TPIO DI
OTTIMIZZAZIONE SCOPI ALTRI POTENZIALI VANTAGGI POTENZIALI SVANTAGGI RACCOMANDAZIONE (FORZA/EVIDENZA) BIBLIOGRAFICI RIFERIMENTI Da ABC a TDF
(a) Per tossicità specifica. Persistente virologica, miglior profilo risposta lipidico.
Maggior numero di eventi avversi e di sospensioni
terapeutiche, incremento
della creatinina; osso non valutato.
[BI] [1-3]
Da TDF ad ABC
(b) Per tossicità specifica. Minor impatto sul turn over osseo. Non valutato impatto su rene, cuore e profilo lipidico; non si può escludere una tossicità cardiovascolare di ABC.
[BII] [4-7]
Da EFV a NVP
(c) Per tossicità specifica. Migliore impatto sui lipidi, migliore penetrazione SNC,
riduzione tossicità
neurologica.
Tossicità cutanea ed epatica nel breve termine, mancanza
di co-formulazione. [BI] [8, 9]
Da ATV/r a ATV (d) Per tossicità specifica. Riduzione iperbilirubinemia, modesta riduzione lipidi, minori effetti collaterali
Più bassa barriera genetica, non indicato con TDF e
anti-acidi. [CI] [10-12]
Da EFV/FTC/TDF a EVG/COBI/FTC/TAF FDC (e)
Per tossicità. Maggiore successo
virologico, minori effetti
collaterali. Riduzione
Lieve peggioramento del profilo lipidico, le cui
proteinuria e miglioramento
BMD. lungo termine saranno da definire.
Da
EVG/COBI/FTC/TDF
FDC a
EVG/COBI/FTC/TAF FDC (f)
Per tossicità. Minori effetti collaterali.
Riduzione proteinuria e miglioramento BMD.
Lieve peggioramento del profilo lipidico, le cui implicazioni cliniche sul lungo termine saranno da definire.
[AI] [13]
(a) = In due RCT sulla semplificazione da ABC a TDF in presenza di una simile risposta virologica si è assistito ad un netto miglioramento del profilo lipidico a fronte di un peggioramento del filtrato glomerulare nei pazienti in terapia con TDF in uno dei 2 RCT. Lo studio SWIFT ha invece evidenziato un minor numero di fallimenti virologici nei pazienti in terapia con TDF, il miglioramento del profilo lipidico e dei fattori di rischio cardiovascolari a fronte del peggioramento della funzione renale in entrambi i gruppi ma in particolare nei pazienti trattati con TDF.
(b) = In un analisi retrospettiva di 225 pazienti adulti canadesi durante la semplificazione da TDF a ABC si è assistito al mantenimento della risposta virologica ed al miglioramento della funzione renale sia in pazienti trattati con atazanavir che con altri farmaci. In tre lavori spagnoli la semplificazione ad ABC ha determinato un minor impatto sul turn over metabolico osseo ed un miglioramento non significativo della densità ossea femorale.
(c) = Un piccolo RCT francese – Sirocco Study – ha dimostrato nello switch da EFV a NVP il miglioramento del profilo lipidico e degli eventi avversi del SNC a fronte della persistente risposta virologica. Uno studio farmacocinetico su 15 pazienti consiglia la semplificazione da EFV a NVP al dosaggio di 200 mg BID già nei primi 14 gg di terapia per raggiungere più rapidamente la concentrazione terapeutica del farmaco. La semplificazione a nevirapina da farmaci con disturbi del SNC (EFV in particolare) in una coorte di 129 pazienti spagnoli in soppressione virologica ha portato a una migliore aderenza alla terapia e qualità di vita.
