Author: "Alexandra Compagnucci" - Searchworks@Jio Institute Digital Library Search Results

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1. Nucleoside/nucleotide reverse transcriptase inhibitor sparing regimen with once daily integrase inhibitor plus boosted darunavir is non-inferior to standard of care in virologically-suppressed children and adolescents living with HIV – Week 48 results of the randomised SMILE Penta-17-ANRS 152 clinical trialResearch in context

Author: Alexandra Compagnucci, Man K. Chan, Yacine Saïdi, Tim R. Cressey, Alasdair Bamford, Yoann Riault, Alexandra Coelho, Aoife Nolan, Suwalai Chalermpantmetagul, Gabija Morkunaite, Pauline Amuge, Victor Musiime, Avy Violari, Mark Cotton, Adeodata R. Kekitiinwa, Elizabeth Kaudha, Marisa Groenewald, Afaaf A. Liberty, Suparat Kanjanavanit, Alla Volokha, Rosa Bologna, Noris Pavia Ruz, Luis Prieto Tato, Paolo Paioni, Laura Marques, Véronique Reliquet, Tim Niehues, Steven B. Welch, Deborah Ford, Carlo Giaquinto, Diana M. Gibb, Abdel Babiker, Jose Tomas Ramos Amador, A. Compagnucci, Y. Saidi, Y. Riault, A. Coelho, C. Kouakam, L. Picault, M. Ndiaye, L. Meyer, C. Cagnot, S. Circosta, L. Léger, S. Simanic, A. Arulananthan, D.M. Gibb, A. Babiker, M. Chan, D. Ford, F. Hudson, L. Harper, A. Bamford, A. Nolan, K. Widuch, S. Townsend, N. Van-Looy, L. Gao, E. Little, A. Turkova, S. Fabiane, J. Calvert, J. Blackstone, K. Scott, J. Inshaw, A. Nunn, A. Nardone, D. Bilardi, T.R. Cressey, S. Chalermpantmetagul, W. Khamduang, G. Jourdain, N. Ngo Giang Huong, D. Chinwong, C. Saenjum, R. Peongjakta, P. Sukrakanchana, L. Laomanit, A. Kaewbundit, J. Khamkon, K. Than-in-at, C. Meeboon, W. Sripaoraya, N. Krueduangkam, N. Kruenual, W. Khamjakkaew, S. Klinprung, C. Giaquinto, G. Morkunaite, D. Hirt, L. Prieto Tato, T. Niehues, D. Plonné, C. Morén, T. Noguera, M.A. Muñoz Fernández, R. Bologna, S. Arazi, A.G. Fedullo, M. Taicz, E. Vicentini, M. Moragas, A. Mangano, M. Dell’Orso, M. Gatto, V. Reliquet, A. Soria, E. Paredes, N. Chereau, M. Tching Sin, L. Flet, A. Rodallec, C. Hemon, N. Elenga, M.D. Terrine, N. Blaise, S. Augustin, P. Mespoulhe, H. Pouchain, N. Pavia-Ruz, R. Muñoz- Hernández, A. Neri-Macias, M.D. Jarillo-Quijada, C. Espinosa-Sotero, L. Marques, C. Teixeira, A. Fernandes, R. Nunes, H. Nascimento, J. Tuna, A. Padrao, I. Ferraz, A.C. Mendes, C. Correira, H. Pinheiro, A.C. Matos, A.C. Sampaio, A. Oliveira, A. Caldeira, M. Tavares, A. Reis Melo, C. Castro, C. Faria, C. Prucha, R. Ribeiro, F. Monteiro, M.F. Candeias, T. Silva Milhiero, E. Gomes Neves, R. Corte-Real, M. Morgado, D. Mendes, M. Cardão, A. Violari, N. Ramsagar, A. Liberty, M. Nyati, L. Maseko, M. Khunene, S. Mkhize, Z. Essack, N. Akoojee, U. Singh, Y. Fourie, S. Govender, A. Vadee, R. Lakha, J. Erasmus, A. Mamiane, T. Daniel, P. Bhana, N. Maduna, M. Cotton, M. Groenewald, G. Slade, J. Coetzee, L. Ganger, S. Weldon, M. Wessels, L. Hoorn, S. Pieterse, C. Makola, K. Smith, M. Isaacs, A. Cweya, S. Fry, S. Barnabas, M. Theunissen, N. Nduna, M. Smuts, P. Rojo Conejo, C. Epalza, M. Fernández, M.J. Mellado Peña, T. Sainz Costa, L. Escosa García, P. Gomez Salcedo, C. Fortuny Guasch, T. Noguera Julian, C. Estepa, M. Cubells, E. Sans, E. Bruno, L. Prieto, P. Mendez García, A. Murciano Cabeza, M. Coto, R. Torrent, M. Torres Arauz, M. Navarro Gómez, A. Mur, S. Guillén Martin, M. Moreno, J.T. Ramos Amador, I. Garcia, C. Kalhert, T. Wachinger, B. Wohlwend, S. Hafner, G. Dollenmaier, P. Paioni, R. Signorell, J. Boni, A. Duppenthaler, B. Mann, C. Saegesser, M. Barbani, C. Ngampiyaskul, P. Greetanukroh, P. Khannak, P. Tearsansern, W. Chamjamrat, N. Chanto, T. Thapwai, K. Thungkham, P. Puangmalai, C. Ruklao, P. Ounchanum, S. Khusuwan, S. Denjanta, Y. Thaweesombat, J. Thewsoongnoen, K. Kaewmamueng, P. Kamboua, S. Pongprapass, W. Srisuk, A. Kongponoi, J. Limplertjareanwanich, S. Kanjanavanit, C. Saewtrakool, P. Yingyong, D. Chutima, R. Junkaew, T. Chankun, U. Srirompotong, P. Sudsaard, K. Kongsuk, T. Petpranee, S. Srirojana, D. Donngernl, A. Kamkoonmongkol, N. Na