Background: Nucleos(t)ide reverse transcriptase inhibitors (NRTI) toxicity may represent a threat for long-term success of combined antiretroviral therapy. Some studies have suggested a possible improvement of NRTI-related toxicity after switching to NRTI-sparing regimens. Objectives: We aimed to explore the efficacy and tolerability of switching to darunavir/ritonavir (DRV/r) plus raltegravir (RAL) while having a viral load (VL) ≤50 copies/mL in the clinical setting. Study design: Treatment-experienced HIV 1-infected patients enrolled in the ICONA Foundation Study cohort were included if they switched their current regimen to DRV/r + RAL with a HIV-RNA ≤50 copies/mL. Different definitions of virological failure (VF) and treatment failure (TF) were employed. Kaplan–Meier curves and Cox regression models were performed to estimate time to event probability. Results: We included 72 HIV-infected patients, 22 (31%) of these were female, 31 (43%) men who have sex with men (MSM) amd 15 (21%) had hepatitis co-infections. Median age was 44 (IQR: 35-50) years amd CD4 count was 389 (IQR 283-606) cells/mmc. Median follow-up time for TF was 24 (IQR 9–31) months. Twenty-five discontinuations occurred (60% simplifications); only 2 (8%) were toxicity-driven (lipid elevations). The probability of VF (confirmed VL >50 copies/mL) was estimated at 7% [95% confidence interval (CI) 1–13%] by 12 and 9% (95% CI 2–16%) by 24 months. When considering TF, we found a probability of stop/intensification/single VL > 200 copies/mL of 13% (95% CI 1–17%) and 22% (95% CI 11–33%) by 12 and 24 months. Female gender (adjusted relative hazard, ARH = 0.10; 95% CI 0.01–0.74; p = 0.024) and older age (AHR = 0.50 per 10 years older; 95% CI 0.25–0.99; p = 0.045) were associated with a lower risk of TF. A previous PI failure was strongly associated with TF (AHR = 52.6, 95% CI 3.6–779; p = 0.004). Conclusions: DRV/r + RAL is a valuable NRTI-sparing option, especially in female and older patients, with a relatively low risk of VF and good tolerability after 2 years since start in an ART-experienced population. However, previous PI-failure should be a limiting factor for this strategy.

Madeddu, G., Rusconi, S., Cozzi Lepri, A., Di Giambenedetto, S., Bonora, S., Carbone, A., De Luca, A., Gianotti, N., Di Biagio, A., Antinori, A., D’arminio Monforte, A., Andreoni, M., Angarano, G., Antinori, 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., Cozzi Lepri, A., Girardi, E., Lo Caputo, S., Mussini, C., Puoti, M., Ammassari, A., Balotta, C., Bandera, A., Bonfanti, P., Borderi, M., Calcagno, A., Calza, L., Capobianchi, M. R., Cingolani, A., Cinque, P., Lichtner, A., Madeddu, G., Maggiolo, F., Marchetti, G., Marcotullio, S., Monno, L., Nozza, S., Quiros Roldan, E., Rossotti, R., Rusconi, S., Santoro, M. M., Saracino, A., Zaccarelli, M., Fanti, I., Galli, L., Lorenzini, P., 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., Santoro, C., Suardi, C., Donati, V., Verucchi, G., Minardi, C., Quirino, T., Abeli, C., Manconi, P. E., Piano, P., Cacopardo, B., Celesia, B., Vecchiet, J., Falasca, K., Sighinolfi, L., Segala, D., Mazzotta, F., Vichi, F., Cassola, G., Viscoli, C., Alessandrini, A., Bobbio, N., 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., Gori, A., Guaraldi, G., Lapadula, G., Abrescia, N., Chirianni, A., Borgia, G., Di Martino, F., Maddaloni, L., Gentile, I., Orlando, R., Cascio, A., Colomba, C., 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., Iaiani, G., Fontanelli Sulekova, L., Cecchetto, M., Viviani, F., Mura, M. S., De Luca, A., Rossetti, B., Caramello, P., Orofino, G. C., Bonora, S., Sciandra, M., Bassetti, M., Londero, A., Pellizzer, G., Manfrin, V., Efficacy and tolerability of switching to a dual therapy with darunavir/ritonavir plus raltegravir in HIV-infected patients with HIV-1 RNA ≤50 cp/mL, <<INFECTION>>, 2017; (n/a): 1-8. [doi:10.1007/s15010-017-1018-z] [http://hdl.handle.net/10807/102547]

Efficacy and tolerability of switching to a dual therapy with darunavir/ritonavir plus raltegravir in HIV-infected patients with HIV-1 RNA ≤50 cp/mL

