Objectives: The objective of this study was to assess the 48-week virological efficacy of atazanavir/ritonavir (ATV/r) monotherapy vs. ATV/r along with two nucleoside reverse transcriptase (NRTIs) in HIV-1 treated individuals with HIV-RNA less than 50 copies/ml. Methods: A multicentre, randomized, open-label, noninferiority trial. HIV-1 treated individuals on ATV/r 300/100mg along with two NRTIs were randomized to receive ATV/r monotherapy or to maintain their antiretroviral regimen. The primary endpoint was the confirmed viral rebound (CVR: Two consecutive HIV-RNA >50 copies/ml) or treatment discontinuation for any reason. Individuals who experienced CVR on ATV/r monotherapy reintroduced NRTIs and discontinued the study if HIV-RNA was more than 50 copies/ml after 12 weeks since reintensification. Results: One hundred and three patients enrolled. By week 48, 11 patients in ATV/r arm and two in ATV/r along with twoNRTIs experienced CVR; four (8%) patients in ATV/r and eight (15%) in ATV/r along with twoNRTIs discontinued. At the 48-week primary efficacy analysis (re-intensification=failure), treatment success was73%inATV/r armand85%in ATV/r along with two NRTIs [difference 12.1%, 95% confidence interval (95% CI)27.8 to 2.1]. According to the analysis considering re-intensification is equal to success, treatment success was 92%in ATV/r armand 85%in the ATV/r along with twoNRTIs arm (difference 7.5%, 95%CI4.7 to 19.8). At CVR, no mutation was observed in ATV/r arm and reintensification with NRTIs was effective in all individuals. Overall, Grade 3-4 (P=0.003) and grade 3-4 drug-related (P=0.027) adverse events were less frequent in ATV/r arm. A significant increase in total and low-density lipoprotein (LDL)-cholesterol was observed as well as a significant improvement in high-density lipoprotein (HDL)- cholesterol, fasting glucose, liver fibrosis and alkaline phosphatase was observed in ATV/r monotherapy in comparison with ATV/r along with two NRTIs. Conclusion: ATV/r monotherapy treatment simplification showed lower virological efficacy in comparison with maintaining triple therapy; NRTIs reintroduction was effective in all the individuals.
Castagna, A., Spagnuolo, V., Galli, L. M., Vinci, C., Nozza, S., Carini, E., Monforte, A. D., Montella, F., Antinori, A., Di Biagio, A., Rusconi, S., Lazzarin, A., Viscoli, C., Parisini, A., Prinapori, R., Mazzotta, F., Lo Caputo, S., Di Pietro, M. L., D'Arminio-Monforte, A., Tincati, C., Bini, T., Merlini, E., Puoti, M., Moioli, M., Montella, M., Di Sora, F., Ammassari, A., Ottou, S., Cauda, R., Di Giambenedetto, S., Galli, M., Franzetti, M., Rizzardini, G., Capetti, A., Cossarini, F., Gianotti, N., Mussini, C., Guaraldi, G., Simplification to atazanavir/ritonavir monotherapy for HIV-1 treated individuals on virological suppression: 48-week efficacy and safety results, <<AIDS>>, 2014; 28 (15): 2269-2279. [doi:10.1097/QAD.0000000000000407] [http://hdl.handle.net/10807/193897]
Simplification to atazanavir/ritonavir monotherapy for HIV-1 treated individuals on virological suppression: 48-week efficacy and safety results
Galli, Lavinia Maddalena;Carini, Elettra;Montella, Francesco;Antinori, Armando;Di Biagio, Anna;Di Pietro, Maria Luisa;Di Sora, Fiorella;Cauda, Roberto;Di Giambenedetto, Simona;
2014
Abstract
Objectives: The objective of this study was to assess the 48-week virological efficacy of atazanavir/ritonavir (ATV/r) monotherapy vs. ATV/r along with two nucleoside reverse transcriptase (NRTIs) in HIV-1 treated individuals with HIV-RNA less than 50 copies/ml. Methods: A multicentre, randomized, open-label, noninferiority trial. HIV-1 treated individuals on ATV/r 300/100mg along with two NRTIs were randomized to receive ATV/r monotherapy or to maintain their antiretroviral regimen. The primary endpoint was the confirmed viral rebound (CVR: Two consecutive HIV-RNA >50 copies/ml) or treatment discontinuation for any reason. Individuals who experienced CVR on ATV/r monotherapy reintroduced NRTIs and discontinued the study if HIV-RNA was more than 50 copies/ml after 12 weeks since reintensification. Results: One hundred and three patients enrolled. By week 48, 11 patients in ATV/r arm and two in ATV/r along with twoNRTIs experienced CVR; four (8%) patients in ATV/r and eight (15%) in ATV/r along with twoNRTIs discontinued. At the 48-week primary efficacy analysis (re-intensification=failure), treatment success was73%inATV/r armand85%in ATV/r along with two NRTIs [difference 12.1%, 95% confidence interval (95% CI)27.8 to 2.1]. According to the analysis considering re-intensification is equal to success, treatment success was 92%in ATV/r armand 85%in the ATV/r along with twoNRTIs arm (difference 7.5%, 95%CI4.7 to 19.8). At CVR, no mutation was observed in ATV/r arm and reintensification with NRTIs was effective in all individuals. Overall, Grade 3-4 (P=0.003) and grade 3-4 drug-related (P=0.027) adverse events were less frequent in ATV/r arm. A significant increase in total and low-density lipoprotein (LDL)-cholesterol was observed as well as a significant improvement in high-density lipoprotein (HDL)- cholesterol, fasting glucose, liver fibrosis and alkaline phosphatase was observed in ATV/r monotherapy in comparison with ATV/r along with two NRTIs. Conclusion: ATV/r monotherapy treatment simplification showed lower virological efficacy in comparison with maintaining triple therapy; NRTIs reintroduction was effective in all the individuals.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
