Durability of different initial regimens in HIV-infected patients starting antiretroviral therapy with CD4+ counts <200 cells/mm3 and HIV-RNA >5 log10 copies/mL

Gianotti, N.; Lorenzini, P.; Cozzi-Lepri, A.; De Luca, A.; Madeddu, G.; Sighinolfi, L.; Pinnetti, C.; Santoro, C.; Meraviglia, P.; Mussini, C.; Antinori, A.; D'Arminio Monforte, A.; Andreoni, M.; Angarano, G.; 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.; Bandera, A.; Bonfanti, P.; Bonora, S.; Borderi, M.; Calcagno, A.; Calza, L.; Capobianchi, M. R.; Cingolani, A.; Cinque, P.; Di Biagio, A.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Nozza, S.; Quiros Roldan, E.; Rossotti, R.; Rusconi, S.; Saracino, A.; Zaccarelli, M.; Fanti, I.; 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.; Valeriani, C.; Suardi, C.; Donati, V.; Verucchi, G.; Quiros, E.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Cacopardo, B.; Celesia, B.; Vecchiet, J.; Falasca, K.; Segala, D.; Mazzotta, F.; Vichi, F.; Cassola, G.; Viscoli, C.; Alessandrini, A.; Bobbio, N.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Chiodera, A.; Rizzardini, G.; Ridolfo, A. L.; Piolini, R.; Carenzi, L.; Moioli, M. C.; Tincati, C.; Puzzolante, C.; Abrescia, N.; Chirianni, A.; Borgia, G.; Di Martino, F.; Maddaloni, L.; Gentile, I.; Orlando, R.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Vullo, V.; Cristaudo, A.; Baldin, G.; Cicalini, S.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Savinelli, S.; Latini, A.; Cecchetto, M.; Viviani, F.; Mura, M. S.; Rossetti, B.; Caramello, P.; C Orofino, G.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.

doi:10.1093/jac/dkz237

Objectives: Our aim was to investigate the durability of different initial regimens in patients starting ART with CD4+ counts <200 cells/mm3 and HIV-RNA >5 log10 copies/mL. Methods: This was a retrospective study of HIV-infected patients prospectively followed in the ICONA cohort. Those who started ART with boosted protease inhibitors (bPIs), NNRTIs or integrase strand transfer inhibitors (InSTIs), with CD4+ <200 cells/mm3 and HIV-RNA >5 log10 copies/mL, were included. The primary endpoint was treatment failure (TF), a composite endpoint defined as virological failure (VF, first of two consecutive HIV-RNA >50 copies/mL after 6 months of treatment), discontinuation of class of the anchor drug or death. Independent associations were investigated by Poisson regression analysis in a model including age, gender, mode of HIV transmission, CDC stage, HCV and HBV co-infection, pre-treatment HIV-RNA, CD4+ count and CD4+/CD8+ ratio, ongoing opportunistic disease, fibrosis FIB-4 index, estimated glomerular filtration rate, haemoglobin, platelets, neutrophils, calendar year of ART initiation, anchor drug class (treatment group) and nucleos(t)ide backbone. Results: A total of 1195 patients fulfilled the inclusion criteria: 696 started ART with a bPI, 315 with an InSTI and 184 with an NNRTI. During 2759 person-years of follow up, 642 patients experienced TF. Starting ART with bPIs [adjusted incidence rate ratio (aIRR) (95% CI) 1.62 (1.29-2.03) versus starting with NNRTIs; P<0.001] and starting ART with InSTIs [aIRR (95% CI) 0.68 (0.48-0.96) versus starting with NNRTIs; P=0.03] were independently associated with TF. Conclusions: In patients starting ART with <200 CD4+ cells/mm3 and >5 log10 HIV-RNA copies/mL, the durability of regimens based on InSTIs was longer than that of NNRTI- and bPI-based regimens.