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, A. D.; 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, C. F.; 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, M. R.; 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.; E 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, A. P.; Rizzardini, G.; Ridolfo, A. L.; Piolini, R.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Tincati, C.; Puzzolante, C.; Abrescia, N.; Chirianni, A.; Guida, M. G.; Gargiulo, M.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Vullo, V.; D'Avino, A.; Gallo, L.; Acinapura, R.; Capozzi, M.; Libertone, R.; Tebano, G.; Cattelan, A.; Sasset, L.; Mura, M. S.; Rossetti, B.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.

doi:10.1016/S2352-3018(15)00006-5

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. Funding: AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp & Dohme, ViiV Italy.