BACKGROUND: Factors influencing the outcome of structured treatment interruptions (STIs) in HIV chronic infection are not fully elucidated. METHODS: In ISS-PART, 273 subjects were randomly assigned to arm A (137 assigned to continuous highly active antiretroviral therapy [HAART]) and arm B (136 assigned to 5 STIs of 1, 1, 2, 2, and 3 months' duration, each followed by 3 months of therapy). Main outcome measures were the proportion of subjects with a CD4 count >500 cells/mm, the rate of virologic failure, and the emergence of resistance at 24 months. RESULTS: The proportion of subjects with a CD4 count >500 cells/mm was higher in arm A than in arm B (86.5% vs. 69.1%; P = 0.0075). Pre-HAART CD4 cell count and male gender were independent predictors of a CD4 count >500 cells/mm in arm B. The overall risk of virologic failure was not increased in arm B; however, it was higher in the 38 subjects who had resistance mutations in the rebounding virus. Archived mutations at baseline and the use of a regimen that included an unboosted protease inhibitor (PI), compared with nonnucleoside reverse transcriptase inhibitor-based HAART, independently predicted the emergence of plasma mutations during STI (P = 0.002 for DNA mutations and P = 0.048 for PI-based HAART). CONCLUSIONS: Our results suggest that patients with preexisting mutations and treated with unboosted PI-based HAART should not be enrolled in studies of time-fixed treatment interruptions, being at higher risk of developing plasma mutations during STI and virologic failure at therapy reinstitution. © 2007 Lippincott Williams & Wilkins, Inc.
Determinants of virologic and immunologic outcomes in chronically HIV-infected subjects undergoing repeated treatment interruptions: The Istituto Superiore di Sanità-Pulsed Antiretroviral Therapy (ISS-PART) study / Palmisano, L.; Giuliano, M.; Bucciardini, R.; Fragola, V.; Andreotti, M.; Galluzzo, C. M.; Pirillo, M. F.; Weimer, L. E.; Arcieri, R.; Germinario, E. A. P.; Amici, R.; Mancini, M. G.; D'Arminio Monforte, A.; Castelli, F.; Caramello, P.; Vella, S.; Abrescia, N.; Figoni, M.; Viglietti, R.; Angarano, G.; Saracino, A.; Anselmo, M.; Antinori, A.; Sette, P.; Zaccarelli, M.; Liuzzi, G.; Arlotti, M.; Martelli, L. T.; Ortolani, P.; Bassetti, D.; Di Biagio, A.; Bisio, F.; Bellissima, P.; Branz, F.; Dorigoni, N.; Cadeo, G.; Vangi, D.; Bertelli, D.; Bergamasco, A.; Caggese, L.; Volonterio, A.; Orofino, G. C.; Carosella, S.; Gennero, L.; Caremani, M.; Tacconi, D.; Carosi, G.; Tomasoni, L.; Patroni, A.; Chiodo, F.; Borderi, M.; Calza, L.; Gritti, F.; Fasulo, G.; Chirianni, A.; Gargiulo, M.; Colomba, A.; Dalle Nogare, E. R.; Di Lorenzo, F.; Prestileo, T.; Bini, T.; Cicconi, P.; De Lalla, F.; Giordani, M. T.; De Stefano, C.; De Stefano, G.; Delia, S.; Ciardi, M.; Di Perri, G.; Sinicco, A.; Sales, P.; Dini, M.; Simeone, M.; Esposito, R.; Guaraldi, G.; Beghetto, B.; Fatuzzo, F.; La Rosa, R.; Ferrari, C.; Calzetti, C.; Ferraro, T.; Cosco, L.; Ghinelli, F.; Sighinolfi, L.; Guadagnino, V.; Caroleo, B.; Izzi, A.; Izzo, C.; Franco, A.; Lazzarin, A.; Castagna, A.; Fusetti, G.; Leoncini, F.; Pozzi, M.; Sbaragli, S.; Marzetti, M.; Magnani, G.; Bonazzi, L.; Barchi, E.; Zoboli, G.; Pintus, A.; Mandas, A.; Soddu, M. L.; Zucca, F.; Mannucci, P. M.; Gringeri, A.; Marani