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Pre-ART HIV-1 DNA in CD4+ T cells correlates with baseline VIRO-immunological status and outcome in patients under first-line ART

Journal of Antimicrobial Chemotherapy, ISSN: 1460-2091, Vol: 73, Issue: 12, Page: 3460-3470
2018
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Article Description

Objectives We evaluated the association between pre-ART HIV DNA and HIV-infected participant characteristics at baseline as well as with their response to first-line ART. Methods Four hundred and thirty-three patients from the ICONA cohort, starting first-line ART after the year 2000, were analysed. Pre-ART HIV DNA was quantified with the modified COBAS TaqMan HIV-1 Test and normalized by CD4+ T cells. Linear correlation between pre-ART HIV DNA and other continuous markers (HIV RNA, CD4 count, markers of inflammation and coagulation) at baseline was evaluated by means of Pearson correlation coefficient and a linear regression model. Survival analyses and Cox regression models were used to study the association between pre-ART HIV DNA and time to VIRO-immunoclinical events. Results Pre-ART HIV DNA [median (IQR): 10 € 702 (3397-36 € 632) copies/10 6 CD4+ T cells] was correlated with pre-ART HIV RNA [R 2 = +0.44, (P < 0.0001)], CD4+ T cells [R 2 = '0.58, (P < 0.0001)] and CD4/CD8 ratio [R 2 = '0.48, (P < 0.0001)], while weaker correlations were observed with CD8+ T cells (R 2 = '0.20, P = 0.01), IL-6 (R 2 = +0.16, P = 0.002) and soluble CD14 (R 2 = +0.09, P = 0.05). Patients with higher pre-ART HIV DNA showed lower rate and delayed VIROlogical response (defined as HIV RNA ≤50 copies/mL), compared with those having lower HIV DNA (67.2% for >10 € 000, 81.1% for 1000-10 € 000 and 86.4% for 10-1000 copies/10 6 CD4+ T cells; P = 0.0004). Higher pre-ART HIV DNA was also correlated with increased risk of VIROlogical rebound (defined as HIV RNA >50 copies/mL) by 24 months (17.2% for >10 € 000, 7.4% for 1000-10 € 000 and 4.3% for 10-1000 copies/10 6 CD4+ T cells; P = 0.0048). Adjusted HRs of all VIROlogical rebound definitions confirmed these findings (P ≤ 0.02). Conclusions Pre-ART HIV DNA, along with HIV RNA and CD4+ T cell count, should be considered as a new staging marker to better identify people at lower (or higher) risk of viral rebound following achievement of VIROlogical suppression (≤50 copies/mL).

Bibliographic Details

Ceccherini-Silberstein, Francesca; Cozzi Lepri, Alessandro; Alteri, Claudia; Merlini, Esther; Surdo, Matteo; Marchetti, Giulia; Capobianchi, Maria Rosaria; De Luca, Andrea; Gianotti, Nicola; Viale, Pierluigi; Andreoni, Massimo; Antinori, Andrea; Perno, Carlo Federico; d’Arminio Monforte, Antonella; d’Arminio Monforte, A; Antinori, A; Castagna, A; Castelli, F; Cauda, R; Di Perri, G; Galli, M; Iardino, R; Ippolito, G; Lazzarin, A; Marchetti, G C; Perno, C F; Rezza, G; von Schloesser, F; Viale, P; Ceccherini-Silberstein, F; Cozzi-Lepri, A; Girardi, E; Lo Caputo, S; Mussini, C; Puoti, M; Andreoni, M; Ammassari, A; Balotta, C; Bandera, A; Bonfanti, P; Bonora, S; Borderi, M; Calcagno, A; Calza, L; Capobianchi, M R; Cingolani, A; Cinque, P; De Luca, A; Di Biagio, A; Gianotti, N; Gori, A; Guaraldi, G; Lapadula, G; Lichtner, M; Madeddu, G; Maggiolo, F; Marchetti, G; Marcotullio, S; Monno, L; Nozza, S; Quiros Roldan, E; Rossotti, R; Rusconi, S; Santoro, M M; Saracino, A; Zaccarelli, M; Fanti, I; Galli, L; Lorenzini, P; Rodano, A; Shanyinde, M; Tavelli, A; Carletti, F; Carrara, S; Di Caro, A; Graziano, S; Petrone, F; Prota, G; Quartu, S; Truffa, S; Giacometti, A; Costantini, A; Barocci, V; Angarano, G; Santoro, C; Suardi, C; Donati, V; Verucchi, G; Minardi, C; Quirino, T; Abeli, C; Manconi, P E; Piano, P; Cacopardo, B; Celesia, B; Vecchiet, J; Falasca, K; Sighinolfi, L; Segala, D; Blanc, P; Vichi, F; Cassola, G; Viscoli, C; Alessandrini, A; Bobbio, N; Mazzarello, G; Mastroianni, C; Pozzetto, I; Molteni, C; Chiodera, A; Milini, P; Nunnari, G; Pellicanò, G; Rizzardini, G; Moioli, M C; Piolini, R; Ridolfo, A L; Salpietro, S; Tincati, C; Puzzolante, C; Chirianni, A; Borgia, G; Esposito, V; Orlando, R; Bonadies, G; Di Martino, F; Gentile, I; Maddaloni, L; Cattelan, A M; Marinello, S; Cascio, A; Colomba, C; Baldelli, F; Schiaroli, E; Parruti, G; Sozio, F; Magnani, G; Ursitti, M A; Acinapura, R; Baldin, G; Capozzi, M; Cicalini, S; Cristaudo, A; Fontanelli Sulekova, L; Iaiani, G; Latini, A; Mastrorosa, I; Plazzi, M M; Savinelli, S; Vergori, A; Vullo, V; Cecchetto, M; Viviani, F; Bagella, P; Rossetti, B; Franco, A; Fontana Del Vecchio, R; Francisci, D; Di Giuli, C; Caramello, P; Orofino, G C; Sciandra, M; Bassetti, M; Londero, A; Pellizzer, G; Manfrin, V; Starnini, G; Ialungo, A; ICONA Foundation Study Group

Oxford University Press (OUP)

Pharmacology, Toxicology and Pharmaceutics; Medicine

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