(d) = Indicato nei pazienti con intolleranza a ritonavir. Non consigliato in caso di co-somministrazione di tenofovir o farmaci anti-acidi. In questo caso, se è necessario per tossicità sospendere il ritonavir, la concentrazione plasmatica di atazanavir deve essere periodicamente verificata mediante TDM (vedi sezione specifica). (e) = Lo studio GS-109 ha evidenziato in 376 pazienti randomizzati la superiorità dello switch in termini di successo virologico alla settimana 48, un miglioramento della mineralizzazione ossea e della funzionalità renale tubulare e un lieve peggioramento del profilo lipidico, le cui implicazioni cliniche sul lungo termine saranno da definire.
(f) = Lo studio GS-109 ha evidenziato in 459 pazienti randomizzati la non-inferiorità dello switch in termini di successo virologico alla settimana 48, un miglioramento della mineralizzazione ossea e della funzionalità renale tubulare e un lieve peggioramento del profilo lipidico, le cui implicazioni cliniche sul lungo termine saranno da definire.
RIFERIMENTI BIBLIOGRAFICI
Riduzione del numero di farmaci antiretrovirali
1. Perez-Molina JA, Rubio R, Rivero A, Pasquau J, Suárez-Lozano I, Riera M, Estébanez M, Santos J, Sanz-Moreno J, Troya J, Mariño A, Antela A, Navarro J,
Esteban H, Moreno S; GESIDA 7011 Study Group. Dual treatment with atazanavir-ritonavir plus lamivudine versus triple treatment with atazanavir-ritonavir plus two nucleos(t)ides in virologically stable patients with HIV-1 (SALT): 48 week results from a randomised, open-label, non-inferiority trial. Lancet Infect Dis. 2015 Jul;15(7):775-84. doi: 10.1016/S1473-3099(15)00097-3.
2. Arribas JR, Girard PM, Landman R, Pich J, Mallolas J, Martínez-Rebollar M, Zamora FX, Estrada V, Crespo M, Podzamczer D, Portilla J, Dronda F, Iribarren JA, Domingo P, Pulido F, Montero M, Knobel H, Cabié A, Weiss L, Gatell JM; OLE/RIS-EST13 Study Group. Dual treatment with lopinavir-ritonavir plus lamivudine versus triple treatment with lopinavir-ritonavir plus lamivudine or emtricitabine and a second nucleos(t)ide reverse transcriptase inhibitor for maintenance of HIV-1 viral suppression (OLE): a randomised, open-label, non-inferiority trial. Lancet Infect Dis. 2015 Jul;15(7):785-92. doi: 10.1016/S1473-3099(15)00096-1.
3. Negredo E, Moltó J, Burger D, Côté H, Miró O, Ribalta J, Martínez E, Puig J, Ruiz L, Salazar J, López S,Montaner J, Rey-Joly C, Clotet B. Lopinavir/ritonavir plus nevirapine as a nucleoside-sparing approach in antiretroviral experienced patients (NEKA study). J AIDS 2005;38:47-52.
4. Negredo E, Miró O, Rodríguez-Santiago B, Garrabou G, Estany C, Masabeu A, Force L, Barrufet P, Cucurull J, Domingo P, Alonso-Villaverde C, Bonjoch A,
Morén C, Pérez-Alvarez N, Clotet B; MULTINEKA Study Group. Improvement of mitochondrial toxicity in patients receiving a nucleoside reverse-transcriptase inhibitor-sparing strategy: results from the Multicenter Study with Nevirapine and Kaletra (MULTINEKA). Clin Infect Dis. 2009 Sep 15;49(6):892-900.
5. Maggiolo F, Valenti D, Callegaro A, Di Filippo E, Gregis G, Rizzi M. Switch from PI/rtv +2 nucleos(t)ides to RPV+DRV/rtv maintains HIV suppression and is well tolerated. 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Vancouver, Canada, 19-22 July 2015. Abs TUPEB270.
6. Ofotokun I, Sheth AN, Sanford SE, Easley KA, Shenvi N, White K, Eaton ME, Del Rio C, Lennox JL. A Switch in Therapy to a Reverse Transcriptase Inhibitor Sparing Combination of Lopinavir/Ritonavir and Raltegravir in Virologically Suppressed HIV-Infected Patients: A Pilot Randomized Trial to Assess Efficacy and Safety Profile: The KITE Study. AIDS Res Hum Retroviruses. 2012 Apr 20.
