Outcomes after reinitiating antiretroviral therapy in children randomized to planned treatment interruptions

Bunupuradah, T.; Duong, T.; Compagnucci, A.; Mcmaster, P.; Bernardi, S.; Kanjanavanit, S.; Rampon, O.; Faye, A.; Saïdi, Y.; Riault, Y.; De Rossi, A.; Klein, N.; Ananworanich, J.; Gibb, D.; J -P Aboulker,; Ananworanich, J.; Babiker, A.; Belfrage, E.; Bernardi, S.; Blanche, S.; A -B Bohlin,; Bologna, R.; Butler, K.; Castelli-Gattinara, G.; Castro, H.; Clayden, P.; Compagnucci, A.; H Darbyshire, J.; Debre, M.; Faye, A.; R De Groot,; M Della Negra,; A Di Biagio,; Duicelescu, D.; Faye, A.; Giaquinto, C.; Giacomet, V.; M Gibb, D.; Grosch-Worner, I.; Hainault, M.; Lallemant, M.; Levy, J.; Lyall, H.; Marczynska, M.; Mardarescu, M.; J Mellado Pena, M.; Nadal, D.; Niehues, T.; Peckham, C.; T Ramos Amador, J.; Rosado, L.; Rudin, C.; J Scherpbier, H.; Sharland, M.; Stevanovic, M.; Thorne, C.; A Tovo, P.; Tudor-Williams, G.; Valerius, N.; S Walker, A.; Welch, S.; Wintergerst, U.; P Aboulker, J.; Babiker, A.; M Burger, D.; Compagnucci, A.; H Darbyshire, J.; Debre, M.; Giaquinto, C.; M Gibb, D.; Green, H.; Harper, L.; Klein, N.; Lallemant, M.; Lyall, H.; Mofenson, L.; Moye, J.; Nadal, D.; Saıdi, Y.; M Burger, D.; R Cressey, T.; Jacqz-Aigrain, E.; Khoo, S.; Regazzi, M.; M Treluyer, J.; A De Rossi,; Klein, N.; Moye, J.; Ngo-Giang-Huong, N.; A Munoz Fernandez, M.; Pillay, D.; Hill, C.; Lepage, P.; Pozniak, A.; Vella, S.; Chene, G.; Vesikari, T.; Compagnucci, A.; Hadjou, G.; Leonardo, S.; Riault, Y.; Saidi, Y.; Babiker, A.; Bleier, J.; Buck, L.; Castro, H.; H Darbyshire, J.; Duong, T.; Farrelly, L.; Forcat, S.; M Gibb, D.; Harper, L.; Harrison, L.; Horton, J.; Johnson, D.; Moore, S.; Taylor, C.; S Walker, A.; Chalermpantmetagul, S.; R Cressey, T.; Peongjakta, R.; Khamjakkaew, W.; Thaninat, K.; Chailert, S.; Jourdain, G.; Lallemant, M.; S Le Coeur,; Ngo-Giang-Huong, N.; Corradini, S.; Costanzo, P.; T Le