Changing utilization of Stavudine (d4T) in HIV-positive people in 2006-2013 in the EuroSIDA study

Podlekareva, D.; Grint, D.; Karpov, I.; Vassilenko, A.; Rakmanova, A.; Mansinho, K.; Chentsova, N.; Kravchenko, E.; Zeltina, I.; Losso, M.; Parczewski, M.; Lundgren, J.; Mocroft, A.; Kirk, O.; Losso, M.; Kundro, M.; Vetter, N.; Zangerle, R.; Mitsura, V.M.; Suetnov, O.; Clumeck, N.; De Wit, S.; Delforge, M.; Florence, E.; Vandekerckhove, L.; Hadziosmanovic, V.; Kostov, K.; Begovac, J.; Machala, L.; Jilich, D.; Sedlacek, D.; Nielsen, J.; Kronborg, G.; Benfield, T.; Larsen, M.; Gerstoft, J.; Katzenstein, T.; Hansen, A.-.E.; Skinhoj, P.; Pedersen, C.; Ostergaard, L.; Dragsted, U.B.; Nielsen, L.N.; Zilmer, K.; Smidt, J.; Ristola, M.; Katlama, C.; Viard, J.-.; Girard, P.-.; Vanhems, P.; Pradier, C.; Dabis, F.; Neau, D.; Duvivier, C.; Rockstroh, J.; Schmidt,; van Lunzen, J.; Degen, O.; Stellbrink, H.J.; Bickel, M.; Goethe, J.W.; Bogner, J.; Fatkenheuer, G.; Kosmidis, J.; Gargalianos, P.; Xylomenos, G.; Perdios, J.; Sambatakou, H.; Banhegyi, D.; Gottfredsson, M.; Mulcahy, F.; Yust, I.; Turner, D.; Burke, M.; Pollack, S.; Hassoun, G.; Elinav, H.; Haouzi, M.; D'Arminio Monforte, A.; Esposito, R.; Mazeu, I.; Mussini, C.; Arici, C.; Pristera, R.; Mazzotta, F.; Gabbuti, A.; Vullo, V.; Lichtner, M.; Chirianni, A.; Montesarchio, E.; Gargiulo, M.; D'Offizi, G.; Taibi, C.; Antinori, A.; Lazzarin, A.; Castagna, A.; Gianotti, N.; Galli, M.; Ridolfo, A.; Rozentale, B.; Zeltina, I.; Chaplinskas, S.; Staub, T.; Hemmer, R.; Reiss, P.; Ormaasen, V.; Maeland, A.; Bruun, J.; Knysz, B.; Gasiorowski, J.; Horban, A.; Bakowska, E.; Grzeszczuk, A.; Flisiak, R.; Boron-Kaczmarska, A.; Pynka, M.; Parczewski, M.; Beniowski, M.; Mularska, E.; Trocha, H.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Doroana, M.; Doroana, M.; Caldeira, L.; Maltez, F.; Duiculescu, D.; Rakhmanova, A.; Buzunova, S.; Khromova, I.; Kuzovatova, E.; Jevtovic, D.; Mokras, M.; Stanekova, D.; Tomazic, J.; Gonzalez-Lahoz, J.; Soriano, V.; Labarga, P.; Moreno, S.; Rodriguez, J.M.; Clotet, B.; Jou, A.; Paredes, R.; Tural, C.; Puig, J.; Bravo, I.; Gatell, J.M.; Miro, J.M.; Domingo, P.; Gutierrez, M.; Mateo, G.; Sambeat, M.A.; Medrano, J.; Blaxhult, A.; Flamholc, L.; Thalme, A.; Sonnerborg, A.; Ledergerber, B.; Weber, R.; Francioli, P.; Cavassini, M.; Hirschel, B.; Boffi, E.; Furrer, H.; Battegay, M.; Elzi, L.; Vernazza, P.; Frolov, V.; Kutsyna, G.; Servitskiy, S.; Kuznetsova, A.; Kyselyova, G.; Gazzard, B.; Johnson, A.M.; Simons, E.; Phillips, A.; Johnson, M.A.; Mocroft, A.; Orkin, C.; Weber, J.; Scullard, G.; Fisher, M.; Leen, C.

