale-up PrEP access and ultimately end the HIV epidemic among GBM in Canada.<br/