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: firstname.lastname@example.org
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).