doi:10.1111/hiv.12254

Objectives: The long-term side effects of stavudine (d4T) led to recommendations in 2009 to phase out use of this drug. We aimed to describe temporal patterns of d4T use across Europe. Methods: Patients taking combination antiretroviral therapy (cART) in EuroSIDA with follow-up after 1 January 2006 were included in the study. cART was defined as d4T-containing [d4T plus at least two other antiretrovirals (ARVs) from any class] or non-d4T-containing (at least three ARVs from any class, excluding d4T). Poisson regression was used to describe temporal changes in the prevalence of d4T use and factors associated with initiating d4T. Results: A total of 5850 patients receiving cART on 1 January 2006 were included in the current analysis, rising to 7768 patients on January 1 2013. During this time, the prevalence of d4T use fell from 11.2% to 0.7%, with an overall decline of 19% per 6 months [95% confidence interval (CI) 19-20%]. d4T use declined fastest in Northern Europe [26% (95% CI 23-29%) per 6 months], and slowest in Eastern Europe [17% (95% CI 16-19%) per 6 months]. In multivariable Poisson regression models, new d4T initiations decreased by 14% per 6 months [adjusted incidence rate ratio (aIRR) 0.86; 95% CI 0.80-0.91]. Factors associated with initiating d4T were residence in Eastern Europe (aIRR 4.31; 95% CI 2.17-9.98) versus other European regions and HIV RNA>400 copies/mL (aIRR 3.11; 95% CI 1.60-6.02) versus HIV RNA<400 copies/mL. Conclusions: d4T use has declined sharply since 2006 to low levels in most regions; however, a low but persistent level of d4T use remains in Eastern Europe, where new d4T initiations post 2006 are also more common. The reasons for the regional differences may be multifactorial, but it is important to ensure that all clinicians treating HIV-positive patients are aware of the potential harmful effects associated with d4T.

Changing utilization of Stavudine (d4T) in HIV-positive people in 2006-2013 in the EuroSIDA study / D. Podlekareva, D. Grint, I. Karpov, A. Vassilenko, A. Rakmanova, K. Mansinho, N. Chentsova, E. Kravchenko, I. Zeltina, M. Losso, M. Parczewski, J. Lundgren, A. Mocroft, O. Kirk, M. Losso, M. Kundro, N. Vetter, R. Zangerle, V.M. Mitsura, O. Suetnov, N. Clumeck, S. De Wit, M. Delforge, E. Florence, L. Vandekerckhove, V. Hadziosmanovic, K. Kostov, J. Begovac, L. Machala, D. Jilich, D. Sedlacek, J. Nielsen, G. Kronborg, T. Benfield, M. Larsen, J. Gerstoft, T. Katzenstein, A.-.E. Hansen, P. Skinhoj, C. Pedersen, L. Ostergaard, U.B. Dragsted, L.N. Nielsen, K. Zilmer, S. Jelena, M. Ristola, C. Katlama, J.-. Viard, P.-. Girard, P. Vanhems, C. Pradier, F. Dabis, D. Neau, C. Duvivier, J. Rockstroh, Schmidt, J. van Lunzen, O. Degen, H.J. Stellbrink, M. Bickel, J.W. Goethe, J. Bogner, G. Fatkenheuer, J. Kosmidis, P. Gargalianos, G. Xylomenos, J. Perdios, H. Sambatakou, D. Banhegyi, M. Gottfredsson, F. Mulcahy, I. Yust, D. Turner, M. Burke, S. Pollack, G. Hassoun, H. Elinav, M. Haouzi, A. D'Arminio Monforte, R. Esposito, I. Mazeu, C. Mussini, C. Arici, R. Pristera, F. Mazzotta, A. Gabbuti, V. Vullo, M. Lichtner, A. Chirianni, E. Montesarchio, M. Gargiulo, G. D'Offizi, C. Taibi, A. Antinori, A. Lazzarin, A. Castagna, N. Gianotti, M. Galli, A. Ridolfo, B. Rozentale, I. Zeltina, S. Chaplinskas, T. Staub, R. Hemmer, P. Reiss, V. Ormaasen, A. Maeland, J. Bruun, B. Knysz, J. Gasiorowski, A. Horban, E. Bakowska, A. Grzeszczuk, R. Flisiak, B. A., M. Pynka, M. Parczewski, M. Beniowski, E. Mularska, H. Trocha, E. Jablonowska, E. Malolepsza, K. Wojcik, M. Doroana, M. Doroana, L. Caldeira, F. Maltez, D. Duiculescu, A. Rakhmanova, S. Buzunova, I. Khromova, E. Kuzovatova, D. Jevtovic, M. Mokras, D. Stanekova, J. Tomazic, J. Gonzalez-Lahoz, V. Soriano, P. Labarga, S. Moreno, J.M. Rodriguez, B. Clotet, A. Jou, R. Paredes, C. Tural, J. Puig, I. Bravo, J.M. Gatell, J.M. Miro, P. Domingo, M. Gutierrez, G. Mateo, M.A. Sambeat, J. Medrano, A. Blaxhult, L. Flamholc, A. Thalme, A. Sonnerborg, B. Ledergerber, R. Weber, P. Francioli, M. Cavassini, B. Hirschel, E. Boffi, H. Furrer, M. Battegay, L. Elzi, P. Vernazza, V. Frolov, G. Kutsyna, S. Servitskiy, A. Kuznetsova, G. Kyselyova, B. Gazzard, A.M. Johnson, E. Simons, A. Phillips, M.A. Johnson, A. Mocroft, C. Orkin, J. Weber, G. Scullard, M. Fisher, C. Leen. - In: HIV MEDICINE. - ISSN 1464-2662. - 16:9(2015 Oct), pp. 533-543. [10.1111/hiv.12254]

