Comparison of dual nucleoside-analogue reverse-transcriptase inhibitor regimens with HIV-1 who have not previously been treated: the PENTA 5 randomized trial

Aboulker, J. P.; Babiker, A.; Compagnucci, A.; Darbyshire, J. H.; Debré, M.; Giaquinto, C.; Gibb, D. M.; Harper, L.; Saidi, Y.; Walker, As; Babiker, A.; Darbyshire, J.; Gibb, D. M.; Harper, L.; Johnson, D.; Kelleher, P.; Mcgee, L.; Newberry, A; Poland, A.; Walker, A. S.; Aboulker, J P.; Carrière, I.; Compagnucci, A.; Debré, M.; Eliette, V.; Leonardo, S.; Saidi, Y.; Aboulker, J. P.; Babiker, A.; Compagnucci, A.; Darbyshire, J.; Debré, M.; Gersten, M.; Giaquinto, C.; Gibb, D. M.; Jones, A.; Aboulker, J. P.; Babiker, A.; Blanche, S.; Bohlin, A. B.; Butler, K; Castelli Gattinara, G.; Clayden, P.; Darbyshire, J.; Debré, M.; R De Groot,; Faye, A.; Giaquinto, C.; Gibb, D. M.; Griscelli, C.; I Grosch Wörner,; Kind, C.; Lyall, H.; Levy, J.; Mellado Pena, M.; Nadal, D.; Peckham, C; Ramos Amador, J. T.; Rosado, L.; Rudin, C.; Scherpbier, H.; Sharland, M; Tovo, P. A.; Tudor Williams, G.; Valerius, N.; Volny Anne, A.; Wintergerst, U; Wahn, V.; Hill, C.; Lepage, P; Pozniak, A.; Vella, S.; Levy, J.; Hainaut, M.; Peltier, A.; Carlier, S.; Zissis, G.; Della Negra, M.; Queiroz, W.; Feitosa, L. P.; Oliveira, D; Mechinaud, F.; Ballerau, F.; Lepelletier, A.; Billaudel, S.; Ferre, V.; Grosch Wörner, I.; Weigel, R.; Seel, K.; Feiterna Sperling, C.; Ohlendorf, D.; Riße, G.; Müller, C.; Wahn, V.; Niehues, T.; Ndagijimana, J.; Horneff, G.; Vente, N.; Ganschow, R.; Simon, T.; Vossen, R.; Pfister, H; Wintergerst, U.; Notheis, G.; Strotmann, G.; Schlieben, S; Butler, K.; Hayes, E.; O’Mara, M.; Fanning, J.; Goggins, F.; Moriarty, S.; Byrne, M.; Battisti, L.; Duse, M.; Timpano, S.; Uberti, E.; Crispino, P.; Carrara, P.; Fomia, F.; Manca, A.; Galli, L.; de Martino, M.; Fioredda, F.; Pontali, E.; Cellini, M.; Baraldi, C.; Portolani, M.; Meacci, M.; Pietrosemoli, P.; Guarino, Alfredo; Spagnuolo, MARIA IMMACOLATA; Berni Canani, R.; Laccetti, P.; Gobbo, M.; Giaquinto, C.; Giacomet, V.; D’Elia, R.; Rampon, O.; Ruga, E.; de Rossi, A.; Zanchetta, M.; Caselli, D.; Maccabruni, A.; Cattaneo, E.; Landini, V; Castelli Gattinara, G.; Bernardi, S.; Krzysztofiak, A.; Tancredi, C.; Rossi, P.; Pansani, L.; Palomba, E.; Gabiano, C.; Mazza, A.; Rossetti, G.; Nicolin, R.; Timillero, A.; Rosado, L.; Candeias, F.; Santos, G; Ramos Ribeiro, M. L.; Almeida, M. C.; Lourenço, M. H.; Antunes, R.; Mellado Pena, M. J.; Carillo de Albornoz, M L.; Martinez Santos, P.; Ciria Calavia, L.; Serra Devecchi, J.; Delgado, O.; Matamoros, N.; Foot, A.; Kershaw, H.; Kelly, C.; Caul, O.; Tarnow Mordi, W.; Petrie, J.; Mcdowell, A.; Mcintyre, P.; Appleyard, K.; Sloper, K.; Shah, V.; Cheema, K.; Aali, A.; Mok, J.; Russell, R.; Brewster, A.; Richardson, N.; Burns, S.; Gibb, D.; Novelli, V.; Klein, N.; Mcgee, L.; Ewen, S.; Yeung, V.; Ball, C.; Himid, K.; Nayagam, D.; Graham, D.; Barrie, A.; Stringer, K.; Jones, S.; Weerasooriya, N.; Zuckerman, M.; Bracken, P.; Gibb, D.; Cooper, E.; Fisher, T.; Barrie, R.; Patel, U.; Van Someren, V.; Moshal, K.; Perry, L.; Gundlach, T.; Norman, J.; Sharland, M.; Richardson, M.; Donaghy, S.; Mitchla, Z.; Wells, C.; Booth, J.; Shipp, A.; Tudor Williams, G.; Lyall, H.; White, J.; Head, S.; Lambers, S.; O’Hara, K.; Stainsby, C.; Du Mont, G.; Solanki, T.; Swanton, S.; O’Shea, S.; Tilsey, A.; Kaye, S.; Finn, A.; Choo, S.; Lakshman, R.; Barr, L.; Bell, G.; Siddens, A.

