Journal Article

Incomplete Peripheral CD4<sup>+</sup> Cell Count Restoration in HIV-Infected Patients Receiving Long-Term Antiretroviral Treatment

Colleen F. Kelley, Christina M. R. Kitchen, Peter W. Hunt, Benigno Rodriguez, Frederick M. Hecht, Mari Kitahata, Heide M. Crane, James Willig, Michael Mugavero, Michael Saag, Jeffrey N. Martin and Steven G. Deeks

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 48, issue 6, pages 787-794
Published in print March 2009 | ISSN: 1058-4838
Published online March 2009 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/597093
Incomplete Peripheral CD4+ Cell Count Restoration in HIV-Infected Patients Receiving Long-Term Antiretroviral Treatment

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Background.Although antiretroviral therapy has the ability to fully restore a normal CD4+ cell count (>500 cells/mm3) in most patients, it is not yet clear whether all patients can achieve normalization of their CD4+ cell count, in part because no study has followed up patients for >7 years.

Methods.Three hundred sixty-six patients from 5 clinical cohorts who maintained a plasma human immunodeficiency virus (HIV) RNA level <1000 copies/mL for at least 4 years after initiation of antiretroviral therapy were included. Changes in CD4+ cell count were evaluated using mixed-effects modeling, spline-smoothing regression, and Kaplan-Meier techniques.

Results.The majority (83%) of the patients were men. The median CD4+ cell count at the time of therapy initiation was 201 cells/mm3 (interquartile range, 72–344 cells/mm3), and the median age was 47 years. The median follow-up period was 7.5 years (interquartile range, 5.5–9.7 years). CD4+ cell counts continued to increase throughout the follow-up period, albeit slowly after year 4. Although almost all patients (95%) who started therapy with a CD4+ cell count ⩾300 cells/mm3 were able to attain a CD4+ cell count ⩾500 cells/mm3, 44% of patients who started therapy with a CD4+ cell count <100 cells/mm3 and 25% of patients who started therapy with a CD4+ cell count of 100–200 cells/mm3 were unable to achieve a CD4+ cell count >500 cells/mm3 over a mean duration of follow-up of 7.5 years; many did not reach this threshold by year 10. Twenty-four percent of individuals with a CD4+ cell count <500 cells/mm3 at year 4 had evidence of a CD4+ cell count plateau after year 4. The frequency of detectable viremia (“blips”) after year 4 was not associated with the magnitude of the CD4+ cell count change.

Conclusions.A substantial proportion of patients who delay therapy until their CD4+ cell count decreases to <200 cells/mm3 do not achieve a normal CD4+ cell count, even after a decade of otherwise effective antiretroviral therapy. Although the majority of patients have evidence of slow increases in their CD4+ cell count over time, many do not. These individuals may have an elevated risk of non–AIDS-related morbidity and mortality.

Journal Article.  4653 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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