Kalasin, P. Phunkhum, A.R. Kekitiinwa, P. Amuge, D. Bbuye, J. Nalubwama, S. Namanda, M. Nsibuka Kisekka, A. Kirabira, L. Lawrence, G. Agaba, G. Ahimbisibwe, A. Nalugo, F. Namuli, R. Kadhuba, R. Namuddu, I. Nabwire, L. Kiyimba, A. Baita, J. Tikabibamu, L. Nakandi, G.P. Kisitu, N. Nabukeera Barung, C.M. Kityo, V. Musiime, E. Kaudha, A. Nanduudu, E. Mujyambere, S.P. Labeja Ocitti, J. Ategeka, E. Nambi, R. Nazzinda, D. Rutebarika, R. Basiimwa, R. Mbabazi, P. Kyobutungi, M. Nabalamba, A. Nakalyango, J. Tumusiime, S. Nakabuye, J. Mwebaza, S. Oruk, J. Namusanje, A. Musiime, L. Mugarura, M. Ojok, J. Kitabalwa, C. Katemba, M. Nannungi, E. Bagirigomwa, D. Odoch, E. Rubanga, D. Mulima, E.L. Babu, D. Baliruno, C. Inyakuwal, E.D. Williams, A. Mulindwa, A. Uyungrwoth, I. Raus, O. Mostovenko, T. Stepchenkova, A. Volokha, N. Primak, J. Kenny, A. Callaghan, M. Ahmad, S. Vergnano, M. Ross, F. Manyi, D. Nayagam, S. Hawkins, C. Ball, E. Hamlyn, C. Gilmour, S. Gilmour-White, S. Doshi, E. Fuller, A. Adebayo, K. Tupper, E. Nsirim, S. Welch, J. Daglish, L. Thrasyvoulou, E. Irvine, K. Gandhi, Y. Vaughn-Gordon, and N. Sibanda
Subjects: HIV, Children, Adolescents, Randomised, Paediatrics, Dual therapy, Medicine (General), R5-920
Abstract: Summary: Background: Integrase inhibitor (INSTI) with boosted darunavir (DRV/r), a regimen with a high-resistance barrier, avoiding NRTI toxicities, might be a switching option in children living with HIV (CLWHIV). Methods: SMILE is a randomised non-inferiority trial evaluating safety and antiviral efficacy of once-daily INSTI + DRV/r vs. continuing on current standard-of-care (SOC) triple ART (2NRTI + boosted PI/NNRTI) in virologically-suppressed CLWHIV aged 6–18 years. The primary outcome is the proportion with confirmed HIV-RNA ≥50 copies/mL by week 48, estimated by Kaplan–Meier method. Non-inferiority margin was 10%. Registration number for SMILE are: ISRCTN11193709, NCT #: NCT02383108. Findings: Between 10th June 2016 and 30th August 2019, 318 participants were enrolled from Africa 53%, Europe 24%, Thailand 15% and Latin America 8%, 158 INSTI + DRV/r [153 Dolutegravir (DTG); 5 Elvitegravir (EVG)], 160 SOC. Median (range) age was 14.7 years (7.6–18.0); CD4 count 782 cells/mm3 (227–1647); 61% female. Median follow-up was 64.3 weeks with no loss to follow-up. By 48 weeks, 8 INSTI + DRV/r vs. 12 SOC had confirmed HIV-RNA ≥50 copies/mL; difference (INSTI + DRV/r-SOC) −2.5% (95% CI: −7.6, 2.5%), showing non-inferiority. No major PI or INSTI resistance mutations were observed. There were no differences in safety between arms. By week 48, difference (INSTI + DRV/r-SOC) in mean CD4 count change from baseline was −48.3 cells/mm3 (95% CI: −93.4, −3.2; p = 0.036). Difference (INSTI + DRV/r-SOC) in mean HDL change from baseline was −4.1 mg/dL (95% CI: −6.7, −1.4; p = 0.003). Weight and Body Mass Index (BMI) increased more in INSTI + DRV/r than SOC [difference: 1.97 kg (95% CI: 1.1, 2.9; p
Published: 2023
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2. ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing

Author: Cecilia L. Moore, Anna Turkova, Hilda Mujuru, Adeodata Kekitiinwa, Abbas Lugemwa, Cissy M. Kityo, Linda N. Barlow-Mosha, Tim R. Cressey, Avy Violari, Ebrahim Variava, Mark F. Cotton, Moherndran Archary, Alexandra Compagnucci, Thanyawee Puthanakit, Osee Behuhuma, Yacine Saϊdi, James Hakim, Pauline Amuge, Lorna Atwine, Victor Musiime, David M. Burger, Clare Shakeshaft, Carlo Giaquinto, Pablo Rojo, Diana M. Gibb, Deborah Ford, and the ODYSSEY Trial Team
Subjects: Randomized control trial, Basket trial, HIV, Paediatric, Efficacy, Safety, Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested pharmacokinetic (PK) sub-studies which evaluated pragmatic World Health Organization (WHO) weight-band-based DTG dosing and opened recruitment to children
Published: 2021
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3. Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents and young adults (BREATHER): Extended follow-up results of a randomised, open-label, non-inferiority trial.

