Increased CD4 : CD8 ratio normalization with implementation of current ART management guidelines
Authors: Zhabokritsky Alice , Szadkowski Leah , Cooper Curtis , Loutfy Mona , Wong Alexander , McClean Alison , Hogg Robert S , Walmsley Sharon L ,   the Canadian Observational Cohort (CANOC) Collaboration, Hogg Robert , Brumme Zabrina , Burchell Ann N , Cooper Curtis , Kelly Deborah , Klein Marina , Kroch Abigail , Loutfy Mona , Machouf Nimâ , Montaner Julio , Salters Kate , Raboud Janet , Tsoukas Chris , Sanche Stephen , Thomas Réjean , Walmsley Sharon , Wong Alexander , Antoniou Tony , Bayoumi Ahmed , Hull Mark , Nosyk Bohdan , Cescon Angela , Cotterchio Michelle , Goldsmith Charlie , Guillemi Silvia , Harrigan P Richard , Harris Marianne , Hosein Sean , Johnston Sharon , Kendall Claire , Liddy Clare , Lima Viviane , Moore David , Palmer Alexis , Patterson Sophie , Phillips Peter , Rachlis Anita , Rourke Sean B , Samji Hasina , Smieja Marek , Trottier Benoit , Wainberg Mark , Archibald Chris , Clement Ken , Doolittle-Romas Monique , Edmiston Laurie , Gardner Sandra , Huskins Brian , Lawless Jerry , Lee Douglas , Masching Renee , Tattle Stephen , Zahirieh Alireza , Allen Claire , Calvez Stryker , Colley Guillaume , Chia Jason , Corsi Daniel , Gilbert Louise , Gataric Nada , Light Lucia , Mackie David , Pexos Costa , Shurgold Susan , Szadkowski Leah , Galanakis Chrissi , Yip Benita , Younger Jaime , Zhu Julia 
Published: November 2020

Abstract

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 &lt;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 &gt;500 cells/mm3 compared with 0.16 (95% CI 0.11–0.21) for those with ≤200 cells/mm3 (P &lt; 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 &lt; 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.