Clin Infect Dis. 2010 Aug 15;51(4):456-64.

Rate of CD4+ cell count increase over periods of viral load suppression: relationship with the number of previous virological failures.
Trotta MP, Cozzi-Lepri A, Ammassari A, Vecchiet J, Cassola G, Caramello P, Vullo V, Soscia F, Chiodera A, Ladisa N, Abeli C, Cauda R, Buonuomi AR, Antinori A, d'Arminio Monforte A; ICONA Foundation Study.

Collaborators (118)Moroni M, Carosi G, Cauda R, Chiodo F, d'Arminio Monforte A, Di Perri G, Galli M, Iardino R, Ippolito G, Lazzarin A, Panebianco R, Pastore G, Perno CF, Ammassari A, Antinori A, Arici C, Balotta C, Bonfanti P, Capobianchi MR, Castagna A, Ceccherini-Silberstein F, Cozzi-Lepri A, d'Arminio Monforte A, De Luca A, Gervasoni C, Girardi E, Lo Caputo S, Murri R, Mussini C, Puoti M, Torti C, Montroni M, Scalise G, Braschi MC, Riva A, Tirelli U, Martellotta F, Pastore G, Ladisa N, Suter F, Arici C, Chiodo F, Colangeli V, Fiorini C, Coronado O, Carosi G, Cristini G, Torti C, Minardi C, Bertelli D, Quirino T, Manconi PE, Piano P, Pizzigallo E, D'Alessandro M, Ghinelli F, Sighinolfi L, Leoncini F, Mazzotta F, Pozzi M, Lo Caputo S, Grisorio B, Ferrara S, Pagano G, Cassola G, Alessandrini A, Piscopo R, Soscia F, Tacconi L, Orani A, Perini P, Chiodera F, Castelli P, Moroni M, Lazzarin A, Rizzardini G, Caggese L, d'Arminio Monforte A, Galli A, Merli S, Pastecchia C, Moioli MC, Esposito R, Mussini C, Abrescia N, Chirianni A, De Marco M, Viglietti R, Ferrari C, Pizzaferri P, Filice G, Bruno R, Magnani G, Ursitti MA, Arlotti M, Ortolani P, Cauda R, Antinori A, Antonucci G, Narciso P, Vullo V, De Luca A, Zaccarelli M, Acinapura R, De Longis P, Trotta MP, Lichtner M, Carletti F, Mura MS, Mannazzu M, Caramello P, Di Perri G, Orofino GC, Sciandra M, Raise E, Ebo F, Pellizzer G, Buonfrate D.
Clinical Department, National Institute for Infectious Diseases L. Spallanzani, Roma, Italy. mariapaola.trotta@inmi.it

Comment in:

Clin Infect Dis. 2010 Aug 15;51(4):465-7.

Abstract
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 months, 51 months, and 45 months in subjects without evidence of previous virological failure, or 1, 2, or > or = 3 previous virologically failed regimens, respectively (P < .001, by log-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 antiretrovirals.

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 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.



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