Thi, T.; Monpoux, F.; Mellul, S.; Caranta, I.; Boudjoudi, N.; Firtion, G.; Denon, M.; Charlemaine, E.; Picard, F.; Faye, A.; Hellier, E.; Heuninck, C.; Damond, F.; Alexandre, G.; Tricoire, J.; Antras, M.; Lachendowier, C.; Nicot, F.; Krivine, A.; Rivaux, D.; Wintergerst, U.; Notheis, G.; Strotmann, G.; Schlieben, S.; Giaquinto, C.; Rampon, O.; Boscolo, V.; Zanchetta, M.; Rosso, R.; Ginocchio, F.; Viscoli, C.; A Di Biagio,; Castelli-Gattinara, G.; Bernardi, S.; Martino, A.; Pontrelli, G.; Baldassar, S.; Concato, C.; Mazza, A.; Boscolo, V.; Rossetti, G.; Marczynska, M.; Dobosz, S.; Oldakowska, A.; Popielska, J.; Kaflik, M.; Stanczak, J.; Stanczack, G.; Dyda, T.; Kruk, M.; I Gonzalez Tome, M.; P Rojo Conejo,; R Delgado Garcıa,; T Fernandez Gonzalez, M.; Medin, G.; M Jose Mellado Pena,; P Martın Fontelos,; I Garcia Mellado, M.; F Medina, A.; Ascencion, B.; T Ramos Amador, J.; I Garcia Bermejo,; L Navarro Gomez, M.; Saavedra, J.; Prieto, C.; L Jimenez, J.; A Munoz-Fernandez, M.; A Garcia Torre,; I De Jose Gomez, M.; C Garcıa Rodriguez, M.; D Moreno Perez,; E Nunez Cuadros,; Asensi-Botet, F.; C Otero Reigada,; D Perez Tamarit, M.; Vilalta, R.; Moreno, M.; Nadal, D.; Schupbach, J.; Rutishauser, M.; Bunupuradah, T.; Ananworanich, J.; Butterworth, O.; Phasomsap, C.; Prasitsuebsai, W.; Chuanjaroen, T.; Jupimai, T.; Ubolyam, S.; Phanuphak, P.; Puthanakit, T.; Pancharoen, C.; Kanjanavanit, S.; Namwong, T.; Punsakoon, W.; Payakachat, S.; Chutima, D.; Raksasang, M.; Punsakoon, W.; Payakachat, S.; Lyall, H.; Tudor-Williams, G.; Foster, C.; Hamadache, D.; Campbell, S.; Newbould, C.; Monrose, C.; Abdulla, A.; Walley, A.; Melvin, D.; Patel, D.; Kaye, S.; Lyall, H.; Seery, P.; Hamadache, D.; Rankin, A.; Novelli, V.; M Gibb, D.; Klein, N.; Shingadia, D.; Moshal, K.; Flynn, J.; Clapson, M.; Farrelly, L.; Allen, A.; Spencer, L.; Rackstraw, C.; Ward, B.; Parkes, K.; Depala, M.; Jacobsen, M.; Poulsom, H.; Barkley, L.; Miah, J.; Melvin, D.; Lurie, P.; Keane, C.; Mcmaster, P.; Phipps, M.; Orendi, J.; Farmer, C.; Liebeschuetz, S.; Sodeinde, O.; Shingadia, D.; Wong, S.; Bostock, V.; Welch, S.; Heath, Y.; Scott, S.; Gandhi, K.; Lewis, P.; Daglish, J.; Miles, K.; Summerhill, L.; Pillay, D.; Subramaniam, B.; Weiner, L.; Famiglietti, M.; Rana, S.; Yu, P.; Roa, J.; Puga, A.; Haerry, A.

