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Clinical impact of altered T-cell homeostasis in treated HIV patients enrolled in a large observational cohort

Ndumbi, Patriciaa; Gillis, Jenniferb; Raboud, Janet M.b,c; Cooper, Curtisd; Hogg, Robert S.e,f; Montaner, Julio S.G.f,g; Burchell, Ann N.h,c; Loutfy, Mona R.i,j,k; Machouf, Nimal; Klein, Marina B.m; Tsoukas, Chris M.a; the Canadian Observational Cohort (CANOC) collaboration

doi: 10.1097/01.aids.0000432471.84497.bc
Clinical Science

Objective(s): We investigated the probability of transitioning in or out of the CD3+ T-cell homeostatic range during antiretroviral therapy, and we assessed the clinical impact of lost T-cell homeostasis (TCH) on AIDS-defining illnesses (ADIs) or death.

Design: Within the Canadian Observational Cohort (CANOC), we studied 4463 antiretroviral therapy (ART)-naive HIV-positive patients initiating combination ART (cART) between 2000 and 2010.

Methods: CD3+ trajectories were estimated using a four state Markov model. CD3+ T-cel percentage states were classified as follows: very low (<50%), low (50–64%), normal (65–85%), and high (>85%). Covariates associated with transitioning between states were examined. The association between CD3+ T-cell percentage states and time to ADI/death from cART initiation was determined using Cox proportional hazards models.

Results: A total of 4463 patients were followed for a median of 3 years. Two thousand, five hundred and eight (56%) patients never transitioned from their baseline CD3+ T-cell percentage state; 85% of these had normal TCH. In multivariable analysis, individuals with time-updated low CD4+ cell count, time-updated detectable viral load, older age, and hepatitis C virus (HCV) coinfection were less likely to maintain TCH. In the multivariable proportional hazards model, both very low and high CD3+ T-cell percentages were associated with increased risk of ADI/death [adjusted hazard ratio=1.91 (95% confidence interval, CI: 1.27–2.89) and hazard ratio=1.49 (95% CI: 1.13–1.96), respectively].

Conclusion: Patients with very low or high CD3+ T-cell percentages are at risk for ADIs/death. To our knowledge, this is the first study linking altered TCH and morbidity/mortality in cART-treated HIV-positive patients.

aMcGill University Health Centre, Montreal, Quebec

bToronto General Research Institute, University Health Network, Toronto

cDalla Lana School of Public Health, University of Toronto

dUniversity of Ottawa, The Ottawa Hospital Research Institute, Ottawa, Ontario

eSimon Fraser University, Burnaby

fBritish Columbia Centre for Excellence in HIV/AIDS, Vancouver

gDepartment of Medicine, University of British Columbia, Vancouver, British Columbia

hOntario HIV Treatment Network, Toronto

iDepartment of Medicine, University of Toronto

jWomen's Health Research Institute, Toronto

kMaple Leaf Medical Clinic, Toronto, Ontario

lClinique Médicale l’Actuel, Montreal

mMcGill University Health Centre, Division of Infectious Diseases and Chronic Viral Illness Service, Montreal, Quebec, Canada.

*The members of the CANOC Collaboration are listed in the Acknowledgements.

Correspondence to Patricia Ndumbi, Montreal General Hospital, 1650 Cedar Avenue, Room A5.140, Montreal, QC H3G 1A4, Canada. Tel: +1 514 934 1934x48035; fax: +1 514 937 1424; e-mail: patricia.ndumbi@mail.mcgill.ca

Received 25 March, 2013

Revised 20 June, 2013

Accepted 24 June, 2013

The data summarized in this paper were presented in part at the 20th Conference on Retroviruses and Opportunistic Infections – CROI (Abstract #M-193). The data were originally presented in part at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, July 2011 (Abstract MOPE203).

© 2013 Lippincott Williams & Wilkins, Inc.