Rate of CD4+ cell count increase over periods of viral load suppressione: relationship with the number of previous virological failures.

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 > or = 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/mm(3) 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/mm(3) from baseline was significantly associated with the number of failed regimens: 34 months, 41 monthis, 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 long-rank test). The annual estimated increases in CD4 (+) cell count were 36 cells/mm(3) (95% confidence interval (CI), 34-38 cells/mm(3)), 28 cells/mm(3) (95% CI, 11-21 cells/mm (3)), 31 cells/mm(3) (95% CI, 26-36 cells/mm(3)), and 26 cells/mm(3) (95% CI, 18-33 cells/mm (3)), respectively. Differences in the annual CD4(+) cell count increase were observed between specific antiretroviral. CONCLUSIONS: Subjects with > or = 1 virological failure took a longer time to reach a CD4 (+) cell count > 300 cell/mm(3) and had a slower annual increae than those without virological failure: Efforts should be made to optimize first-line cART, because this represents the best change of achieving an effective CD4(+) response