Introduction Treatment options for children with HIV-1 are limited. We aimed to compare activity and safety of three dualnucleoside analogue reverse-transcriptase inhibitor (NRTI) regimens with or without a protease inhibitor in previously untreated children with HIV-1. Methods In our multicentre trial, we randomly assigned 36 children to zidovudine and lamivudine, 45 to zidovudine and abacavir, and 47 to lamivudine and abacavir. Children who were symptomfree (n=55) were also randomly assigned to receive nelfinavir or placebo. Children with more advanced disease received open-label nelfinavir (73). Primary endpoints were change in plasma HIV-1 RNA at 24 and 48 weeks for the NRTI comparison and occurrence of serious adverse events for both randomised comparisons. Analyses were by intention to treat. Findings Children had a median CD4 percentage of 22% (IQR 15–29) and a mean HIV-1 RNA concentration of 5·0 log copies/mL (SD 0·8). One child was lost to follow-up and one died of sepsis. At 48 weeks, in the zidovudine/lamivudine, zidovudine/abacavir, and lamivudine/abacavir groups, mean HIV-1 RNA had decreased by 1·71, 2·19, and 2·63 log copies/mL, respectively (estimated in absence of nelfinavir) (p=0·02 after adjustment for baseline factors). One child had a hypersensitivity reaction to abacavir; and three with possible reactions stopped abacavir. There were 24 serious adverse events—six in the symptom-free children (all on nelfinavir), but none were attributed to nelfinavir. Interpretation Regimens containing abacavir were more effective than zidovudine/lamivudine. Such regimens could be combined with protease inhibitors and non-nucleoside reverse transcriptase inhibitors for safe and effective treatment of previously untreated children with HIV-1.

Comparison of dual nucleoside-analogue reverse-transcriptase inhibitor regimens with HIV-1 who have not previously been treated: the PENTA 5 randomized trial / Aboulker, J. P.; Babiker, A.; Compagnucci, A.; Darbyshire, J. H.; Debré, M.; Giaquinto, C.; Gibb, D. M.; Harper, L.; Saidi, Y.; Walker, As; Babiker, A.; Darbyshire, J.; Gibb, D. M.; Harper, L.; Johnson, D.; Kelleher, P.; Mcgee, L.; Newberry, A; Poland, A.; Walker, A. S.; Aboulker, J P.; Carrière, I.; Compagnucci, A.; Debré, M.; Eliette, V.; Leonardo, S.; Saidi, Y.; Aboulker, J. P.; Babiker, A.; Compagnucci, A.; Darbyshire, J.; Debré, M.; Gersten, M.; Giaquinto, C.; Gibb, D. M.; Jones, A.; Aboulker, J. P.; Babiker, A.; Blanche, S.; Bohlin, A. B.; Butler, K; Castelli Gattinara, G.; Clayden, P.; Darbyshire, J.; Debré, M.; R De Groot, ; Faye, A.; Giaquinto, C.; Gibb, D. M.; Griscelli, C.; I Grosch