7. Madeddu G, Rusconi S, Cozzi-Lepri A, Di Giambenedetto S, Bonora S, Carbone A, De Luca A, Gianotti N, Di Biagio A, Antinori A for the Icona Foundation
Study Group. Efficacy and tolerability of switching to a dual therapy with darunavir/r+raltegravir in HIV-infected patients with HIV-1 RNA ≤50 cp/mL. VI Conferenza ICAR 2014, abs OC 7.
8. Nishijima T, Gatanaga H, Shimbo T, Komatsu H, Endo T, Horiba M, Koga M, Naito T, Itoda I, Tei M, Fujii T, Takada K, Yamamoto M, Miyakawa T, Tanabe Y,
Mitsuya H, Oka S; SPARE study team. Switching tenofovir/emtricitabine plus lopinavir/r to raltegravir plus Darunavir/r in patients with suppressed viral load did not result in improvement of renal function but could sustain viral suppression: a randomized multicenter trial. PLoS One. 2013 Aug 8;8(8):e73639. doi: 10.1371/journal.pone.0073639.
9. Di Giambenedetto S, Fabbiani M, Colafigli M, Ciccarelli N, Farina S, Sidella L, D'Avino A, Mondi A, Cingolani A, Tamburrini E, Murri R, Navarra P, Cauda R, De Luca A Safety and feasibility of treatment simplification to atazanavir/ritonavir + lamivudine in HIV-infected patients on stable treatment with two nucleos(t)ide reverse transcriptase inhibitors + atazanavir/ritonavir with virological suppression (Atazanavir and Lamivudine for treatment Simplification, AtLaS pilot study). J Antimicrob Chemother. 2013 Jun;68(6):1364-7
10. Gianotti N, Poli A, Galli L, Maillard M, Bossolasco S, Spagnuolo V, Nozza S, Guffanti M, Gaiera G, Cernuschi M, Lazzarin A, Castagna A. Dual regimen with darunavir/ritonavir 800/100 mg QD and either lamivudine or emtricitabine as maintenance therapy in HIV-infected patients with HIV-RNA <50 copies/mL. VI Conferenza ICAR 2014, abs OC 5.
11. Borghetti A, Fabbiani M, Piccoli B, Mondi A, D’Avino A, Gagliardini R, Lamonica S, Ciccarelli N, Fanti I, Cauda R, De Luca A, Di Giambenedetto S. Simplification therapy with lamivudine and boosted darunavir in a cohort of treatment-experienced HIV-infected patients. VI Conferenza ICAR 2014, abs OC 6. 12. Di Giambenedetto S, Fabbiani M, Quiros Roldan E, Latini A, D’Ettorre G, Antinori A, Castagna A, Orofino G, Francisci D, Chinello P, Madeddu G, Grima P,
Rusconi S, Del Pin B, Mondi A, Borghetti A, Castelli F, Colafigli M, De Luca A, Cauda R. Simplification to Atazanavir/ritonavir+Lamivudine versus maintaining atazanavir/ritonavir+2NRTIs in virologically suppressed HIV-infected patients: 48-weeks data of the ATLAS-M Trial. 15th European AIDS Conference, October 21-24, 2015, Barcelona, Spain. Abstract #BPD1/6.
13. Van Lunzen J, Pozniak A, Gatell J, Antinori A, Klauck I, Serrano O, Baakili A, Yu M, Girard PM. HARNESS study: ritonavir-boosted atazanavir (ATV/r)+raltegravir (RAL) switch study in virologically suppressed, HIV-1-infected patients. 20th IAC, Melbourne, 2014. Poster #LBPE19
14. Paton NI, Stöhr W, Arenas-Pinto A, Fisher M, Williams I, Johnson M, Orkin C, Chen F, Lee V, Winston A, Gompels M, Fox J, Scott K, Dunn DT, for the Protease Inhibitor Monotherapy Versus Ongoing Triple Therapy (PIVOT) Trial Team. Protease inhibitor monotherapy for long-term management of HIV infection: a randomised, controlled, open-label, non-inferiority trial. Lancet HIV 2015; doi:10.1016/S2352-3018(15)00176-9.