doi:10.1097/QAD.0b013e32835c1181

BACKGROUND: Excess risks for death/opportunistic disease in adults randomized to CD4-driven planned treatment interruption (PTI) in the Strategies for Management of Antiretroviral Therapy (SMART) trial remained after antiretroviral therapy (ART) re-initiation. Risks for children following PTI were evaluated in long-term follow-up of children in the PENTA 11 trial. METHODS: Children with HIV RNA below 50 copies/ml and CD4 at least 30% (2-6 years) or at least 500 cells/μl (7-15 years) were randomized to continuous ART (cART) or PTI in PENTA 11 (ISRCTN 36694210). After the end of the trial, all were recommended to resume ART. Data were collected annually and analysed up to the second year of visit. RESULTS: One hundred and one (51 cART, 50 PTI; median baseline age 9.2 years) children had median overall follow-up 4.6 (range 3.7-5.0) years. During 2-year post-trial period, there were no deaths or new Centers for Disease Control and Prevention (CDC) stage B/C events. Rate of clinical grade of at least two events was similar between PTI and cART [relative risk (RR) 1.03; 95% confidence interval (CI) 0.43, 2.50; P=0.94]. At 2 years, difference in absolute CD4% between PTI and cART was -1.6% (-4.5%; 1.3%; P=0.27), and proportions with HIV RNA below 50 copies/ml were 82 versus 86% (P=0.57), respectively; no differences in growth or fasting lipids were observed. Key predictors of greater CD4% recovery after re-initiating ART were higher CD4% at baseline (P<0.001) and longer time since ART re-initiation (P<0.001). During overall follow-up, 4 (8%) PTI versus 5 (10%) CT children switched ART for failure (P=0.75) and 9 (18%) versus 1 (2%) (P=0.008) substituted ART for simplification. CONCLUSIONS: No adverse clinical, immunological or virological consequences of PTI were observed 2 years after the end of PENTA 11 trial. Although ART interruption is not generally recommended, it may be an acceptable option for children, particularly when there is high risk of unplanned treatment interruptions. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Outcomes after reinitiating antiretroviral therapy in children randomized to planned treatment interruptions / B. Torsak, D. Trinh, C. Alexandra, M. Paddy, B. Stefania, K. Suparat, R. Osvalda, F. Albert, S. Yacine, R. Yoann, D.R. Anita, K. Nigel, A. Jintanat, G. Diana, J. -P Aboulker, J. Ananworanich, A. Babiker, E. Belfrage, S. Bernardi, S. Blanche, A. -B Bohlin, R. Bologna, K. Butler, G. Castelli-Gattinara, H. Castro, P. Clayden, A. Compagnucci, J. H Darbyshire, M. Debre, A. Faye, R. De Groot, M. Della Negra, A. Di Biagio, D. Duicelescu, A. Faye, C. Giaquinto, V. Giacomet, D. M Gibb, I. Grosch-Worner, M. Hainault, M. Lallemant, J. Levy, H. Lyall, M. Marczynska, M. Mardarescu, M. J Mellado Pena, D. Nadal, T. Niehues, C. Peckham, J. T Ramos Amador, L. Rosado, C. Rudin, H. J Scherpbier, M. Sharland, M. Stevanovic, C. Thorne, P. A Tovo, G. Tudor-Williams, N. Valerius, A. S Walker, S. Welch, U. Wintergerst, J. P Aboulker, A. Babiker, D. M