Background: In patients with HIV, immune reconstitution after antiretroviral therapy (ART) is often incomplete. We assessed the probability of patients reaching a CD4/CD8 ratio of 1 or more after the start of ART and its association with the onset of non-AIDS-defining events and death. Methods: We did an analysis of the ICONA cohort, which recruited treatment-naive patients with HIV in Italy. We included participants in the cohort who started ART, reached an undetectable viral load (≤80 copies per mL), and had a CD4/CD8 ratio of less than 0·8 at the time of an undetectable viral load. We defined ratio normalisation in patients as two consecutive values of 1 or more. We used Kaplan-Meier curves to estimate the cumulative probability of ratio normalisation. We then used Poisson regression models to identify factors independently associated with normalisation and with progression to non-AIDS-defining events or death. Findings: We included 3236 participants, enrolled between Jan 22, 1997, and Feb 25, 2013. At the start of ART, median CD4/CD8 ratio in our population was 0·39 (IQR 0·26-0·55). 458 (14%) patients reached a CD4/CD8 ratio of 1 or more; the estimated probability of normalisation was 4·4% (95% CI 3·7-5·2) by 1 year from baseline, 11·5% (10·2-13·0) by 2 years, and 29·4% (26·7-32·4) by 5 years. Factors associated with normalisation were high pre-ART CD4 cell counts, a high CD4/CD8 ratio at baseline, and negative cytomegalovirus serological findings. The incidence rate of non-AIDS-defining events for patients with a CD4/CD8 ratio of less than 0·30 (4·2 per 100 patient-years, 95% CI 3·4-5·3) was double that for those with a ratio of 0·30-0·45 (2·3, 2·1-2·5) or more than 0·45 (2·2, 1·7-2·9). A ratio of less than 0·30 was independently associated with an increased risk of non-AIDS-defining events or death compared with one of more than 0·45. Interpretation: Few patients had normalised CD4/CD8 ratios, even though they had viral suppression. Low ratios were associated with increased risk of serious events and deaths. The CD4/CD8 ratio could be used by clinicians to identity patients at risk of non-AIDS-related events.

CD4/CD8 ratio normalisation and non-AIDS-related events in individuals with HIV who achieve viral load suppression with antiretroviral therapy: An observational cohort study / Mussini, C; Lorenzini, P; Cozzi-Lepri, A; Lapadula, G; Marchetti, G; Nicastri, E; Cingolani, A; Lichtner, M; Antinori, A; Gori, A; Monforte, Ad; Moroni, M; Andreoni, M; Angarano, G; d'Arminio Monforte, A.; Castelli, F; Cauda, R; Di Perri, G; Galli, M; Iardino, R; Ippolito, G; Lazzarin, A; Perno, Cf; von Schloesser, F; Viale, P; Castagna, A; Ceccherini-Silberstein, F; Girardi, E; Lo Caputo, S; Puoti, M; Ammassari, A; Balotta, C; Bonfanti, P; Bonora, S; Borderi, M; Capobianchi, Mr; Cinque, P; De Luca, A; Di Biagio, A; Gianotti, N; Guaraldi, G; Madeddu, G; Maggiolo, F; Marcotullio, S; Monno, L; Quiros Roldan, E; Rusconi, S; Saracino, A; Cicconi, P; Fanti Galli, I; Tavelli, A; Giacometti, A; Costantini, A; Mazzoccato, S; Santoro, C; Suardi, C; Vanino, E; Verucchi, G; Minardi, C; Quirino, T; Abeli, C; Manconi, P; Piano, P; Vecchiet, J; Falasca, K; Sighinolfi, L; Segala, D; Mazzotta, F; Cassola, G; Viscoli, C; Alessandrini, A; Piscopo, R; Mazzarello, G; Mastroianni, C; Belvisi, V; Caramma, I; Chiodera, A; Castelli, Ap; Rizzardini, G; Ridolfo, Al; Piolini, R; Salpietro, S; Carenzi, L; Moioli, Mc; Tincati, C; Puzzolante, C; Abrescia, N; Chirianni, A; Guida, Mg; Gargiulo, M; Baldelli, F; Francisci, D; Parruti, G; Ursini, T; Magnani, G; Ursitti, Ma; Vullo, V; D'Avino, A; Gallo, L; Acinapura, R; Capozzi, M; Libertone, R; Tebano, G; Cattelan, A; Sasset, L; Mura, Ms; Rossetti, B; Caramello, P; Orofino, Gc; Sciandra, M; Bassetti, M; Londero, A; Pellizzer, G; Manfrin, V. - In: THE LANCET. HIV. - ISSN 2405-4704. - 2:3(2015), pp. 98-106. [10.1016/S2352-3018(15)00006-5]

CD4/CD8 ratio normalisation and non-AIDS-related events in individuals with HIV who achieve viral load suppression with antiretroviral therapy: An observational cohort study

Madeddu, G;
2015

Abstract

Background: In patients with HIV, immune reconstitution after antiretroviral therapy (ART) is often incomplete. We assessed the probability of patients reaching a CD4/CD8 ratio of 1 or more after the start of ART and its association with the onset of non-AIDS-defining events and death. Methods: We did an analysis of the ICONA cohort, which recruited treatment-naive patients with HIV in Italy. We included participants in the cohort who started ART, reached an undetectable viral load (≤80 copies per mL), and had a CD4/CD8 ratio of less than 0·8 at the time of an undetectable viral load. We defined ratio normalisation in patients as two consecutive values of 1 or more. We used Kaplan-Meier curves to estimate the cumulative probability of ratio normalisation. We then used Poisson regression models to identify factors independently associated with normalisation and with progression to non-AIDS-defining events or death. Findings: We included 3236 participants, enrolled between Jan 22, 1997, and Feb 25, 2013. At the start of ART, median CD4/CD8 ratio in our population was 0·39 (IQR 0·26-0·55). 458 (14%) patients reached a CD4/CD8 ratio of 1 or more; the estimated probability of normalisation was 4·4% (95% CI 3·7-5·2) by 1 year from baseline, 11·5% (10·2-13·0) by 2 years, and 29·4% (26·7-32·4) by 5 years. Factors associated with normalisation were high pre-ART CD4 cell counts, a high CD4/CD8 ratio at baseline, and negative cytomegalovirus serological findings. The incidence rate of non-AIDS-defining events for patients with a CD4/CD8 ratio of less than 0·30 (4·2 per 100 patient-years, 95% CI 3·4-5·3) was double that for those with a ratio of 0·30-0·45 (2·3, 2·1-2·5) or more than 0·45 (2·2, 1·7-2·9). A ratio of less than 0·30 was independently associated with an increased risk of non-AIDS-defining events or death compared with one of more than 0·45. Interpretation: Few patients had normalised CD4/CD8 ratios, even though they had viral suppression. Low ratios were associated with increased risk of serious events and deaths. The CD4/CD8 ratio could be used by clinicians to identity patients at risk of non-AIDS-related events.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11388/45950
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