16. Arribas J , Girard PM , Paton N , Winston A , Marcelin AG , Elbirt D , Hill A , Hadacek MB. Efficacy of PI monotherapy versus triple therapy for 1964 patients in 10 randomised trials. J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19788. doi:10.7448/IAS.17.4.19788. eCollection 2014.
17. Spagnuolo V, Galli L, Bigoloni A, Nozza S, d’Arminio Monforte A, Antinori A, Di Biagio A, Rusconi S, Guaraldi G, Di Giambenedetto S, Lazzarin A, Castagna A. Atazanavir/ritonavir monotherapy as maintenance strategy in HIV-1 treated subjects with viral suppression: 96-week analysis results of the MODAT study. Journal of the International AIDS Society 2014, 17(Suppl 3):19806. http://dx.doi.org/10.7448/IAS.17.4.19806
18. Pulido F, Pérez-Valero I, Delgado R, Arranz A, Pasquau J, Portilla J, Rubio R, González-García J, Miralles P, Pérez-Elías MJ, Ocampo A, Hernando A, Estrada V, Clotet B, Podzamczer D, Arribas JR. Risk factors for loss of virological suppression in patients receiving lopinavir/ritonavir monotherapy for maintenance of HIV suppression. Antivir Ther. 2009;14(2):195-201.
19. Gutmann C, Cusini A, Günthard HF, Fux C, Hirschel B, Decosterd LA, Cavassini M, Yerly S, Vernazza PL; Swiss HIV Cohort Study (SHCS). Randomized controlled study demonstrating failure of LPV/r monotherapy in HIV: the role of compartment and CD4-nadir. AIDS. 2010 Sep 24;24(15):2347-54. doi: 10.1097/QAD.0b013e32833db9a1.
20. Antinori A, Clarke A, Svedhem-Johansson V, Arribas JR, Arenas-Pinto A, Fehr J, Gerstoft J, Horban A, Clotet B, Ripamonti D, Girard PM, Hill AM, Moecklinghoff C. Week 48 efficacy and central nervous system analysis of darunavir/ritonavir monotherapy versus darunavir/ritonavir with two nucleoside analogues. AIDS. 2015;29(14):1811-20.
21. Arribas JR, Clumeck N, Nelson M, Hill A, van Delft Y, Moecklinghoff C. The MONET trial: week 144 analysis of the efficacy of darunavir/ritonavir (DRV/r) monotherapy versus DRV/r plus two nucleoside reverse transcriptase inhibitors, for patients with viral load < 50 HIV-1 RNA copies/mL at baseline. HIV Med. 2012 Aug;13(7):398-405.
22. Valantin MA, Lambert-Niclot S, Flandre P, Morand-Joubert L, Cabiè A, Meynard JL, Ponscarme D, Ajana F, Slama L, Curjol A, Cuzin L, Schneider L, Taburet AM, Marcelin AG, Katlama C; MONOI ANRS 136 Study Group. Long-term efficacy of darunavir/ritonavir monotherapy in patients with HIV-1 viral suppression: week 96 results from the MONOI ANRS 136 study. J Antimicrob Chemother. 2012 Mar;67(3):691-5.
23. Pinnetti C, Lorenzini P, Cozzi-Lepri A, Ottou S, Tommasi C, Zaccarelli M, Perno CF, Capobianchi MR, Girardi E, Antinori A, Ammassari A. Randomized trial of DRV/r or LPV/r QD monotherapy vs maintaining a PI/r-based antiretroviral regimen in persons with suppressed HIV replication. Journal of the International AIDS Society 2014, 17(Suppl 3):19809. http://dx.doi.org/10.7448/IAS.17.4.19809
24. Geretti AM, Arribas JR, Lathouwers E, Foster GM, Yakoob R, Kinloch S, Hill A, van Delft Y, Moecklinghoff C. Dynamics of cellular HIV-1 DNA levels over 144 weeks of darunavir/ritonavir monotherapy versus triple therapy in the MONET trial. HIV Clin Trials. 2013 Jan-Feb;14(1):45-50.
25. Ferretti F, Bigoloni A, Longo V, Galli L, Passeri L, Gerevini S, Spagnuolo V, Lazzarin A, Cinque P, Castagna A. Cerebrospinal fluid markers in long-term atazanavir/ritonavir monotherapy. Conference on Retroviruses and Opportunistic Infections (CROI) 2015; Seattle, Washington. Abs 443.
26. Arribas JR, Delgado R, Arranz A, Muñoz R, Portilla J, Pasquau J, Pérez-Elias MJ, Iribarren JA, Rubio R, Ocampo A, Sánchez-Conde M, Knobel H, Arazo P, Sanz J, López-Aldeguer J, Montes ML, Pulido F; OK04 Study Group. Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and 2 nucleosides for maintenance therapy of HIV: 96-week analysis. J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):147-52.
27. Cameron DW, da Silva BA, Arribas JR, Myers RA, Bellos NC, Gilmore N, King MS, Bernstein BM, Brun SC, Hanna GJ. A 96-week comparison of lopinavir-ritonavir combination therapy followed by lopinavir-lopinavir-ritonavir monotherapy versus efavirenz combination therapy. J Infect Dis. 2008 Jul 15;198(2):234-40. 28. Bierman WF, van Agtmael MA, Nijhuis M, Danner SA, Boucher CA. HIV monotherapy with ritonavir-boosted protease inhibitors: a systematic review. AIDS.
2009 Jan 28;23(3):279-91.
29. D’Arminio Monforte A, Gianotti N, Cozzi-Lepri A, Pinnetti C, Andreoni M, Di Perri G, Galli M, Poli A, Costantini A, Orofino G, Maggiolo F, Mazzarello G, Celesia B, Luciani F, Lazzarin A, Rizzardini G, Bonfanti P, Perno CF, Antinori A. Durability of lopinavi/ritonavir mono-therapy in individuals with viral load ≤ 50 copies/mL in the observational setting. Antiv Ther 2014;19(3):319-24. doi: 10.3851/IMP2687.
30. Cahn P, Montaner J, Junod P, Patterson P, Krolewiecki A, Andrade-Villanueva J, Cassetti I, Sierra-Madero J, Casiró AD, Bortolozzi R, Lupo SH, Longo N,Rampakakis E, Ackad N, Sampalis JS. Pilot, Randomized Study Assessing Safety, Tolerability and Efficacy of Simplified LPV/r Maintenance Therapy in HIV Patients on the 1st PI-Based Regimen. PLoS ONE 6(8): e23726. doi:10.1371/journal.pone.0023726.
31. Cameron DW, da Silva BA, Arribas JR, Myers RA, Bellos NC, Gilmore N, King MS, Bernstein BM, Brun SC, Hanna GJ. A 96-week comparison of lopinavir-ritonavir combination therapy followed by lopinavir-lopinavir-ritonavir monotherapy versus efavirenz combination therapy. J Infect Dis. 2008 Jul 15;198(2):234-240. 32. Gianotti N, Poli A, Galli M, Pan A, Rizzardini G, Soria A, Viale P, Di Biagio A, Quirino T, Viganò P, Bonfanti P, d'Arminio Monforte A, Fortino I, Lazzarin A.
Monotherapy with lopinavir/ritonavir versus standard of care in HIV-infected patients virologically suppressed while on treatment with a protease inhibitor-based regimens: results from the MoLo Study. New Microbiol 2014 (in stampa).
33. Swindells S, DiRienzo AG, Wilkin T, Fletcher CV, Margolis DM, Thal GD, Godfrey C, Bastow B, Ray MG, Wang H, Coombs RW, McKinnon J, Mellors JW; AIDS Clinical Trials Group 5201 Study Team. Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression. JAMA. 2006 Aug 16;296(7):806-14.
34. Karlström O, Josephson F, Sönnerborg A. Early virologic rebound in a pilot trial of ritonavir-boosted atazanavir as maintenance monotherapy. J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):417-22.
Riduzione del numero di dosi/somministrazioni e di compresse giornaliere
1. Mora-Peris B, Watson V, Vera JH, Weston R, Waldman AD, Kaye S, Khoo S, Mackie NE, Back D, Winston A. Rilpivirine exposure in plasma and sanctuary site
compartments after switching from nevirapine-containing combined antiretroviral therapy. J Antimicrob Chemother. 2014 Jun;69(6):1642-7. doi: 10.1093/jac/dku018.
2. Allavena C, Dailly E, Reliquet V, Bonnet B, Pineau S, André-Garnier E, Boutoille D, Bouquié R, Raveleau A, Bouchez S, Billaud E, Raffi F. Switching from tenofovir/emtricitabine and nevirapine to a tenofovir/emtricitabine/rilpivirine single-tablet regimen in virologically suppressed, HIV-1-infected subjects. J Antimicrob Chemother. J Antimicrob Chemother. 2014 Oct;69(10):2804-8. doi: 10.1093/jac/dku187.
3. Gianotti N, Poli A, Nozza S, Spagnuolo V, Tambussi G, Bossolasco S, Cinque P, Maillard M, Cernuschi M, Galli L, Lazzarin A, Castagna A. Efficacy and safety in clinical practice of a rilpivirine, tenofovir and emtricitabine single-tablet regimen in virologically suppressed HIV-positive patients on stable antiretroviral therapy. J Int AIDS Soc. 2015 Jul 30;18(1):20037. doi: 10.7448/IAS.18.1.20037.
4. Mills AM, Cohen C, Dejesus E, Brinson C, Williams S, Yale KL, Ramanathan S, Wang MH, White K, Chuck SK, Cheng AK. Efficacy and safety 48 weeks after
switching from efavirenz to rilpivirine using emtricitabine/tenofovir disoproxil fumarate-based single-tablet regimens. HIV Clin Trials. 2013 Sep-Oct;14(5):216-23. doi: 10.1310/hct1405-216.
5. Cazanave C, Reigadas S, Mazubert C, Bellecave P, Hessamfar M, Le Marec F, Lazaro E, Peytavin G, Bruyand M, Fleury H, Dabis F, Neau D.Switch to Rilpivirine/Emtricitabine/Tenofovir Single-Tablet Regimen of Human Immunodeficiency Virus-1 RNA-Suppressed Patients, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales CO3 Aquitaine Cohort, 2012-2014. Open Forum Infect Dis. 2015 Mar 12;2(1)
6. Pozniak A, Markowitz M, Mills A, Stellbrink HJ, Antela A, Domingo P, Girard PM, Henry K, Nguyen T, Piontkowsky D, Garner W, White K, Guyer B. Switching to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of non-nucleoside reverse transcriptase inhibitor with emtricitabine and tenofovir in virologically suppressed adults with HIV (STRATEGY-NNRTI): 48 week results of a randomised, open-label, phase 3b non-inferiority trial. Lancet Infect Dis. 2014 Jul;14(7):590-9. doi: 10.1016/S1473-3099(14)70796-0.
7. Mills A, Garner W, Pozniak A, Berenguer J, Speck RM, Bender R, Nguyen T. Patient-Reported Symptoms Over 48 Weeks in a Randomized, Open-Label,
Phase IIIb Non-Inferiority Trial of Adults with HIV Switching to Co-Formulated Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir DF versus Continuation of Non-Nucleoside Reverse Transcriptase Inhibitor with Emtricitabine and Tenofovir DF. Patient. 2015;8(4):359-71. doi: 10.1007/s40271-015-0129-9
8. Dejesus E, Young B, Morales-Ramirez JO, Sloan L, Ward DJ, Flaherty JF, Ebrahimi R, Maa JF, Reilly K, Ecker J, McColl D, Seekins D, Farajallah A; AI266073 Study Group. Simplification of antiretroviral therapy to a single-tablet regimen consisting of efavirenz, emtricitabine, and tenofovir disoproxil fumarate versus unmodified antiretroviral therapy in virologically suppressed HIV-1-infected patients. J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):163-74.
9. Martínez E, Arnaiz JA, Podzamczer D, Dalmau D, Ribera E, Domingo P, Knobel H, Leyes M, Pedrol E, Force L, de Lazzari E, Gatell JM. Three-year follow-up of protease inhibitor-based regimen simplification in HIV-infected patients. AIDS. 2007 Jan 30;21(3):367-9.
10. Llibre JM, Bravo I, Ornelas A, Santos JR, Puig J, Martin-Iguacel R, Paredes R, Clotet B. Effectiveness of a Treatment Switch to Nevirapine plus Tenofovir and Emtricitabine (or Lamivudine) in Adults with HIV-1 Suppressed Viremia. PLoS One. 2015 Jun 24;10(6):e0128131.
11. Palella FJ Jr, Fisher M, Tebas P, Gazzard B, Ruane P, Van Lunzen J, Shamblaw D, Flamm J, Ebrahimi R, Porter D, White K, Hindman J, Elbert E, De-Oertel S, Fralich T. Simplification to rilpivirine/emtricitabine/tenofovir disoproxil fumarate from ritonavir-boosted protease inhibitor antiretroviral therapy in a randomized trial of HIV-1 RNA-suppressed participants. AIDS. 2014 Jan 28;28(3):335-44. doi: 10.1097/QAD.0000000000000087.
12. Eron JJ, Young B, Cooper DA, Youle M, Dejesus E, Andrade-Villanueva J, Workman C, Zajdenverg R, Fatkenheuer G, Berger DS, Kumar PN, Rodgers AJ, Shaughnessy MA, Walker ML, Barnard RJ, Miller MD, Dinubile MJ, Nguyen BY, Leavitt R, Xu X, Sklar P. Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials. Lancet. 2010 Jan 30;375(9712):396-407. Epub 2010 Jan 12.
13. Martinez E, et al. Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: the SPIRAL study AIDS. 2010 Jul 17;24 (11):1697-707.
14. Curran A, Martinez E, Saumoy M, del Rio L, Crespo M, Larrousse M, Podzamczer D, Burgos J, Lonca M, Domingo P, Gatell JM, Ribera E. Body composition changes after switching from protease inhibitors to raltegravir: SPIRAL-LIP substudy. AIDS. 2012;26:475-81.
15. Arribas JR, Pialoux G, Gathe J, Di Perri G, Reynes J, Tebas P, Nguyen T, Ebrahimi R, White K, Piontkowsky D. Simplification to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of ritonavir-boosted protease inhibitor with emtricitabine and tenofovir in adults with virologically suppressed HIV (STRATEGY-PI): 48 week results of a randomised, open-label, phase 3b, non-inferiority trial. Lancet Infect Dis. 2014 Jul;14(7):581-9. doi: 10.1016/S1473-3099(14)70782-0.
16. Gathe J, Arribas JR, Van Lunzen J, Garner W, Speck RM, Bender R, Shreay S, Nguyen T. Patient-Reported Symptoms over 48 Weeks in a Randomized, Open-Label, Phase 3b Non-inferiority Trial of Adults with HIV Switching to Coformulated Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir DF Versus Continuation of Ritonavir-Boosted Protease Inhibitor with Emtricitabine and Tenofovir DF. Patient. 2015 Aug 1
17. Trottier B, Lake J, Logue L, Brinson C, Santiago L, Brennan C, Koteff J, Wynne B, Granier C, Aboud M. Switching to Abacavir/Dolutegravir/Lamivudine Fixed Dose Combination (ABC/DTG/3TC FDC) from a PI, INI or NNRTI Based Regimen Maintains HIV Suppression. ICAAC 2015 55th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 5-9, 2015, San Diego, CA.
18. Yang SP, Liu WC, Lee KY, Wu BR, Su YC, Wu PY, Zhang JY, Luo YZ, Sun HY, Chang SY, Lin SW, Hung CC. Effectiveness of a reduced dose of efavirenz plus 2 NRTIs as maintenance antiretroviral therapy with the guidance of therapeutic drug monitoring. J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19524. 19. Nicastri E,Bellagamba R, Tommasi C, Gallo AL, Tempestilli M, Angeletti C, Zaccarelli M, Ammassari A, Pinnetti C, Antinori A, Narciso P, Ascoli Marchetti T,
Boumis E, Cerva C, Cicalini S, Corpolongo A, Giancola ML, De Nardo P, Fazio S, Gentilotti E, Liuzzi G, Mencarini P, Pucci L, Sampaolesi A, Stella CM, Viscione M. Randomized clinical trial comparing the safety and efficacy of the use of fixed-dose combination efavirenz/tenofovir/emtricitabine on alternate days versus continuous treatment. VII ICAR 2015, OC 62.
20. Gatell J, Salmon-Ceron D, Lazzarin A, Van Wijngaerden E, Antunes F, Leen C, Horban A, Wirtz V, Odeshoo L, Van den Dungen M, Gruber C, Ledesma E; SWAN Study Group. Efficacy and safety of atazanavir-based highly active antiretroviral therapy in patients with virologic suppression switched from a stable, boosted or unboosted protease inhibitor treatment regimen: the SWAN Study (AI424-097) 48-week results. Clin Infect Dis. 2007 Jun 1;44(11):1484-92. Epub 2007 Apr 25.
21. Mallolas J, Podzamczer D, Milinkovic A, Domingo P, Clotet B, Ribera E, Gutiérrez F, Knobel H, Cosin J, Ferrer E, Arranz JA, Roca V, Vidal F, Murillas J, Pich J, Pedrol E, Llibre JM, Dalmau D, García I, Aranda M, Cruceta A, Martínez E, Blanco JL, Lazzari E, Gatell JM; ATAZIP Study Group. Efficacy and safety of switching from boosted lopinavir to boosted atazanavir in patients with virological suppression receiving a LPV/r-containing HAART: the ATAZIP study. J Acquir Immune Defic Syndr. 2009 May 1;51(1):29-36.
22. Ucciferri C, Falasca K, Vignale F, Di Nicola M, Pizzigallo E, Vecchiet J. Improved metabolic profile after switch to darunavir/ritonavir in HIV positive patients previously on protease inhibitor therapy. J Med Virol. 2013; 85(5):755-9.
23. Cahn P, Fourie J, Grinsztejn B, Hodder S, Molina JM, Ruxrungtham K, Workman C, Van De Casteele T, De Doncker P, Lathouwers E, Tomaka F. Week 48 analysis of once-daily vs. twice-daily darunavir/ritonavir in treatment-experienced HIV-1-infected patients. AIDS. 2011 Apr 24;25(7):929-39. doi: 10.1097/QAD.0b013e328345ee95.
24. Mills T, Andrade J, DiPerri G, Van Lunzen J, Koenig E, Elion R, Cavassini M, Valdez Madruga J, Brunetta J, Shamblaw D, DeJesus E, Cohen C, Plummer A, Liu Y, McCallister S. Switching from a tenofovir disoproxil fumarate (TDF)-based regimen to a tenofovir alafenamide (TAF)-based regimen: data in virologically suppressed adults through 48 weeks of treatment. IAS 2015, abs TUAB0102.
Altre strategie di ottimizzazione
1. Campo R, DeJesus E, Bredeek UF SWIFT: prospective 48-week study to evaluate efficacy and safety of switching to emtricitabine/tenofovir from