Toro, G.; Graziani, R. V.; Consorti, A.; Mazzotta, F.; Di Pietro, M.; Ble, C.; Meneghetti, F.; Sasset, L.; Cattelan, A. M.; Menichetti, F.; Savalli, E.; Mian, P.; Pristera, R.; Mignani, E.; Artioli, S.; Mura, M. S.; Mannazzu, M.; Narciso, P.; Bellagamba, R.; Orani, A.; Perini, P.; Ortona, L.; De Luca, A.; Murri, R.; Pagano, G.; Alessandrini, A.; Paladini, A.; Vinattieri, M. A.; Carbonai, S.; Pastore, G.; Ladina, N.; Tateo, M.; Piersantelli, N.; Penco, G.; Petrelli, E.; Balducci, M.; Pippi, L.; Gonnelli, A.; Puppo, F.; Murdaca, G.; Raise, E.; Pasquirucci, A.; Riccio, G.; Bartolacci, V.; Carrega, G.; Rizzardini, G.; Migliorino, G.; Russo, R.; Casentino, S.; Celesia, M.; Soranzo, M. L.; Macor, A.; Salassa, B.; Soscia, F.; Roberti, L.; Di Toro, M. T.; Stagno, A.; Beltrami, C.; Suter, F.; Maggiolo, F.; Ripamonti, D.; Tantimonaco, G.; Grisorio, B.; Tassara, A.; Rossi, P.; Tinelli, M.; Regazzetti, A.; Tirelli, U.; Voltaggio, G.; Cinelli, R.; Toti, M.; Baldari, M.; Carli, T.; Ricciardi, B.; Trezzi, M.; Vigevani, G. M.; Capetti, A.; Landonio, S.; Vullo, V.; Massetti, P.; Zauli, T.; Casolari, S.. - In: JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES. - ISSN 1525-4135. - 46:1(2007), pp. 39-47. [10.1097/QAI.0b013e31813e62e1]
Determinants of virologic and immunologic outcomes in chronically HIV-infected subjects undergoing repeated treatment interruptions: The Istituto Superiore di Sanità-Pulsed Antiretroviral Therapy (ISS-PART) study
Palmisano L.;Saracino A.;Zaccarelli M.;Arlotti M.;Chiodo F.;Ciardi M.;Guaraldi G.;Beghetto B.;Sighinolfi L.;Izzo C.;Pozzi M.;Pintus A.;Di Pietro M.;Menichetti F.;Macor A.;Baldari M.;Massetti P.;
2007
Abstract
BACKGROUND: Factors influencing the outcome of structured treatment interruptions (STIs) in HIV chronic infection are not fully elucidated. METHODS: In ISS-PART, 273 subjects were randomly assigned to arm A (137 assigned to continuous highly active antiretroviral therapy [HAART]) and arm B (136 assigned to 5 STIs of 1, 1, 2, 2, and 3 months' duration, each followed by 3 months of therapy). Main outcome measures were the proportion of subjects with a CD4 count >500 cells/mm, the rate of virologic failure, and the emergence of resistance at 24 months. RESULTS: The proportion of subjects with a CD4 count >500 cells/mm was higher in arm A than in arm B (86.5% vs. 69.1%; P = 0.0075). Pre-HAART CD4 cell count and male gender were independent predictors of a CD4 count >500 cells/mm in arm B. The overall risk of virologic failure was not increased in arm B; however, it was higher in the 38 subjects who had resistance mutations in the rebounding virus. Archived mutations at baseline and the use of a regimen that included an unboosted protease inhibitor (PI), compared with nonnucleoside reverse transcriptase inhibitor-based HAART, independently predicted the emergence of plasma mutations during STI (P = 0.002 for DNA mutations and P = 0.048 for PI-based HAART). CONCLUSIONS: Our results suggest that patients with preexisting mutations and treated with unboosted PI-based HAART should not be enrolled in studies of time-fixed treatment interruptions, being at higher risk of developing plasma mutations during STI and virologic failure at therapy reinstitution. © 2007 Lippincott Williams & Wilkins, Inc.
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