Journal Article

Rate of CD4<sup>+</sup> Cell Count Increase over Periods of Viral Load Suppression: Relationship with the Number of Previous Virological Failures

Maria Paola Trotta, Alessandro Cozzi-Lepri, Adriana Ammassari, Jacopo Vecchiet, Giovanni Cassola, Pietro Caramello, Vincenzo Vullo, Fabrizio Soscia, Alessandro Chiodera, Nicoletta Ladisa, Clara Abeli, Roberto Cauda, Anna Rita Buonuomi, Andrea Antinori and Antonella d'Arminio Monforte

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 51, issue 4, pages 456-464
Published in print August 2010 | ISSN: 1058-4838
Published online August 2010 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/655151
Rate of CD4+ Cell Count Increase over Periods of Viral Load Suppression: Relationship with the Number of Previous Virological Failures

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Background. Although the kinetics of CD4+ cell counts have been extensively studied in antiretroviral-naive HIV-infected patients, data on individuals who have failed combination antiretroviral therapy (cART) are lacking.

Methods. This analysis was based on the ICONA Foundation Study. Subjects with ≥1 episode of viral suppression after starting first-line cART were included (n = 3537). Following a viral rebound, patients who achieved another episode of viral suppression could reenter the analysis. The percentage of patients with an increase in CD4+ cell count >300 cells/mm3 was estimated using Kaplan-Meier techniques; the rate of CD4+ cell count increase per year was estimated using a multivariable, multilevel linear model with fixed effects of intercept and slope. Multivariable models were also fitted to include several covariates.

Results. The median time to reach a CD4+ cell count increase >300 cells/mm3 from baseline was significantly associated with the number of failed regimens: 34 months, 41 months, 51 months, and 45 months in subjects without evidence of previous virological failure, or 1, 2, or ≥3 previous virologically failed regimens, respectively (P < .001, by log-rank test). The annual estimated increases in CD4+ cell count were 36 cells/mm3 (95% confidence interval [CI], 34–38 cells/mm3), 28 cells/mm3 (95% CI, 11–21 cells/mm3), 31 cells/mm3 (95% CI, 26–36 cells/ mm3), and 26 cells/mm3 (95% CI, 18–33 cells/mm3), respectively. Differences in the annual CD4+ cell count increase were observed between specific antiretrovirals.

Conclusions. Subjects with ≥1 virological failure took a longer time to reach a CD4+ cell count >300 cell/ mm3 and had a slower annual increase than those without virological failure. Efforts should be made to optimize first-line cART, because this represents the best chance of achieving an effective CD4+ response.

Journal Article.  4310 words.  Illustrated.

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

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