Burger, A. Compagnucci, J. H Darbyshire, M. Debre, C. Giaquinto, D. M Gibb, H. Green, L. Harper, N. Klein, M. Lallemant, H. Lyall, L. Mofenson, J. Moye, D. Nadal, Y. Saıdi, D. M Burger, T. R Cressey, E. Jacqz-Aigrain, S. Khoo, M. Regazzi, J. M Treluyer, A. De Rossi, N. Klein, J. Moye, N. Ngo-Giang-Huong, M. A Munoz Fernandez, D. Pillay, C. Hill, P. Lepage, A. Pozniak, S. Vella, G. Chene, T. Vesikari, A. Compagnucci, G. Hadjou, S. Leonardo, Y. Riault, Y. Saidi, A. Babiker, J. Bleier, L. Buck, H. Castro, J. H Darbyshire, T. Duong, L. Farrelly, S. Forcat, D. M Gibb, L. Harper, L. Harrison, J. Horton, D. Johnson, S. Moore, C. Taylor, A. S Walker, S. Chalermpantmetagul, T. R Cressey, R. Peongjakta, W. Khamjakkaew, K. Thaninat, S. Chailert, G. Jourdain, M. Lallemant, S. Le Coeur, N. Ngo-Giang-Huong, S. Corradini, P. Costanzo, T. T Le Thi, F. Monpoux, S. Mellul, I. Caranta, N. Boudjoudi, G. Firtion, M. Denon, E. Charlemaine, F. Picard, A. Faye, E. Hellier, C. Heuninck, F. Damond, G. Alexandre, J. Tricoire, M. Antras, C. Lachendowier, F. Nicot, A. Krivine, D. Rivaux, U. Wintergerst, G. Notheis, G. Strotmann, S. Schlieben, C. Giaquinto, O. Rampon, V. Boscolo, M. Zanchetta, R. Rosso, F. Ginocchio, C. Viscoli, A. Di Biagio, G. Castelli-Gattinara, S. Bernardi, A. Martino, G. Pontrelli, S. Baldassar, C. Concato, A. Mazza, V. Boscolo, G. Rossetti, M. Marczynska, S. Dobosz, A. Oldakowska, J. Popielska, M. Kaflik, J. Stanczak, G. Stanczack, T. Dyda, M. Kruk, M. I Gonzalez Tome, P. Rojo Conejo, R. Delgado Garcıa, M. T Fernandez Gonzalez, G. Medin, M. Jose Mellado Pena, P. Martın Fontelos, M. I Garcia Mellado, A. F Medina, B. Ascencion, J. T Ramos Amador, I. Garcia Bermejo, M. L Navarro Gomez, J. Saavedra, C. Prieto, J. L Jimenez, M. A Munoz-Fernandez, A. Garcia Torre, M. I De Jose Gomez, M. C Garcıa Rodriguez, D. Moreno Perez, E. Nunez Cuadros, F. Asensi-Botet, C. Otero Reigada, M. D Perez Tamarit, R. Vilalta, M. Moreno, D. Nadal, J. Schupbach, M. Rutishauser, T. Bunupuradah, J. Ananworanich, O. Butterworth, C. Phasomsap, W. Prasitsuebsai, T. Chuanjaroen, T. Jupimai, S. Ubolyam, P. Phanuphak, T. Puthanakit, C. Pancharoen, S. Kanjanavanit, T. Namwong, W. Punsakoon, S. Payakachat, D. Chutima, M. Raksasang, W. Punsakoon, S. Payakachat, H. Lyall, G. Tudor-Williams, C. Foster, D. Hamadache, S. Campbell, C. Newbould, C. Monrose, A. Abdulla, A. Walley, D. Melvin, D. Patel, S. Kaye, H. Lyall, P. Seery, D. Hamadache, A. Rankin, V. Novelli, D. M Gibb, N. Klein, D. Shingadia, K. Moshal, J. Flynn, M. Clapson, L. Farrelly, A. Allen, L. Spencer, C. Rackstraw, B. Ward, K. Parkes, M. Depala, M. Jacobsen, H. Poulsom, L. Barkley, J. Miah, D. Melvin, P. Lurie, C. Keane, P. Mcmaster, M. Phipps, J. Orendi, C. Farmer, S. Liebeschuetz, O. Sodeinde, D. Shingadia, S. Wong, V. Bostock, S. Welch, Y. Heath, S. Scott, K. Gandhi, P. Lewis, J. Daglish, K. Miles, L. Summerhill, D. Pillay, B. Subramaniam, L. Weiner, M. Famiglietti, S. Rana, P. Yu, J. Roa, A. Puga, A. Haerry. - In: AIDS. - ISSN 0269-9370. - 27:4(2013), pp. 579-589. [10.1097/QAD.0b013e32835c1181]

