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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. 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. 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. 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. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email:


Alice Zhabokritsky, Leah Szadkowski, Curtis Cooper, Mona Loutfy, Alexander Wong, Alison McClean, Robert S Hogg, Sharon L Walmsley, Canadian Observational Cohort (CANOC) Collaboration. Increased CD4 : CD8 ratio normalization with implementation of current ART management guidelines. The Journal of antimicrobial chemotherapy. 2021 Feb 11;76(3):729-737

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PMID: 33249444

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