Wörner, ; Kind, C.; Lyall, H.; Levy, J.; Mellado Pena, M.; Nadal, D.; Peckham, C; Ramos Amador, J. T.; Rosado, L.; Rudin, C.; Scherpbier, H.; Sharland, M; Tovo, P. A.; Tudor Williams, G.; Valerius, N.; Volny Anne, A.; Wintergerst, U; Wahn, V.; Hill, C.; Lepage, P; Pozniak, A.; Vella, S.; Levy, J.; Hainaut, M.; Peltier, A.; Carlier, S.; Zissis, G.; Della Negra, M.; Queiroz, W.; Feitosa, L. P.; Oliveira, D; Mechinaud, F.; Ballerau, F.; Lepelletier, A.; Billaudel, S.; Ferre, V.; Grosch Wörner, I.; Weigel, R.; Seel, K.; Feiterna Sperling, C.; Ohlendorf, D.; Riße, G.; Müller, C.; Wahn, V.; Niehues, T.; Ndagijimana, J.; Horneff, G.; Vente, N.; Ganschow, R.; Simon, T.; Vossen, R.; Pfister, H; Wintergerst, U.; Notheis, G.; Strotmann, G.; Schlieben, S; Butler, K.; Hayes, E.; O’Mara, M.; Fanning, J.; Goggins, F.; Moriarty, S.; Byrne, M.; Battisti, L.; Duse, M.; Timpano, S.; Uberti, E.; Crispino, P.; Carrara, P.; Fomia, F.; Manca, A.; Galli, L.; de Martino, M.; Fioredda, F.; Pontali, E.; Cellini, M.; Baraldi, C.; Portolani, M.; Meacci, M.; Pietrosemoli, P.; Guarino, Alfredo; Spagnuolo, MARIA IMMACOLATA; Berni Canani, R.; Laccetti, P.; Gobbo, M.; Giaquinto, C.; Giacomet, V.; D’Elia, R.; Rampon, O.; Ruga, E.; de Rossi, A.; Zanchetta, M.; Caselli, D.; Maccabruni, A.; Cattaneo, E.; Landini, V; Castelli Gattinara, G.; Bernardi, S.; Krzysztofiak, A.; Tancredi, C.; Rossi, P.; Pansani, L.; Palomba, E.; Gabiano, C.; Mazza, A.; Rossetti, G.; Nicolin, R.; Timillero, A.; Rosado, L.; Candeias, F.; Santos, G; Ramos Ribeiro, M. L.; Almeida, M. C.; Lourenço, M. H.; Antunes, R.; Mellado Pena, M. J.; Carillo de Albornoz, M L.; Martinez Santos, P.; Ciria Calavia, L.; Serra Devecchi, J.; Delgado, O.; Matamoros, N.; Foot, A.; Kershaw, H.; Kelly, C.; Caul, O.; Tarnow Mordi, W.; Petrie, J.; Mcdowell, A.; Mcintyre, P.; Appleyard, K.; Sloper, K.; Shah, V.; Cheema, K.; Aali, A.; Mok, J.; Russell, R.; Brewster, A.; Richardson, N.; Burns, S.; Gibb, D.; Novelli, V.; Klein, N.; Mcgee, L.; Ewen, S.; Yeung, V.; Ball, C.; Himid, K.; Nayagam, D.; Graham, D.; Barrie, A.; Stringer, K.; Jones, S.; Weerasooriya, N.; Zuckerman, M.; Bracken, P.; Gibb, D.; Cooper, E.; Fisher, T.; Barrie, R.; Patel, U.; Van Someren, V.; Moshal, K.; Perry, L.; Gundlach, T.; Norman, J.; Sharland, M.; Richardson, M.; Donaghy, S.; Mitchla, Z.; Wells, C.; Booth, J.; Shipp, A.; Tudor Williams, G.; Lyall, H.; White, J.; Head, S.; Lambers, S.; O’Hara, K.; Stainsby, C.; Du Mont, G.; Solanki, T.; Swanton, S.; O’Shea, S.; Tilsey, A.; Kaye, S.; Finn, A.; Choo, S.; Lakshman, R.; Barr, L.; Bell, G.; Siddens, A.. - In: THE LANCET. - ISSN 0140-6736. - STAMPA. - (2002), pp. 733-740.