Changing utilization of Stavudine (d4T) in HIV-positive people in 2006-2013 in the EuroSIDA study

Podlekareva D.;Grint D.;Karpov I.;Vassilenko A.;Rakmanova A.;Mansinho K.;Chentsova N.;Kravchenko E.;Zeltina I.;Losso M.;Parczewski M.;Lundgren J.;Mocroft A.;Kirk O.;Losso M.;Kundro M.;Vetter N.;Zangerle R.;Mitsura V. M.;Suetnov O.;Clumeck N.;De Wit S.;Delforge M.;Florence E.;Vandekerckhove L.;Hadziosmanovic V.;Kostov K.;Begovac J.;Machala L.;Jilich D.;Sedlacek D.;Nielsen J.;Kronborg G.;Benfield T.;Larsen M.;Gerstoft J.;Katzenstein T.;Hansen A. -B. E.;Skinhoj P.;Pedersen C.;Ostergaard L.;Dragsted U. B.;Nielsen L. N.;Zilmer K.;Jelena Smidt;Ristola M.;Katlama C.;Viard J. -P.;Girard P. -M.;Vanhems P.;Pradier C.;Dabis F.;Neau D.;Duvivier C.;Rockstroh J.;Schmidt;van Lunzen J.;Degen O.;Stellbrink H. J.;Bickel M.;Goethe J. W.;Bogner J.;Fatkenheuer G.;Kosmidis J.;Gargalianos P.;Xylomenos G.;Perdios J.;Sambatakou H.;Banhegyi D.;Gottfredsson M.;Mulcahy F.;Yust I.;Turner D.;Burke M.;Pollack S.;Hassoun G.;Elinav H.;Haouzi M.;A. D'Arminio Monforte;Esposito R.;Mazeu I.;Mussini C.;Arici C.;Pristera R.;Mazzotta F.;Gabbuti A.;Vullo V.;Lichtner M.;Chirianni A.;Montesarchio E.;Gargiulo M.;D'Offizi G.;Taibi C.;Antinori A.;Lazzarin A.;Castagna A.;Gianotti N.;M. Galli;Ridolfo A.;Rozentale B.;Zeltina I.;Chaplinskas S.;Staub T.;Hemmer R.;Reiss P.;Ormaasen V.;Maeland A.;Bruun J.;Knysz B.;Gasiorowski J.;Horban A.;Bakowska E.;Grzeszczuk A.;Flisiak R.;A. Boron-Kaczmarska;Pynka M.;Parczewski M.;Beniowski M.;Mularska E.;Trocha H.;Jablonowska E.;Malolepsza E.;Wojcik K.;Doroana M.;Doroana M.;Caldeira L.;Maltez F.;Duiculescu D.;Rakhmanova A.;Buzunova S.;Khromova I.;Kuzovatova E.;Jevtovic D.;Mokras M.;Stanekova D.;Tomazic J.;Gonzalez-Lahoz J.;Soriano V.;Labarga P.;Moreno S.;Rodriguez J. M.;Clotet B.;Jou A.;Paredes R.;Tural C.;Puig J.;Bravo I.;Gatell J. M.;Miro J. M.;Domingo P.;Gutierrez M.;Mateo G.;Sambeat M. A.;Medrano J.;Blaxhult A.;Flamholc L.;Thalme A.;Sonnerborg A.;Ledergerber B.;Weber R.;Francioli P.;Cavassini M.;Hirschel B.;Boffi E.;Furrer H.;Battegay M.;Elzi L.;Vernazza P.;Frolov V.;Kutsyna G.;Servitskiy S.;Kuznetsova A.;Kyselyova G.;Gazzard B.;Johnson A. M.;Simons E.;Phillips A.;Johnson M. A.;Mocroft A.;Orkin C.;Weber J.;Scullard G.;Fisher M.;Leen C.

2015

Abstract

Objectives: The long-term side effects of stavudine (d4T) led to recommendations in 2009 to phase out use of this drug. We aimed to describe temporal patterns of d4T use across Europe. Methods: Patients taking combination antiretroviral therapy (cART) in EuroSIDA with follow-up after 1 January 2006 were included in the study. cART was defined as d4T-containing [d4T plus at least two other antiretrovirals (ARVs) from any class] or non-d4T-containing (at least three ARVs from any class, excluding d4T). Poisson regression was used to describe temporal changes in the prevalence of d4T use and factors associated with initiating d4T. Results: A total of 5850 patients receiving cART on 1 January 2006 were included in the current analysis, rising to 7768 patients on January 1 2013. During this time, the prevalence of d4T use fell from 11.2% to 0.7%, with an overall decline of 19% per 6 months [95% confidence interval (CI) 19-20%]. d4T use declined fastest in Northern Europe [26% (95% CI 23-29%) per 6 months], and slowest in Eastern Europe [17% (95% CI 16-19%) per 6 months]. In multivariable Poisson regression models, new d4T initiations decreased by 14% per 6 months [adjusted incidence rate ratio (aIRR) 0.86; 95% CI 0.80-0.91]. Factors associated with initiating d4T were residence in Eastern Europe (aIRR 4.31; 95% CI 2.17-9.98) versus other European regions and HIV RNA>400 copies/mL (aIRR 3.11; 95% CI 1.60-6.02) versus HIV RNA<400 copies/mL. Conclusions: d4T use has declined sharply since 2006 to low levels in most regions; however, a low but persistent level of d4T use remains in Eastern Europe, where new d4T initiations post 2006 are also more common. The reasons for the regional differences may be multifactorial, but it is important to ensure that all clinicians treating HIV-positive patients are aware of the potential harmful effects associated with d4T.

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	Parole chiave
	
			Combination antiretroviral therapy; Europe; EuroSIDA; HIV; Stavudine utilization; Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Europe; Female; Follow-Up Studies; HIV Infections; HIV-1; Humans; Male; Middle Aged; Prospective Studies; RNA, Viral; Regression Analysis; Stavudine
		
	Settori scientifico-disciplinari dell'articolo
	
			Settore MED/17 - Malattie Infettive
		
	Data di pubblicazione
	
			ott-2015
		
	Rivista in ANCE
	
			HIV MEDICINE
		
	DOI
	
			https://dx.doi.org/10.1111/hiv.12254
		
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			01 - Articolo su periodico

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