Di Giambenedetto, Simona;De Luca, Andrea;Cauda, Roberto;Fanti, Iuri;Baldin, Gianmaria;Rossetti, Barbara;
2017

Abstract

Background: Nucleos(t)ide reverse transcriptase inhibitors (NRTI) toxicity may represent a threat for long-term success of combined antiretroviral therapy. Some studies have suggested a possible improvement of NRTI-related toxicity after switching to NRTI-sparing regimens. Objectives: We aimed to explore the efficacy and tolerability of switching to darunavir/ritonavir (DRV/r) plus raltegravir (RAL) while having a viral load (VL) ≤50 copies/mL in the clinical setting. Study design: Treatment-experienced HIV 1-infected patients enrolled in the ICONA Foundation Study cohort were included if they switched their current regimen to DRV/r + RAL with a HIV-RNA ≤50 copies/mL. Different definitions of virological failure (VF) and treatment failure (TF) were employed. Kaplan–Meier curves and Cox regression models were performed to estimate time to event probability. Results: We included 72 HIV-infected patients, 22 (31%) of these were female, 31 (43%) men who have sex with men (MSM) amd 15 (21%) had hepatitis co-infections. Median age was 44 (IQR: 35-50) years amd CD4 count was 389 (IQR 283-606) cells/mmc. Median follow-up time for TF was 24 (IQR 9–31) months. Twenty-five discontinuations occurred (60% simplifications); only 2 (8%) were toxicity-driven (lipid elevations). The probability of VF (confirmed VL >50 copies/mL) was estimated at 7% [95% confidence interval (CI) 1–13%] by 12 and 9% (95% CI 2–16%) by 24 months. When considering TF, we found a probability of stop/intensification/single VL > 200 copies/mL of 13% (95% CI 1–17%) and 22% (95% CI 11–33%) by 12 and 24 months. Female gender (adjusted relative hazard, ARH = 0.10; 95% CI 0.01–0.74; p = 0.024) and older age (AHR = 0.50 per 10 years older; 95% CI 0.25–0.99; p = 0.045) were associated with a lower risk of TF. A previous PI failure was strongly associated with TF (AHR = 52.6, 95% CI 3.6–779; p = 0.004). Conclusions: DRV/r + RAL is a valuable NRTI-sparing option, especially in female and older patients, with a relatively low risk of VF and good tolerability after 2 years since start in an ART-experienced population. However, previous PI-failure should be a limiting factor for this strategy.
Inglese
Madeddu, G., Rusconi, S., Cozzi Lepri, A., Di Giambenedetto, S., Bonora, S., Carbone, A., De Luca, A., Gianotti, N., Di Biagio, A., Antinori, A., D’arminio Monforte, A., Andreoni, M., Angarano, G., Antinori, 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., Cozzi Lepri, A., Girardi, E., Lo Caputo, S., Mussini, C., Puoti, M., Ammassari, A., Balotta, C., Bandera, A., Bonfanti, P., Borderi, M., Calcagno, A., Calza, L., Capobianchi, M. R., Cingolani, A., Cinque, P., Lichtner, A., Madeddu, G., Maggiolo, F., Marchetti, G., Marcotullio, S., Monno, L., Nozza, S., Quiros Roldan, E., Rossotti, R., Rusconi, S., Santoro, M. M., Saracino, A., Zaccarelli, M., Fanti, I., Galli, L., Lorenzini, P., 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., Santoro, C., Suardi, C., Donati, V., Verucchi, G., Minardi, C., Quirino, T., Abeli, C., Manconi, P. E., Piano, P., Cacopardo, B., Celesia, B., Vecchiet, J., Falasca, K., Sighinolfi, L., Segala, D., Mazzotta, F., Vichi, F., Cassola, G., Viscoli, C., Alessandrini, A., Bobbio, N., 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., Gori, A., Guaraldi, G., Lapadula, G., Abrescia, N., Chirianni, A., Borgia, G., Di Martino, F., Maddaloni, L., Gentile, I., Orlando, R., Cascio, A., Colomba, C., 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., Iaiani, G., Fontanelli Sulekova, L., Cecchetto, M., Viviani, F., Mura, M. S., De Luca, A., Rossetti, B., Caramello, P., Orofino, G. C., Bonora, S., Sciandra, M., Bassetti, M., Londero, A., Pellizzer, G., Manfrin, V., Efficacy and tolerability of switching to a dual therapy with darunavir/ritonavir plus raltegravir in HIV-infected patients with HIV-1 RNA ≤50 cp/mL, <<INFECTION>>, 2017; (n/a): 1-8. [doi:10.1007/s15010-017-1018-z] [http://hdl.handle.net/10807/102547]
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