Introduction Single-tablet combination emtricitabine/tenofovir is highly effective as HIV pre-exposure prophylaxis (PrEP). Scale-up efforts have targeted men who have sex with men (MSM), but patterns of racial disparities in PrEP use have begun to emerge. African, Caribbean and Black (ACB) communities in Canada and USA are also disproportionately affected by HIV, and there is lack of guidance regarding PrEP implementation in this priority population. Methods ACB men from Toronto, Canada were recruited in community settings by peers. Participants completed a detailed socio-behavioural questionnaire. Biological samples were collected and tested for sexually transmitted infections. Willingness to accept PrEP was assessed in relation to actual and self-perceived risk of acquiring HIV, as well as demographic and behavioural variables. Results 424 ACB men were included in the analysis. ACB MSM were more likely to accept PrEP than ACB men only reporting sex with women (MSW; 50.0% vs. 23.6%). The most common reasons for PrEP non-acceptance were concerns regarding side-effects and low self-perceived risk. PrEP acceptance was lowest among younger men (12.5%) and those born in Canada (15.2%). Men with a high self-perceived HIV risk were more likely to accept PrEP (41.3% vs. 22.7% of men with a low self-perceived risk), but only 25.4% of men who were defined as being at high-risk, self-identified themselves as such. Conclusions Most ACB MSW were unlikely to accept PrEP, largely due to low self-perceived HIV risk, but PrEP acceptance among ACB MSM was similar to other contemporaneous Toronto MSM communities. PrEP acceptance was particularly low among younger ACB men and those born in Canada. Tailored strategies will be needed to effectively implement PrEP in Toronto ACB communities.

Objectives To determine the time to CD4 : CD8 ratio normalization among Canadian adults living with HIV in the modern ART era. To identify characteristics associated with ratio normalization. Patients and methods Retrospective analysis of the Canadian Observational Cohort (CANOC), an interprovincial cohort of ART-naive adults living with HIV, recruited from 11 treatment centres across Canada. We studied participants initiating ART between 1 January 2011 and 31 December 2016 with baseline CD4 : CD8 ratio <1.0 and ≥2 follow-up measurements. Normalization was defined as two consecutive CD4 : CD8 ratios ≥1.0. Kaplan–Meier estimates and log-rank tests described time to normalization. Univariable and multivariable proportional hazards (PH) models identified factors associated with ratio normalization. Results Among 3218 participants, 909 (28%) normalized during a median 2.6 years of follow-up. Participants with higher baseline CD4+ T-cell count were more likely to achieve normalization; the probability of normalization by 5 years was 0.68 (95% CI 0.62–0.74) for those with baseline CD4+ T-cell count >500 cells/mm3 compared with 0.16 (95% CI 0.11–0.21) for those with ≤200 cells/mm3 (P < 0.0001). In a multivariable PH model, baseline CD4+ T-cell count was associated with a higher likelihood of achieving ratio normalization (adjusted HR = 1.5, 95% CI 1.5–1.6 per 100 cells/mm3, P < 0.0001). After adjusting for baseline characteristics, time-dependent ART class was not associated with ratio normalization. Conclusions Early ART initiation, at higher baseline CD4+ T-cell counts, has the greatest impact on CD4 : CD8 ratio normalization. Our study supports current treatment guidelines recommending immediate ART start, with no difference in ratio normalization observed based on ART class used.

RNA toxins are a group of enzymes primarily synthesized by bacteria, fungi, and plants that either cleave or depurinate RNA molecules. These proteins may be divided according to their RNA substrates: ribotoxins are nucleases that cleave ribosomal RNA (rRNA), ribosome inactivating proteins are glycosidases that remove a base from rRNA, messenger RNA (mRNA) interferases are nucleases that cleave mRNAs, and anticodon nucleases cleave transfer RNAs (tRNAs). These modifications to the RNAs may substantially alter gene expression and translation rates. Given that some of these enzymes cause cell death, it has been suggested that they function mainly in defense, either to kill competing cells or to elicit suicide and thereby limit pathogen spread from infected cells. Although good correlations have been drawn between their enzymatic functions and toxicity, recent work has shown that some RNA toxins cause apoptosis in the absence of damage to RNA and that defense against pathogens can be achieved without host cell death. Moreover, a decrease in cellular translation rate, insufficient to cause cell death, allows some organisms to adapt to stress and environmental change. Although ascribing effects observed in vitro to the roles of these toxins in nature has been challenging, recent results have expanded our understanding of their modes of action, and emphasized the importance of these toxins in development, adaptation to stress and defense against pathogens.

Nocardia is found worldwide in soil and decaying plant matter and can cause infection through inhalation of cell fragments in dust particles.

Objectives: The majority of patients with mild-to-moderate COVID-19 can be managed using virtual care. Dyspnea is challenging to assess remotely, and the accuracy of subjective dyspnea measures in capturing hypoxemia have not been formally evaluated for COVID-19. We explored the accuracy of subjective dyspnea in diagnosing hypoxemia in COVID-19 patients. Methods: This is a retrospective cohort study of consecutive outpatients with COVID-19 who met criteria for home oxygen saturation monitoring at a university-affiliated acute care hospital in Toronto, Canada from April 3, 2020 to June 8, 2020. Hypoxemia was defined by oxygen saturation <95%. Dyspnea measures were treated as diagnostic tests, and we determined their sensitivity (SN), specificity (SP), negative/positive predictive value (NPV/PPV), and positive/negative likelihood ratios (+LR/-LR) for detecting hypoxemia. Results: During the study period 64/298 (21.5%) of patients met criteria for home oxygen saturation monitoring, and of these 14/64 (21.9%) were diagnosed with hypoxemia. The presence/absence of dyspnea had limited accuracy for diagnosing hypoxemia, with SN 57% (95% CI 30-81%), SP 78% (63%-88%), NPV 86% (72%-94%), PPV 42% (21%-66%), +LR 2.55 (1.3-5.1), -LR 0.55 (0.3-1.0). An mMRC dyspnea score >1 (SP 97%, 95%CI 82%-100%), Roth Maximal Count <12 (SP 100%, 95%CI 75-100%), and Roth Counting time < 8 seconds (SP 93%, 95%CI 66%-100%) had high SP that could be used to rule in hypoxemia, but displayed low SN (≤50%). Conclusions: Subjective dyspnea measures have inadequate accuracy for ruling out hypoxemia in high-risk patients with COVID-19. Safe home management of patients with COVID-19 should incorporate home oxygenation saturation monitoring.