J Antimicrob Chemother. 2012 May;67(5):1224-7.

Viral tropism by geno2pheno as a tool for predicting CD4 decrease in HIV-1-infected naive patients with high CD4 counts.
Nozza S, Canducci F, Galli L, Cozzi-Lepri A, Capobianchi MR, Ceresola ER, Narciso P, Libertone R, Castelli P, Moioli M, D'Arminio Monforte A, Castagna A; ICONA Foundation.

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 C, Ammassari A, Antinori A, Arici C, Balotta C, Bonfanti P, Capobianchi M, 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 M, 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 P, 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 M, Esposito R, Mussini C, Abrescia N, Chirianni A, De Marco M, Viglietti R, Ferrari C, Pizzaferri P, Filice G, Bruno R, Magnani G, Ursitti M, 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 M, Lichtner M, Carletti F, Mura M, Mannazzu M, Caramello P, Di Perri G, Orofino G, Sciandra M, Raise E, Ebo F, Pellizzer G, Buonfrate D.

SourceSan Raffaele Scientific Institute, Milan, Italy. silvia.nozza@hsr.it

Abstract
OBJECTIVES: To investigate the value of tropism (determined by genotypic testing) to predict CD4 depletion in HIV-infected antiretroviral-naive patients with high CD4 counts.

METHODS: Viral tropism was determined by geno2pheno (false positive rate = 10%) in 223 HIV-infected subjects naive to antiretrovirals with CD4 count ≥350 cells/μL and HIV-RNA >500 copies/mL enrolled in the ICONA Foundation Study for whom a stored plasma sample (baseline) was retrospectively tested. We monitored CD4 cell count and identified predictors of decline before antiretroviral therapy initiation, applying a mixed linear model with covariates (age, gender, tropism, HIV risk factor, calendar year of HIV infection, months from HIV diagnosis to baseline, hepatitis C virus status, CD4 and HIV-RNA at sample collection and duration of follow-up).

RESULTS: Two hundred and twenty-three subjects met the eligibility criteria; 137 (61%) were male and the median age was 35 (31-40) years. Median follow-up was 16.4 (3.2-37.2) months. Median CD4 decrease during follow-up was -157 (-278 to -13) cells/μL. At baseline, 192 (86%) subjects were defined as harbouring R5 virus and 31 (14%) non-R5. Median CD4 count was 571 (458-729) cells/μL and median HIV-RNA was 4.08 (3.57-4.55) log(10) copies/mL. At multivariable analysis, a greater mean CD4 decrease was associated with non-R5 viral tropism (-159.9 ± 12.22, P = 0.0002) at baseline. Other significant covariates were female gender, older age, intravenous drug use, longer duration of follow-up, and higher CD4 cell count and higher HIV-RNA at sample collection.

CONCLUSIONS: In patients with CD4 counts ≥350 cells/μL, non-R5 viral tropism by geno2pheno is predictive of CD4 decrease independent of their viral set point and CD4 counts.


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