Outcomes after reinitiating antiretroviral therapy in children randomized to planned treatment interruptions

Bunupuradah, Torsak;Duong, Trinh;Compagnucci, Alexandra;McMaster, Paddy;Bernardi, Stefania;Kanjanavanit, Suparat;Rampon, Osvalda;Faye, Albert;Saïdi, Yacine;Riault, Yoann;De Rossi, Anita;Klein, Nigel;Ananworanich, Jintanat;Gibb, Diana;J -P Aboulker;J Ananworanich;A Babiker;E Belfrage;S Bernardi;S Blanche;A -B Bohlin;R Bologna;K Butler;G Castelli-Gattinara;H Castro;P Clayden;A Compagnucci;J H Darbyshire;M Debre;A Faye;R de Groot;M della Negra;A di Biagio;D Duicelescu;A Faye;C Giaquinto;V. Giacomet;D M Gibb;I Grosch-Worner;M Hainault;M Lallemant;J Levy;H Lyall;M Marczynska;M Mardarescu;M J Mellado Pena;D Nadal;T Niehues;C Peckham;J T Ramos Amador;L Rosado;C Rudin;H J Scherpbier;M Sharland;M Stevanovic;C Thorne;P A Tovo;G Tudor-Williams;N Valerius;A S Walker;S Welch;U Wintergerst;J P Aboulker;A Babiker;D M Burger;A Compagnucci;J H Darbyshire;M Debre;C Giaquinto;D M Gibb;H Green;L Harper;N Klein;M Lallemant;H Lyall;L Mofenson;J Moye;D Nadal;Y Saıdi;D M Burger;T R Cressey;E Jacqz-Aigrain;S Khoo;M Regazzi;J M Treluyer;A De Rossi;N Klein;J Moye;N Ngo-Giang-Huong;M A Munoz Fernandez;D Pillay;C Hill;P Lepage;A Pozniak;S Vella;G Chene;T Vesikari;A Compagnucci;G Hadjou;S Leonardo;Y Riault;Y Saidi;A Babiker;J Bleier;L Buck;H Castro;J H Darbyshire;T Duong;L Farrelly;S Forcat;D M Gibb;L Harper;L Harrison;J Horton;D Johnson;S Moore;C Taylor;A S Walker;S Chalermpantmetagul;T R Cressey;R Peongjakta;W Khamjakkaew;K Thaninat;S Chailert;G Jourdain;M Lallemant;S Le Coeur;N Ngo-Giang-Huong;S Corradini;P Costanzo;T T Le Thi;F Monpoux;S Mellul;I Caranta;N Boudjoudi;G Firtion;M Denon;E Charlemaine;F Picard;A Faye;E Hellier;C Heuninck;F Damond;G Alexandre;J Tricoire;M Antras;C Lachendowier;F Nicot;A Krivine;D Rivaux;U Wintergerst;G Notheis;G Strotmann;S Schlieben;C Giaquinto;O Rampon;V Boscolo;M Zanchetta;R. Rosso;F Ginocchio;C Viscoli;A di Biagio;G Castelli-Gattinara;S Bernardi;A Martino;G Pontrelli;S Baldassar;C Concato;A Mazza;V Boscolo;G Rossetti;M Marczynska;S Dobosz;A Oldakowska;J Popielska;M Kaflik;J Stanczak;G Stanczack;T Dyda;M Kruk;M I Gonzalez Tome;P Rojo Conejo;R Delgado Garcıa;M T Fernandez Gonzalez;G Medin;M Jose Mellado Pena;P Martın Fontelos;M I Garcia Mellado;A F Medina;B Ascencion;J T Ramos Amador;I Garcia Bermejo;M L Navarro Gomez;J Saavedra;C Prieto;J L Jimenez;M A Munoz-Fernandez;A Garcia Torre;M I de Jose Gomez;M C Garcıa Rodriguez;D Moreno Perez;E Nunez Cuadros;F Asensi-Botet;C Otero Reigada;M D Perez Tamarit;R Vilalta;Molina Moreno;D Nadal;J Schupbach;M Rutishauser;T Bunupuradah;J Ananworanich;O Butterworth;C Phasomsap;W Prasitsuebsai;T Chuanjaroen;T Jupimai;S Ubolyam;P Phanuphak;T Puthanakit;C Pancharoen;S Kanjanavanit;T Namwong;W Punsakoon;S Payakachat;D Chutima;M Raksasang;W Punsakoon;S Payakachat;H Lyall;G Tudor-Williams;C Foster;D Hamadache;S Campbell;C Newbould;C Monrose;A Abdulla;A Walley;D Melvin;D Patel;S Kaye;H Lyall;P Seery;D Hamadache;A Rankin;V Novelli;D M Gibb;N Klein;D Shingadia;K Moshal;J Flynn;M Clapson;L Farrelly;A Allen;L Spencer;C Rackstraw;B Ward;K Parkes;M Depala;M Jacobsen;H Poulsom;L Barkley;J Miah;D Melvin;P Lurie;C Keane;P McMaster;M Phipps;J Orendi;C Farmer;S Liebeschuetz;O Sodeinde;D Shingadia;S Wong;V Bostock;S Welch;Y Heath;S Scott;K Gandhi;P Lewis;J Daglish;K Miles;L Summerhill;D Pillay;B Subramaniam;L Weiner;M Famiglietti;S Rana;P Yu;J Roa;A Puga;A Haerry