Author: Anna Turkova, Cecilia L Moore, Karina Butler, Alexandra Compagnucci, Yacine Saïdi, Victor Musiime, Annet Nanduudu, Elizabeth Kaudha, Tim R Cressey, Suwalai Chalermpantmetagul, Karen Scott, Lynda Harper, Samuel Montero, Yoann Riault, Torsak Bunupuradah, Alla Volokha, Patricia M Flynn, Rosa Bologna, Jose T Ramos Amador, Steven B Welch, Eleni Nastouli, Nigel Klein, Carlo Giaquinto, Deborah Ford, Abdel Babiker, Diana M Gibb, and BREATHER (PENTA 16) trial Group
Subjects: Medicine, Science
Abstract: BackgroundWeekends off antiretroviral therapy (ART) may help engage HIV-1-infected young people facing lifelong treatment. BREATHER showed short cycle therapy (SCT; 5 days on, 2 days off ART) was non-inferior to continuous therapy (CT) over 48 weeks. Planned follow-up was extended to 144 weeks, maintaining original randomisation.MethodsBREATHER was an open-label, non-inferiority trial. Participants aged 8-24yrs with virological suppression on efavirenz-based first-line ART were randomised 1:1, stratified by age and African/non-African sites, to remain on CT or change to SCT. The Kaplan-Meier method was used to estimate the proportion of participants with viral rebound (confirmed VL≥50 copies/mL) under intent-to-treat at 48 weeks (primary outcome), and in extended follow-up at 96, 144, and 192 weeks. SCT participants returned to CT following viral rebound, 3 VL blips or discontinuation of efavirenz.FindingsOf 199 participants (99 SCT, 100 CT), 97 per arm consented to extended follow-up. Median follow-up was 185.3 weeks (IQR 160.9-216.1). 69 (70%) SCT participants remained on SCT at last follow-up. 105 (53%) were male, baseline median age 14 years (IQR 12-18), median CD4 count 735 cells/μL (IQR 576-968). 16 SCT and 16 CT participants had confirmed VL≥50 copies/mL by the end of extended follow-up (HR 1.00, 95% CI 0.50-2.00). Estimated difference in percentage with viral rebound (SCT minus CT) by week 144 was 1.9% (90% CI -6.6-10.4; p = 0.72) and was similar in a per-protocol analysis. There were no significant differences between arms in proportions of participants with grade 3/4 adverse events (18 SCT vs 16 CT participants; p = 0.71) or ART-related adverse events (10 vs 12; p = 0.82). 20 versus 8 serious adverse events (SAEs) were reported in 16 SCT versus 4 CT participants, respectively (p = 0.005 comparing proportions between groups; incidence rate ratio 2.49, 95%CI 0.71-8.66, p = 0.15). 75% of SAEs (15 SCT, 6 CT) were hospitalisations for a wide range of conditions. 3 SCT and 6 CT participants switched to second-line ART following viral failure (p = 0.50).ConclusionsSustainable non-inferiority of virological suppression in young people was shown for SCT versus CT over median 3.6 years. Standard-dose efavirenz-based SCT is a viable option for virologically suppressed HIV-1 infected young people on first-line ART with 3-monthly VL monitoring.Trial registrationEudraCT 2009-012947-40 ISRCTN 97755073 ClinicalTrials.gov NCT01641016.
Published: 2018
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4. Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children

Author: Anna, Turkova, Ellen, White, Hilda A, Mujuru, Adeodata R, Kekitiinwa, Cissy M, Kityo, Avy, Violari, Abbas, Lugemwa, Tim R, Cressey, Philippa, Musoke, Ebrahim, Variava, Mark F, Cotton, Moherndran, Archary, Thanyawee, Puthanakit, Osee, Behuhuma, Robin, Kobbe, Steven B, Welch, Mutsa, Bwakura-Dangarembizi, Pauline, Amuge, Elizabeth, Kaudha, Linda, Barlow-Mosha, Shafic, Makumbi, Nastassja, Ramsagar, Chaiwat, Ngampiyaskul, Godfrey, Musoro, Lorna, Atwine, Afaaf, Liberty, Victor, Musiime, Dickson, Bbuye, Grace M, Ahimbisibwe, Suwalai, Chalermpantmetagul, Shabinah, Ali, Tatiana, Sarfati, Ben, Wynne, Clare, Shakeshaft, Angela, Colbers, Nigel, Klein, Sarah, Bernays, Yacine, Saïdi, Alexandra, Coelho, Tiziana, Grossele, Alexandra, Compagnucci, Carlo, Giaquinto, Pablo, Rojo, Deborah, Ford, Diana M, Gibb, and Anna, Goodman
Subjects: Oral, Cyclopropanes, Male, Adolescent, Pyridones, Administration, Oral, HIV Infections, 3-Ring, Article, Piperazines, Drug Therapy, Heterocyclic Compounds, Oxazines, Humans, HIV Integrase Inhibitors, Child, Preschool, Alkynes, Anti-Retroviral Agents, Benzoxazines, Child, Preschool, Cholesterol, Drug Therapy, Combination, Female, HIV Protease Inhibitors, Heterocyclic Compounds, 3-Ring, Viral Load, HIV-1, General Medicine, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Administration, Combination
Abstract: Item does not contain fulltext BACKGROUND: Children with human immunodeficiency virus type 1 (HIV-1) infection have limited options for effective antiretroviral treatment (ART). METHODS: We conducted an open-label, randomized, noninferiority trial comparing three-drug ART based on the HIV integrase inhibitor dolutegravir with standard care (non-dolutegravir-based ART) in children and adolescents starting first- or second-line ART. The primary end point was the proportion of participants with virologic or clinical treatment failure by 96 weeks, as estimated by the Kaplan-Meier method. Safety was assessed. RESULTS: From September 2016 through June 2018, a total of 707 children and adolescents who weighed at least 14 kg were randomly assigned to receive dolutegravir-based ART (350 participants) or standard care (357). The median age was 12.2 years (range, 2.9 to 18.0), the median weight was 30.7 kg (range, 14.0 to 85.0), and 49% of the participants were girls. By design, 311 participants (44%) started first-line ART (with 92% of those in the standard-care group receiving efavirenz-based ART), and 396 (56%) started second-line ART (with 98% of those in the standard-care group receiving boosted protease inhibitor-based ART). The median follow-up was 142 weeks. By 96 weeks, 47 participants in the dolutegravir group and 75 in the standard-care group had treatment failure (estimated probability, 0.14 vs. 0.22; difference, -0.08; 95% confidence interval, -0.14 to -0.03; P = 0.004). Treatment effects were similar with first- and second-line therapies (P = 0.16 for heterogeneity). A total of 35 participants in the dolutegravir group and 40 in the standard-care group had at least one serious adverse event (P = 0.53), and 73 and 86, respectively, had at least one adverse event of grade 3 or higher (P = 0.24). At least one ART-modifying adverse event occurred in 5 participants in the dolutegravir group and in 17 in the standard-care group (P = 0.01). CONCLUSIONS: In this trial involving children and adolescents with HIV-1 infection who were starting first- or second-line treatment, dolutegravir-based ART was superior to standard care. (Funded by ViiV Healthcare; ODYSSEY ClinicalTrials.gov number, NCT02259127; EUDRACT number, 2014-002632-14; and ISRCTN number, ISRCTN91737921.).
Published: 2021

5. Once-daily dolutegravir-based antiretroviral therapy in infants and children living with HIV from age 4 weeks: results from the below 14 kg cohort in the randomised ODYSSEY trial

Author: Pauline Amuge, Abbas Lugemwa, Ben Wynne, Hilda A Mujuru, Avy Violari, Cissy M Kityo, Moherndran Archary, Ebrahim Variava, Ellen White, Rebecca M Turner, Clare Shakeshaft, Shabinah Ali, Kusum J Nathoo, Lorna Atwine, Afaaf Liberty, Dickson Bbuye, Elizabeth Kaudha, Rosie Mngqibisa, Modehei Mosala, Vivian Mumbiro, Annet Nanduudu, Rogers Ankunda, Lindiwe Maseko, Adeodata R Kekitiinwa, Carlo Giaquinto, Pablo Rojo, Diana M Gibb, Anna Turkova, Deborah Ford, Amina Farhana Mehar (nee Abdulla), Pattamukkil Abraham, Elaine Abrams, Judith Acero, Gerald Muzorah Agaba, Grace Ahimbisibwe, Barbara Ainebyoona, Winnie Akobye, Yasmeen Akhalwaya, Nazim Akoojee, Shabinah S. Ali, Catherine Andrea, Maria Angeles Muñoz Fernandez, Diana Antonia Rutebarika, Suvaporn Anugulruengkitt, Tsitsi Apollo, Ronelle Arendze, Juliet Ategeka, Eunice Atim, Abdel Babiker, Sarah Babirye, Enock Babu, Edward Bagirigomwa, Angella Baita, David Balamusani, Patsy Baliram, David Baliruno, Colin Ball, Henry Balwa, Alasdair Bamford, Srini Bandi, Dominique Barker, Linda Barlow-Mosha, Shazia Begum, Osee Behuhuma, Sarah Bernays, Rogers Besigye, Maria Bester, Joyline Bhiri, Davide Bilardi, Kristien Bird, Pauline Bollen, Chiara Borg, Anne-Marie Borges Da Silva, Jackie Brown, Elena Bruno, Torsak Bunupuradah, David Burger, Nomzamo Buthelezi, Mutsa Bwakura-Dangarembizi, Africanus Byaruhanga, Joanna Calvert, Petronelle Casey, Haseena Cassim, Sphiwee Cebekhulu, Sanuphong Chailert, Suwalai Chalermpantmetagul, Wanna Chamjamrat, Man Chan, Precious Chandiwana, Thannapat Chankun, Sararut Chanthaburanun, Nuttawut Chanto, Ennie Chidziva, Minenhle Chikowore, Joy Chimanzi, Dujrudee Chinwong, Stuart Chitongo, Moses Chitsamatanga, Joshua Choga, Duangrat Chutima, Polly Clayden, Alexandra Coelho, Angela Colbers, Alexandra Compagnucci, Ana Constança Mendes, Magda Conway, Mark F. Cotton, Jane Crawley, Tim R. Cressey, Jacky Crisp, Ana Cristina Matos, Sumaya Dadan, Jacqui Daglish, Siva Danaviah, Tseleng Daniel, Anita De Rossi, Sukanda Denjanta, Els Dobbels, Maria Dowie, Prosper Dube, Benedictor Dube, Nimisha Dudakia, Alice Elwana, Cristina Epalza, David Eram, Juan Erasmus, Peter Erim, Luis Escosa Garcia, Zaakirah Essack, Carolina Estepa, Monica Etima, Alexandre Fernandes, Maite Fernandez, Felicity Fitzgerald, Jacquie Flynn, Claudia Fortuny Guasch, Caroline Foster, George Fourie, Yolandie Fourie, Sophie Foxall, Derusha Frank, Kate Gandhi, India Garcia, Kathleen Gartner, Joshua Gasa, Gugu Gasa, Diana M. Gibb, Coral Gomez Rico, Daniel Gomez-Pena, Secrecy Gondo, Anna Goodman, Maria Gorreti Nakalema, Winnie Gozhora, Pisut Greetanukroh, Biobanco Gregorio Maranon, Tiziana Grossele, Shamiso Gwande, Tapiwa Gwaze, Tsitsi Gwenzi, James Hakim, Emmanuel Hakiza, Abdul Hamid Kaka, Ashley Harley, Mornay Isaacs, Richard Isabirye, Wilber Ishemunyoro, Tom Jacobs, Lungile Jafta, Nasir Jamil, Anita Janse Janse van Rensburg, Vinesh Jeaven, Maria José Mellado Peña, Gonzague Jourdain, Katabalwa Juliet, Thidarat Jumpimai, Raungwit Junkaew, Thidarat Jupimai, Winfred Kaahwa, Mildred Kabasonga, Olivia Kaboggoza, Rose Jacqueline Kadhuba, Ampika Kaewbundit, Kanyanee Kaewmamueng, Bosco Kafufu, Brenda Kakayi, Phakamas Kamboua, Suparat Kanjanavanit, Gladys Kasangaki, Naruporn Kasipong, Miriam Kasozi, Hajira Kataike, Chrispus Katemba, Nkata Kekane, Adeodata R. Kekitiinwa, Edridah Keminyeto, Woottichai Khamduang, Warunee Khamjakkaew, Jiraporn Khamkon, Sasipass Khannak, Orapin Khatngam, Tassawan Khayanchoomnoom, Busi Khumalo, Mirriam Khunene, Suwimon Khusuwan, Phionah Kibalama, Robinah Kibenge, Anthony Kirabira, Cissy M. Kityo, Lameck Kiyimba, Nigel Klein, Soraya Klinprung, Robin Kobbe, Olivia Kobusingye, Josephine Kobusungye, Areerat Kongponoi, Christoph Königs, Olivier Koole, Christelle Kouakam, Nitinart Krueduangkam, Namthip Kruenual, Nuananong Kunjaroenrut, Raymonds Kyambadde, Priscilla Kyobutungi, Flavia Kyomuhendo, Erinah Kyomukama, Reshma Lakha, Cleopatra Langa, Laddawan Laomanit, Emily Lebotsa, Prattana Leenasirimakul, Lawrence Lekku, Sarah Lensen, Valériane Leroy, Jin Li, Juthamas Limplertjareanwanich, Emma Little, Ezra Lutalo, Jose Luis Jimenez, Hermione Lyall, Candice MacDonald, Gladness Machache, Penelope Madlala, Tryphina Madonsela, Nomfundo Maduna, Joel Maena, Apicha Mahanontharit, Collin Makanga, Candice Makola, Shafic Makumbi, Lucille Malgraaf, Angelous Mamiane, Felicia Mantkowski, Wendy Mapfumo, Laura Marques, Agnes Mary Mugagga, Tshepiso Masienyane, Ruth Mathiba, Farai Matimba, Sajeeda Mawlana, Emmanuel Mayanja, Fatima Mayat, Ritah Mbabazi, Nokuthula Mbadaliga, Faith Mbasani, Kathleen McClaughlin, Helen McIlleron, Watchara Meethaisong, Patricia Mendez Garcia, Annet Miwanda, Carlota Miranda, Siphiwe Mkhize, Kgosimang Mmolawa, Fatima Mohamed, Tumelo Moloantoa, Maletsatsi Monametsi, Samuel Montero, Cecilia L. Moore, Rejoice Mosia, Columbus Moyo, Mumsy Mthethwa, Shepherd Mudzingwa, Tawona Mudzviti, Hilda Mujuru, Emmanuel Mujyambere, Trust Mukanganiki, Cynthia Mukisa Williams, Mark Mulder, Disan Mulima, Alice Mulindwa, Zivai Mupambireyi, Alba Murciano Cabeza, Herbert Murungi, Dorothy Murungu, Sandra Musarurwa, Victor Musiime, Alex V. Musiime, Maria Musisi, Philippa Musoke, Barbara Musoke Nakirya, Godfrey Musoro, Sharif Musumba, Sobia Mustafa, Shirley Mutsai, Phyllis Mwesigwa Rubondo, Mariam Naabalamba, Immaculate Nagawa, Allemah Naidoo, Shamim Nakabuye, Sarah Nakabuye, Sarah Nakalanzi, Justine Nalubwama, Annet Nalugo, Stella Nalusiba, Clementine Namajja, Sylvia Namanda, Paula Namayanja, Esther Nambi, Rachael Kikabi Namuddu, Stella Namukwaya, Florence Namuli, Josephine Namusanje, Rosemary Namwanje, Anusha Nanan-kanjee, Charity Nankunda, Joanita Nankya Baddokwaya, Maria Nannungi, Winnie Nansamba, Kesdao Nanthapisal, Juliet Nanyonjo, Sathaporn Na-Rajsima, Claire Nasaazi, Helena Nascimento, Eleni Nastouli, Wipaporn Natalie Songtaweesin, Kusum Nathoo, Ian Natuhurira, Rashidah Nazzinda, Thabisa Ncgaba, Milly Ndigendawani, Makhosonke Ndlovu, Georgina Nentsa, Chaiwat Ngampiyaskul, Ntombenhle Ngcobo, Nicole Ngo Giang Huong, Pia Ngwaru, Ruth Nhema, Emily Ninsiima, Gloria Ninsiima, Misheck Nkalo Phiri, Antoni Noguera Julian, Monica Nolan, Thornthun Noppakaorattanamanee, Muzamil Nsibuka Kisekka, Eniola Nsirim, Rashina Nundlal, Rosita Nunes, Lungile Nyantsa, Mandisa Nyati, Sean O'Riordan, Paul Ocitti Labeja, Denis Odoch, Rachel Oguntimehin, Martin Ojok, Geoffrey Onen, Wilma Orange, Pradthana Ounchanum, Benson Ouma, Andreia Padrao, Deborah Pako, Anna Parker, Malgorzata Pasko-Szcech, Reena Patel, Rukchanok Peongjakta, Turian Petpranee, Tasmin Phillips, Jackie Philps, Laura Picault, Sonja Pieterse, Helena Pinheiro, Supawadee Pongprapass, Anton Pozniak, Andrew Prendergast, Luis Prieto Tato, Patcharee Puangmalai, Thanyawee Puthanakit, Modiehi Rakgokong, Helena Ramos, Nastassja Ramsagar, Cornelius Rau, Yoann Riault, Pablo Rojo Conejo, Basiimwa Roy Clark, Eddie Rubanga, Baker Rubinga, Chutima Ruklao, Pattira Runarassamee, Chalermpong Saenjum, Chayakorn Saewtrakool, Yacine Saidi, Talia Sainz Costa, Chutima Saisaengjan, Rebecca Sakwa, Tatiana Sarfati, Noshalaza Sbisi, Dihedile Scheppers, Stephan Schultze-Strasser, Ulf Schulze-Sturm, Karen Scott, Janet Seeley, Robert Serunjogi, Leora Sewnarain, Subashinie Sidhoo, Mercy Shibemba, Delane Shingadia, Sheleika Singh, Wasna Sirirungsi, Sibongile Sithebe, Theresa Smit, Kurt Smith, Marlize Smuts, Moira Spyer, Worathip Sripaoraya, Ussanee Srirompotong, Warunee Srisuk, Mark Ssenyonga, Patamawadee Sudsaard, Praornsuda Sukrakanchana, Pathanee Tearsansern, Carla Teixeira, Kanchana Than-in-at, Thitiwat Thapwai, Yupawan Thaweesombat, Jutarat Thewsoongnoen, Rodolphe Thiébaut, Margaret Thomason, Laura Thrasyvoulou, Khanungnit Thungkham, Judith Tikabibamu, Gloria Tinago, Ketmookda Trairat, Gareth Tudor-Williams, Mercy Tukamushaba, Deogratiuos Tukwasibwe, Julius Tumusiime, Joana Tuna, Rebecca Turner, Arttasid Udomvised, Aasia Vadee, Hesti Van Huyssteen, Nadine Van Looy, Yvonne Vaughan-Gordon, Giulio Vecchia, Richard Vowden, Hylke Waalewijn, Rebecca Wampamba, Steve Welch, Ian Weller, Sibusisiwe Weza, Ian White, Kaja Widuch, Helen Wilkes, Sookpanee Wimonklang, Pacharaporn Yingyong, Zaam Zinda Nakawungu, and Peter Zuidewind
Subjects: Adult, Epidemiology, Pyridones, Anti-HIV Agents, Immunology, HIV Infections, 3-Ring, Piperazines, Heterocyclic Compounds, Virology, Oxazines, Humans, Protease Inhibitors, Child, Preschool, Infant, Newborn, Infant, Bayes Theorem, Viral Load, Newborn, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Infectious Diseases, Child, Preschool, Heterocyclic Compounds, 3-Ring, Treatment Outcome
Abstract: Contains fulltext : 283099.pdf (Publisher’s version ) (Open Access) BACKGROUND: Young children living with HIV have few treatment options. We aimed to assess the efficacy and safety of dolutegravir-based antiretroviral therapy (ART) in children weighing between 3 kg and less than 14 kg. METHODS: ODYSSEY is an open-label, randomised, non-inferiority trial (10% margin) comparing dolutegravir-based ART with standard of care and comprises two cohorts (children weighing ≥14 kg and
Published: 2022

6. Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Author: Anna Turkova, Hylke Waalewijn, Man K Chan, Pauline D J Bollen, Mutsa F Bwakura-Dangarembizi, Adeodata R Kekitiinwa, Mark F Cotton, Abbas Lugemwa, Ebrahim Variava, Grace Miriam Ahimbisibwe, Ussanee Srirompotong, Vivian Mumbiro, Pauline Amuge, Peter Zuidewind, Shabinah Ali, Cissy M Kityo, Moherndran Archary, Rashida A Ferrand, Avy Violari, Diana M Gibb, David M Burger, Deborah Ford, Angela Colbers, Amina Farhana Mehar (nee Abdulla), Pattamukkil Abraham, Elaine Abrams, Judith Acero, Gerald Muzorah Agaba, Grace Ahimbisibwe, Barbara Ainebyoona, Winnie Akobye, Yasmeen Akhalwaya, Nazim Akoojee, Shabinah S. Ali, Catherine Andrea, Maria Angeles Muñoz Fernandez, Rogers Ankunda, Diana Antonia Rutebarika, Suvaporn Anugulruengkitt, Tsitsi Apollo, Ronelle Arendze, Juliet Ategeka, Eunice Atim, Lorna Atwine, Abdel Babiker, Sarah Babirye, Enock Babu, Edward Bagirigomwa, Angella Baita, David Balamusani, Patsy Baliram, David Baliruno, Colin Ball, Henry Balwa, Alasdair Bamford, Srini Bandi, Dominique Barker, Linda Barlow-Mosha, Dickson Bbuye, Shazia Begum, Osee Behuhuma, Sarah Bernays, Rogers Besigye, Maria Bester, Joyline Bhiri, Davide Bilardi, Kristien Bird, Pauline Bollen, Chiara Borg, Anne-Marie Borges Da Silva, Jackie Brown, Elena Bruno, Torsak Bunupuradah, David Burger, Nomzamo Buthelezi, Mutsa Bwakura-Dangarembizi, Africanus Byaruhanga, Joanna Calvert, Petronelle Casey, Haseena Cassim, Sphiwee Cebekhulu, Sanuphong Chailert, Suwalai Chalermpantmetagul, Wanna Chamjamrat, Man Chan, Precious Chandiwana, Thannapat Chankun, Sararut Chanthaburanun, Nuttawut Chanto, Ennie Chidziva, Minenhle Chikowore, Joy Chimanzi, Dujrudee Chinwong, Stuart Chitongo, Moses Chitsamatanga, Joshua Choga, Duangrat Chutima, Polly Clayden, Alexandra Coelho, Alexandra Compagnucci, Ana Constança Mendes, Magda Conway, Mark F. Cotton, Jane Crawley, Tim R. Cressey, Jacky Crisp, Ana Cristina Matos, Sumaya Dadan, Jacqui Daglish, Siva Danaviah, Tseleng Daniel, Anita De Rossi, Sukanda Denjanta, Els Dobbels, Maria Dowie, Prosper Dube, Benedictor Dube, Nimisha Dudakia, Alice Elwana, Cristina Epalza, David Eram, Juan Erasmus, Peter Erim, Luis Escosa Garcia, Zaakirah Essack, Carolina Estepa, Monica Etima, Alexandre Fernandes, Maite Fernandez, Felicity Fitzgerald, Jacquie Flynn, Claudia Fortuny Guasch, Caroline Foster, George Fourie, Yolandie Fourie, Sophie Foxall, Derusha Frank, Kate Gandhi, India Garcia, Kathleen Gartner, Joshua Gasa, Gugu Gasa, Carlo Giaquinto, Diana M. Gibb, Coral Gomez Rico, Daniel Gomez-Pena, Secrecy Gondo, Anna Goodman, Maria Gorreti Nakalema, Winnie Gozhora, Pisut Greetanukroh, Biobanco Gregorio Maranon, Tiziana Grossele, Shamiso Gwande, Tapiwa Gwaze, Tsitsi Gwenzi, James Hakim, Emmanuel Hakiza, Abdul Hamid Kaka, Ashley Harley, Mornay Isaacs, Richard Isabirye, Wilber Ishemunyoro, Tom Jacobs, Lungile Jafta, Nasir Jamil, Anita Janse Janse van Rensburg, Vinesh Jeaven, Maria José Mellado Peña, Gonzague Jourdain, Katabalwa Juliet, Thidarat Jumpimai, Raungwit Junkaew, Thidarat Jupimai, Winfred Kaahwa, Mildred Kabasonga, Olivia Kaboggoza, Rose Jacqueline Kadhuba, Ampika Kaewbundit, Kanyanee Kaewmamueng, Bosco Kafufu, Brenda Kakayi, Phakamas Kamboua, Suparat Kanjanavanit, Gladys Kasangaki, Naruporn Kasipong, Miriam Kasozi, Hajira Kataike, Chrispus Katemba, Elizabeth Kaudha, Nkata Kekane, Adeodata R. Kekitiinwa, Edridah Keminyeto, Woottichai Khamduang, Warunee Khamjakkaew, Jiraporn Khamkon, Sasipass Khannak, Orapin Khatngam, Tassawan Khayanchoomnoom, Busi Khumalo, Mirriam Khunene, Suwimon Khusuwan, Phionah Kibalama, Robinah Kibenge, Anthony Kirabira, Cissy M. Kityo, Lameck Kiyimba, Nigel Klein, Soraya Klinprung, Robin Kobbe, Olivia Kobusingye, Josephine Kobusungye, Areerat Kongponoi, Christoph Königs, Olivier Koole, Christelle Kouakam, Nitinart Krueduangkam, Namthip Kruenual, Nuananong Kunjaroenrut, Raymonds Kyambadde, Priscilla Kyobutungi, Flavia Kyomuhendo, Erinah Kyomukama, Reshma Lakha, Cleopatra Langa, Laddawan Laomanit, Emily Lebotsa, Prattana Leenasirimakul, Lawrence Lekku, Sarah Lensen, Valériane Leroy, Jin Li, Afaaf Liberty, Juthamas Limplertjareanwanich, Emma Little, Ezra Lutalo, Jose Luis Jimenez, Hermione Lyall, Candice MacDonald, Gladness Machache, Penelope Madlala, Tryphina Madonsela, Nomfundo Maduna, Joel Maena, Apicha Mahanontharit, Collin Makanga, Candice Makola, Shafic Makumbi, Lucille Malgraaf, Angelous Mamiane, Felicia Mantkowski, Wendy Mapfumo, Laura Marques, Agnes Mary Mugagga, Lindiwe Maseko, Tshepiso Masienyane, Ruth Mathiba, Farai Matimba, Sajeeda Mawlana, Emmanuel Mayanja, Fatima Mayat, Ritah Mbabazi, Nokuthula Mbadaliga, Faith Mbasani, Kathleen McClaughlin, Helen McIlleron, Watchara Meethaisong, Patricia Mendez Garcia, Annet Miwanda, Carlota Miranda, Siphiwe Mkhize, Kgosimang Mmolawa, Rosie Mngqibisa, Fatima Mohamed, Tumelo Moloantoa, Maletsatsi Monametsi, Samuel Montero, Cecilia L. Moore, Rejoice Mosia, Columbus Moyo, Mumsy Mthethwa, Shepherd Mudzingwa, Tawona Mudzviti, Hilda Mujuru, Emmanuel Mujyambere, Trust Mukanganiki, Cynthia Mukisa Williams, Mark Mulder, Disan Mulima, Alice Mulindwa, Zivai Mupambireyi, Alba Murciano Cabeza, Herbert Murungi, Dorothy Murungu, Sandra Musarurwa, Victor Musiime, Alex V. Musiime, Maria Musisi, Philippa Musoke, Barbara Musoke Nakirya, Godfrey Musoro, Sharif Musumba, Sobia Mustafa, Shirley Mutsai, Phyllis Mwesigwa Rubondo, Mariam Naabalamba, Immaculate Nagawa, Allemah Naidoo, Shamim Nakabuye, Sarah Nakabuye, Sarah Nakalanzi, Justine Nalubwama, Annet Nalugo, Stella Nalusiba, Clementine Namajja, Sylvia Namanda, Paula Namayanja, Esther Nambi, Rachael Kikabi Namuddu, Stella Namukwaya, Florence Namuli, Josephine Namusanje, Rosemary Namwanje, Anusha Nanan-kanjee, Annet Nanduudu, Charity Nankunda, Joanita Nankya Baddokwaya, Maria Nannungi, Winnie Nansamba, Kesdao Nanthapisal, Juliet Nanyonjo, Sathaporn Na-Rajsima, Claire Nasaazi, Helena Nascimento, Eleni Nastouli, Wipaporn Natalie Songtaweesin, Kusum Nathoo, Ian Natuhurira, Rashidah Nazzinda, Thabisa Ncgaba, Milly Ndigendawani, Makhosonke Ndlovu, Georgina Nentsa, Chaiwat Ngampiyaskul, Ntombenhle Ngcobo, Nicole Ngo Giang Huong, Pia Ngwaru, Ruth Nhema, Emily Ninsiima, Gloria Ninsiima, Misheck Nkalo Phiri, Antoni Noguera Julian, Monica Nolan, Thornthun Noppakaorattanamanee, Muzamil Nsibuka Kisekka, Eniola Nsirim, Rashina Nundlal, Rosita Nunes, Lungile Nyantsa, Mandisa Nyati, Sean O'Riordan, Paul Ocitti Labeja, Denis Odoch, Rachel Oguntimehin, Martin Ojok, Geoffrey Onen, Wilma Orange, Pradthana Ounchanum, Benson Ouma, Andreia Padrao, Deborah Pako, Anna Parker, Malgorzata Pasko-Szcech, Reena Patel, Rukchanok Peongjakta, Turian Petpranee, Tasmin Phillips, Jackie Philps, Laura Picault, Sonja Pieterse, Helena Pinheiro, Supawadee Pongprapass, Anton Pozniak, Andrew Prendergast, Luis Prieto Tato, Patcharee Puangmalai, Thanyawee Puthanakit, Modiehi Rakgokong, Helena Ramos, Nastassja Ramsagar, Cornelius Rau, Yoann Riault, Pablo Rojo Conejo, Basiimwa Roy Clark, Eddie Rubanga, Baker Rubinga, Chutima Ruklao, Pattira Runarassamee, Chalermpong Saenjum, Chayakorn Saewtrakool, Yacine Saidi, Talia Sainz Costa, Chutima Saisaengjan, Rebecca Sakwa, Tatiana Sarfati, Noshalaza Sbisi, Dihedile Scheppers, Stephan Schultze-Strasser, Ulf Schulze-Sturm, Karen Scott, Janet Seeley, Robert Serunjogi, Leora Sewnarain, Clare Shakeshaft, Subashinie Sidhoo, Mercy Shibemba, Delane Shingadia, Sheleika Singh, Wasna Sirirungsi, Sibongile Sithebe, Theresa Smit, Kurt Smith, Marlize Smuts, Moira Spyer, Worathip Sripaoraya, Warunee Srisuk, Mark Ssenyonga, Patamawadee Sudsaard, