Long-term effectiveness of unboosted atazanavir plus abacavir/lamivudine in subjects with virological suppression : a prospective cohort study

Llibre, J.M.; Cozzi-Lepri, A.; Pedersen, C.; Ristola, M.; Losso, M.; Mocroft, A.; Mitsura, V.; Falconer, K.; Maltez, F.; Beniowski, M.; Vullo, V.; Hassoun, G.; Kuzovatova, E.; Szlavik, J.; Kuznetsova, A.; Stellbrink, H.-.; Duvivier, C.; Edwards, S.; Laut, K.; Paredes, R.; Losso, M.; Kundro, M.; Vetter, N.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V.M.; Paduto, D.; Clumeck, N.; De Wit, S.; Delforge, M.; Florence, E.; Vandekerckhove, L.; Hadziosmanovic, V.; Kostov, K.; Begovac, J.; Machala, L.; Jilich, D.; Sedlacek, D.; Kronborg, G.; Benfield, T.; Gerstoft, J.; Katzenstein, T.; Moller, N.F.; Pedersen, C.; Ostergaard, L.; Dragsted, U.B.; Nielsen, L.N.; Zilmer, K.; Smidt, J.; Ristola, M.; Aho, I.; Viard, J.-.; Girard, P.-.; Cotte, L.; Pradier, C.; Fontas, E.; Dabis, F.; Neau, D.; Duvivier, C.; Rockstroh, J.; Schmidt, R.; Degen, O.; Stellbrink, H.J.; Stefan, C.; Bogner, J.; Fatkenheuer, G.; Chkhartishvili, N.; Kosmidis, J.; Gargalianos, P.; Xylomenos, G.; Lourida, P.; Sambatakou, H.; Szlavik, J.; Gottfredsson, M.; Mulcahy, F.; Yust, I.; Turner, D.; Burke, M.; Shahar, E.; Hassoun, G.; Elinav, H.; Haouzi, M.; Elbirt, D.; Sthoeger, Z.M.; D'Arminio Monforte, A.; Esposito, R.; Mazeu, I.; Mussini, C.; Mazzotta, F.; Gabbuti, A.; Vullo, V.; Lichtner, M.; Zaccarelli, M.; Antinori, A.; Acinapura, R.; Plazzi, M.; Lazzarin, A.; Castagna, A.; Gianotti, N.; Galli, M.; Ridolfo, A.; Rozentale, B.; Uzdaviniene, V.; Matulionyte, R.; Staub, T.; Hemmer, R.; Reiss, P.; Ormaasen, V.; Maeland, A.; Bruun, J.; Knysz, B.; Gasiorowski, J.; Inglot, M.; Horban, A.; Bakowska, E.; Flisiak, R.; Grzeszczuk, A.; Parczewski, M.; Pynka, M.; Maciejewska, K.; Beniowski, M.; Mularska, E.; Smiatacz, T.; Gensing, M.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Mozer-Lisewska, I.; Doroana, M.; Caldeira, L.; Mansinho, K.; Maltez, F.; Radoi, R.; Oprea, C.; Rakhmanova, A.; Rakhmanova, A.; Trofimora, T.; Khromova, I.; Kuzovatova, E.; Jevtovic, D.; Shunnar, A.; Stanekova, D.; Tomazic, J.; Gatell, J.M.; Miro, J.M.; Moreno, S.; Rodriguez, J.M.; Clotet, B.; Jou, A.; Paredes, R.; Tural, C.; Puig, J.; Bravo, I.; Domingo, P.; Gutierrez, M.; Mateo, G.; Sambeat, M.A.; Laporte, J.M.; Falconer, K.; Thalme, A.; Sonnerborg, A.; Blaxhult, A.; Flamholc, L.; Ledergerber, B.; Weber, R.; Cavassini, M.; Calmy, A.; Furrer, H.; Battegay, M.; Schmid, P.; Kravchenko, E.; Frolov, V.; Kutsyna, G.; Baskakov, I.; Kuznetsova, A.; Kyselyova, G.; Sluzhynska, M.; Gazzard, B.; Johnson, A.M.; Simons, E.; Edwards, S.; Phillips, A.; Johnson, M.A.; Mocroft, A.; Orkin, C.; Weber, J.; Scullard, G.; Clarke, A.; Leen, C.; Lundgren, J.; Grarup, J.; Thiebaut, R.; Burger, D.; Peters, L.; Matthews, C.; Fischer, A.H.; Bojesen, A.; Raben, D.; Kristensen, D.; Larsen, J.F.; Podlekareva, D.; Shepherd, L.; Schultze, A.

doi:10.1097/MD.0000000000005020

Effectiveness data of an unboosted atazanavir (ATV) with abacavir/lamivudine (ABC/3TC) switch strategy in clinical routine are scant. We evaluated treatment outcomes of ATV + ABC/3TC in pretreated subjects in the EuroSIDA cohort when started with undetectable plasma HIV-1 viral load (pVL), performing a time to loss of virological response (TLOVR <50copies/mL) and a snapshot analysis at 48, 96, and 144 weeks. Virological failure (VF) was defined as confirmed pVL >50copies/mL. We included 285 subjects, 67% male, with median baseline CD4 530 cells, and 44 months with pVL ≤50copies/mL. The third drug in the previous regimen was ritonavir-boosted atazanavir (ATV/r) in 79 (28%), and another ritonavir-boosted protease inhibitor (PI/r) in 29 (10%). Ninety (32%) had previously failed with a PI. Proportions of people with virological success at 48/96/144 weeks were 90%/87%/88% (TLOVR) and 74%/67%/59% (snapshot analysis), respectively. The rates of VF were 8%/8%/6%. Rates of adverse events leading to study discontinuation were 0.4%/1%/2%. The multivariable adjusted analysis showed an association between VF and nadir CD4+ (hazard ratio [HR] 0.63 [95% confidence interval [CI]: 0.42-0.93] per 100 cells higher), time with pVL ≤50copies/mL (HR 0.87 [95% CI: 0.79-0.96] per 6 months longer), and previous failure with a PI (HR 2.78 [95% CI: 1.28-6.04]). Resistance selection at failure was uncommon. A switch to ATV + ABC/3TC in selected subjects with suppressed viremia was associated with low rates of VF and discontinuation due to adverse events, even in subjects not receiving ATV/r. The strategy might be considered in those with long-term suppression and no prior PI failure.

Long-term effectiveness of unboosted atazanavir plus abacavir/lamivudine in subjects with virological suppression : a prospective cohort study / J.M. Llibre, A. Cozzi-Lepri, C. Pedersen, M. Ristola, M. Losso, A. Mocroft, V. Mitsura, K. Falconer, F. Maltez, M. Beniowski, V. Vullo, G. Hassoun, E. Kuzovatova, J. Szlavik, A. Kuznetsova, H.-. Stellbrink, C. Duvivier, S. Edwards, K. Laut, R. Paredes, M. Losso, M. Kundro, N. Vetter, R. Zangerle, I. Karpov, A. Vassilenko, V.M. Mitsura, D. Paduto, N. Clumeck, S. De Wit, M. Delforge, E. Florence, L. Vandekerckhove, V. Hadziosmanovic, K. Kostov, J. Begovac, L. Machala, D. Jilich, D. Sedlacek, G. Kronborg, T. Benfield, J. Gerstoft, T. Katzenstein, N.F. Moller, C. Pedersen, L. Ostergaard, U.B. Dragsted, L.N. Nielsen, K. Zilmer, J. Smidt, M. Ristola, I. Aho, J.-. Viard, P.-. Girard, L. Cotte, C. Pradier, E. Fontas, F. Dabis, D. Neau, C. Duvivier, J. Rockstroh, R. Schmidt, O. Degen, H.J. Stellbrink, C. Stefan, J. Bogner, G. Fatkenheuer, N. Chkhartishvili, J. Kosmidis, P. Gargalianos, G. Xylomenos, P. Lourida, H. Sambatakou, J. Szlavik, M. Gottfredsson, F. Mulcahy, I. Yust, D. Turner, M. Burke, E. Shahar, G. Hassoun, H. Elinav, M. Haouzi, D. Elbirt, Z.M. Sthoeger, A. D'Arminio Monforte, R. Esposito, I. Mazeu, C. Mussini, F. Mazzotta, A. Gabbuti, V. Vullo, M. Lichtner, M. Zaccarelli, A. Antinori, R. Acinapura, M. Plazzi, A. Lazzarin, A. Castagna, N. Gianotti, M. Galli, A. Ridolfo, B. Rozentale, V. Uzdaviniene, R. Matulionyte, T. Staub, R. Hemmer, P. Reiss, V. Ormaasen, A. Maeland, J. Bruun, B. Knysz, J. Gasiorowski, M. Inglot, A. Horban, E. Bakowska, R. Flisiak, A. Grzeszczuk, M. Parczewski, M. Pynka, K. Maciejewska, M. Beniowski, E. Mularska, T. Smiatacz, M. Gensing, E. Jablonowska, E. Malolepsza, K. Wojcik, I. Mozer-Lisewska, M. Doroana, L. Caldeira, K. Mansinho, F. Maltez, R. Radoi, C. Oprea, A. Rakhmanova, A. Rakhmanova, T. Trofimora, I. Khromova, E. Kuzovatova, D. Jevtovic, A. Shunnar, D. Stanekova, J. Tomazic, J.M. Gatell, J.M. Miro, S. Moreno, J.M. Rodriguez, B. Clotet, A. Jou, R. Paredes, C. Tural, J. Puig, I. Bravo, P. Domingo, M. Gutierrez, G. Mateo, M.A. Sambeat, J.M. Laporte, K. Falconer, A. Thalme, A. Sonnerborg, A. Blaxhult, L. Flamholc, B. Ledergerber, R. Weber, M. Cavassini, A. Calmy, H. Furrer, M. Battegay, P. Schmid, E. Kravchenko, V. Frolov, G. Kutsyna, I. Baskakov, A. Kuznetsova, G. Kyselyova, M. Sluzhynska, B. Gazzard, A.M. Johnson, E. Simons, S. Edwards, A. Phillips, M.A. Johnson, A. Mocroft, C. Orkin, J. Weber, G. Scullard, A. Clarke, C. Leen, J. Lundgren, J. Grarup, R. Thiebaut, D. Burger, L. Peters, C. Matthews, A.H. Fischer, A. Bojesen, D. Raben, D. Kristensen, J.F. Larsen, D. Podlekareva, L. Shepherd, A. Schultze. - In: MEDICINE. - ISSN 0025-7974. - 95:40(2016 Oct), pp. e5020.1-e5020.7. [10.1097/MD.0000000000005020]

Long-term effectiveness of unboosted atazanavir plus abacavir/lamivudine in subjects with virological suppression : a prospective cohort study

Llibre J. M.;Cozzi-Lepri A.;Pedersen C.;Ristola M.;Losso M.;Mocroft A.;Mitsura V.;Falconer K.;Maltez F.;Beniowski M.;Vullo V.;Hassoun G.;Kuzovatova E.;Szlavik J.;Kuznetsova A.;Stellbrink H. -J.;Duvivier C.;Edwards S.;Laut K.;Paredes R.;Losso M.;Kundro M.;Vetter N.;Zangerle R.;Karpov I.;Vassilenko A.;Mitsura V. M.;Paduto D.;Clumeck N.;De Wit S.;Delforge M.;Florence E.;Vandekerckhove L.;Hadziosmanovic V.;Kostov K.;Begovac J.;Machala L.;Jilich D.;Sedlacek D.;Kronborg G.;Benfield T.;Gerstoft J.;Katzenstein T.;Moller N. F.;Pedersen C.;Ostergaard L.;Dragsted U. B.;Nielsen L. N.;Zilmer K.;Smidt J.;Ristola M.;Aho I.;Viard J. -P.;Girard P. -M.;Cotte L.;Pradier C.;Fontas E.;Dabis F.;Neau D.;Duvivier C.;Rockstroh J.;Schmidt R.;Degen O.;Stellbrink H. J.;Stefan C.;Bogner J.;Fatkenheuer G.;Chkhartishvili N.;Kosmidis J.;Gargalianos P.;Xylomenos G.;Lourida P.;Sambatakou H.;Szlavik J.;Gottfredsson M.;Mulcahy F.;Yust I.;Turner D.;Burke M.;Shahar E.;Hassoun G.;Elinav H.;Haouzi M.;Elbirt D.;Sthoeger Z. M.;A. D'Arminio Monforte;Esposito R.;Mazeu I.;Mussini C.;Mazzotta F.;Gabbuti A.;Vullo V.;Lichtner M.;Zaccarelli M.;Antinori A.;Acinapura R.;Plazzi M.;Lazzarin A.;Castagna A.;Gianotti N.;M. Galli;Ridolfo A.;Rozentale B.;Uzdaviniene V.;Matulionyte R.;Staub T.;Hemmer R.;Reiss P.;Ormaasen V.;Maeland A.;Bruun J.;Knysz B.;Gasiorowski J.;Inglot M.;Horban A.;Bakowska E.;Flisiak R.;Grzeszczuk A.;Parczewski M.;Pynka M.;Maciejewska K.;Beniowski M.;Mularska E.;Smiatacz T.;Gensing M.;Jablonowska E.;Malolepsza E.;Wojcik K.;Mozer-Lisewska I.;Doroana M.;Caldeira L.;Mansinho K.;Maltez F.;Radoi R.;Oprea C.;Rakhmanova A.;Rakhmanova A.;Trofimora T.;Khromova I.;Kuzovatova E.;Jevtovic D.;Shunnar A.;Stanekova D.;Tomazic J.;Gatell J. M.;Miro J. M.;Moreno S.;Rodriguez J. M.;Clotet B.;Jou A.;Paredes R.;Tural C.;Puig J.;Bravo I.;Domingo P.;Gutierrez M.;Mateo G.;Sambeat M. A.;Laporte J. M.;Falconer K.;Thalme A.;Sonnerborg A.;Blaxhult A.;Flamholc L.;Ledergerber B.;Weber R.;Cavassini M.;Calmy A.;Furrer H.;Battegay M.;Schmid P.;Kravchenko E.;Frolov V.;Kutsyna G.;Baskakov I.;Kuznetsova A.;Kyselyova G.;Sluzhynska M.;Gazzard B.;Johnson A. M.;Simons E.;Edwards S.;Phillips A.;Johnson M. A.;Mocroft A.;Orkin C.;Weber J.;Scullard G.;Clarke A.;Leen C.;Lundgren J.;Grarup J.;Thiebaut R.;Burger D.;Peters L.;Matthews C.;Fischer A. H.;Bojesen A.;Raben D.;Kristensen D.;Larsen J. F.;Podlekareva D.;Shepherd L.;Schultze A.

2016

Abstract

Effectiveness data of an unboosted atazanavir (ATV) with abacavir/lamivudine (ABC/3TC) switch strategy in clinical routine are scant. We evaluated treatment outcomes of ATV + ABC/3TC in pretreated subjects in the EuroSIDA cohort when started with undetectable plasma HIV-1 viral load (pVL), performing a time to loss of virological response (TLOVR <50copies/mL) and a snapshot analysis at 48, 96, and 144 weeks. Virological failure (VF) was defined as confirmed pVL >50copies/mL. We included 285 subjects, 67% male, with median baseline CD4 530 cells, and 44 months with pVL ≤50copies/mL. The third drug in the previous regimen was ritonavir-boosted atazanavir (ATV/r) in 79 (28%), and another ritonavir-boosted protease inhibitor (PI/r) in 29 (10%). Ninety (32%) had previously failed with a PI. Proportions of people with virological success at 48/96/144 weeks were 90%/87%/88% (TLOVR) and 74%/67%/59% (snapshot analysis), respectively. The rates of VF were 8%/8%/6%. Rates of adverse events leading to study discontinuation were 0.4%/1%/2%. The multivariable adjusted analysis showed an association between VF and nadir CD4+ (hazard ratio [HR] 0.63 [95% confidence interval [CI]: 0.42-0.93] per 100 cells higher), time with pVL ≤50copies/mL (HR 0.87 [95% CI: 0.79-0.96] per 6 months longer), and previous failure with a PI (HR 2.78 [95% CI: 1.28-6.04]). Resistance selection at failure was uncommon. A switch to ATV + ABC/3TC in selected subjects with suppressed viremia was associated with low rates of VF and discontinuation due to adverse events, even in subjects not receiving ATV/r. The strategy might be considered in those with long-term suppression and no prior PI failure.

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	Parole chiave
	
			Atazanavir; HIV-1; Protease inhibitors: abacavir; Simplification antiretroviral therapy; Adult; Age Factors; Anti-HIV Agents; Atazanavir Sulfate; Dideoxynucleosides; Drug Combinations; Drug Therapy, Combination; Female; HIV Protease Inhibitors; HIV-1; Humans; Lamivudine; Male; Middle Aged; Prospective Studies; Ritonavir; Sex Factors; Viral Load
		
	Settori scientifico-disciplinari dell'articolo
	
			Settore MED/17 - Malattie Infettive
		
	Data di pubblicazione
	
			ott-2016
		
	Rivista in ANCE
	
			MEDICINE
		
	DOI
	
			https://dx.doi.org/10.1097/MD.0000000000005020
		
	Tipologia
	
			Article (author)
		
	Appare nelle tipologie:
	
			01 - Articolo su periodico

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