2013

Abstract

BACKGROUND: Excess risks for death/opportunistic disease in adults randomized to CD4-driven planned treatment interruption (PTI) in the Strategies for Management of Antiretroviral Therapy (SMART) trial remained after antiretroviral therapy (ART) re-initiation. Risks for children following PTI were evaluated in long-term follow-up of children in the PENTA 11 trial. METHODS: Children with HIV RNA below 50 copies/ml and CD4 at least 30% (2-6 years) or at least 500 cells/μl (7-15 years) were randomized to continuous ART (cART) or PTI in PENTA 11 (ISRCTN 36694210). After the end of the trial, all were recommended to resume ART. Data were collected annually and analysed up to the second year of visit. RESULTS: One hundred and one (51 cART, 50 PTI; median baseline age 9.2 years) children had median overall follow-up 4.6 (range 3.7-5.0) years. During 2-year post-trial period, there were no deaths or new Centers for Disease Control and Prevention (CDC) stage B/C events. Rate of clinical grade of at least two events was similar between PTI and cART [relative risk (RR) 1.03; 95% confidence interval (CI) 0.43, 2.50; P=0.94]. At 2 years, difference in absolute CD4% between PTI and cART was -1.6% (-4.5%; 1.3%; P=0.27), and proportions with HIV RNA below 50 copies/ml were 82 versus 86% (P=0.57), respectively; no differences in growth or fasting lipids were observed. Key predictors of greater CD4% recovery after re-initiating ART were higher CD4% at baseline (P<0.001) and longer time since ART re-initiation (P<0.001). During overall follow-up, 4 (8%) PTI versus 5 (10%) CT children switched ART for failure (P=0.75) and 9 (18%) versus 1 (2%) (P=0.008) substituted ART for simplification. CONCLUSIONS: No adverse clinical, immunological or virological consequences of PTI were observed 2 years after the end of PENTA 11 trial. Although ART interruption is not generally recommended, it may be an acceptable option for children, particularly when there is high risk of unplanned treatment interruptions. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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	Parole chiave
	
				antiretroviral therapy; ART re-initiation; HIV-infected children; PTI; treatment interruption; Acquired Immunodeficiency Syndrome; Adolescent; Anti-HIV Agents; CD4-Positive T-Lymphocytes; Child; DNA, Viral; Disease Progression; Drug Administration Schedule; Europe; Female; Follow-Up Studies; HIV Seropositivity; Humans; Male; RNA, Viral; Risk Assessment; Thailand; Treatment Outcome; United States; Viral Load; Antiretroviral Therapy, Highly Active; Immunology and Allergy; Immunology; Infectious Diseases
			
	Settori scientifico-disciplinari dell'articolo (sola visualizzazione)
	
				Settore MED/38 - Pediatria Generale e Specialistica
			
	Settori scientifico-disciplinari dell'articolo (validi dal 09/05/2024)
	
				Settore MEDS-20/A - Pediatria generale e specialistica
			
	Data di pubblicazione
	
				2013
			
	Rivista in ANCE
	
				AIDS
			
	DOI
	
				https://dx.doi.org/10.1097/QAD.0b013e32835c1181
			
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				Article (author)
			
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				01 - Articolo su periodico

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