Characteristics and determinants of T-cell phenotype normalization in HIV-1-infected individuals receiving long-term antiretroviral therapy.

Autor:	Ndumbi, P, Gillis, J, Raboud, J, Cooper, C, Hogg, RS, Montaner, JSG, Burchell, AN, Loutfy, MR, Machouf, N, Klein, MB, Tsoukas, C
Předmět:	HIV-positive persons LONGITUDINAL method RESEARCH funding PHENOTYPES HIGHLY active antiretroviral therapy PROPORTIONAL hazards models DATA analysis software DESCRIPTIVE statistics KAPLAN-Meier estimator CD4 lymphocyte count
Zdroj:	HIV Medicine; Mar2014, Vol. 15 Issue 3, p153-164, 11p
Abstrakt:	Objectives Although combination antiretroviral therapy ( cART) can restore CD4 T-cell numbers in HIV infection, alterations in T-cell regulation and homeostasis persist. We assessed the incidence and predictors of reversing these alterations with cART. Methods ART-naïve adults (n = 4459) followed within the Canadian Observational Cohort and exhibiting an abnormal T-cell phenotype ( TCP) prior to cART initiation were studied. Abnormal TCP was defined as having (1) a low CD4 T-cell count (< 532 cells/μ L), (2) lost T-cell homeostasis ( CD3 < 65% or > 85%) or (3) CD4: CD8 ratio dysregulation (ratio < 1.2). To thoroughly evaluate the TCP, CD4 and CD8 T-cell percentages and absolute counts were also analysed for a median duration of 3.14 years [interquartile range ( IQR) 1.48-5.47 years]. Predictors of TCP normalization were assessed using adjusted Cox proportional hazards models. Results At baseline, 96% of pateints had CD4 depletion, 32% had lost homeostasis and 99% exhibited ratio dysregulation. With treatment, a third of patients had normalized CD4 T-cell counts, but only 85 individuals (2%) had normalized their TCP. In a multivariable model adjusted for age, measurement frequency and baseline regimen, higher baseline CD4 T-cell counts and time-dependent viral suppression independently predicted TCP normalization [hazard ratio ( HR) for baseline CD4 T-cell count = 1.42 (1.31-1.54) per 100 cells/μ L increase; P ≤ 0.0001; HR for time-dependent suppressed viral load = 3.69 (1.58-8.61); P-value ≤ 0.01]. Conclusions Despite effective cART, complete TCP recovery occurred in very few individuals and was associated with baseline CD4 T-cell count and viral load suppression. HIV-induced alterations of the TCP are incompletely reversed by long-term ART. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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