Giordano Madeddu1, Stefano Rusconi2, Alessandro Cozzi-Lepri3, Simona Di Giambenedetto4, Stefano Bonora5, Alessia Carbone6, Andrea De Luca7, Nicola Gianotti6, Antonio Di Biagio8, Andrea Antinori9. 1. Department of Clinical and Experimental Medicine, Unit of Infectious Diseases, University of Sassari, Viale San Pietro 8, 07100, Sassari, Italy. giordano@uniss.it. 2. Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan, Milan, Italy. 3. Department of Infection and Population Health, Division of Population Health, Hampstead Campus, University College London, London, UK. 4. Catholic University of the Sacred Heart, Milan, Unit of Infectious Diseases, Agostino Gemelli Polyclinic Foundation, Rome, Italy. 5. Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Turin, Italy. 6. Infectious Diseases Department, San Raffaele Scientific Institute, Università vita e salute, Milan, Italy. 7. Division of Infectious Diseases, Department of Medical Biotechnologies, University of Siena and Siena University Hospital, Siena, Italy. 8. Unit of Infectious Diseases, IRCCS San Martino Hospital-IST, Genoa, Italy. 9. Clinical Department, National Institute of Infectious Diseases 'Lazzaro Spallanzani', Rome, Italy.
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.
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-infectedpatients 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-infectedpatients, 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.
Authors: Antonio Di Biagio; Elena Ricci; Claudio Viscoli; Alessio Mesini; Barbara Menzaghi; Laura Carenzi; Giancarlo Orofino; Giustino Parruti; Canio Martinelli; Giordano Madeddu; Giuseppe Vittorio De Socio; Marco Franzetti; Tiziana Quirino; Paolo Bonfanti Journal: Curr HIV Res Date: 2013-04 Impact factor: 1.581
Authors: A Mondi; M Fabbiani; N Ciccarelli; M Colafigli; A D'Avino; A Borghetti; R Gagliardini; R Cauda; A De Luca; S Di Giambenedetto Journal: J Antimicrob Chemother Date: 2015-02-26 Impact factor: 5.790
Authors: Adrian Curran; Polyana Monteiro; Pere Domingo; Judit Villar; Arkaitz Imaz; Esteban Martínez; Irene Fernández; Hernando Knobel; Daniel Podzamczer; Jose Antonio Iribarren; María Peñaranda; Manuel Crespo Journal: J Antimicrob Chemother Date: 2014-01-10 Impact factor: 5.790
Authors: Lesley A Inker; Christopher H Schmid; Hocine Tighiouart; John H Eckfeldt; Harold I Feldman; Tom Greene; John W Kusek; Jane Manzi; Frederick Van Lente; Yaping Lucy Zhang; Josef Coresh; Andrew S Levey Journal: N Engl J Med Date: 2012-07-05 Impact factor: 91.245
Authors: Ana Blas-García; Alberto Martí-Rodrigo; Víctor M Víctor; Miriam Polo; Fernando Alegre; Haryes A Funes; Nadezda Apostolova; Juan V Esplugues Journal: J Antimicrob Chemother Date: 2016-01-07 Impact factor: 5.790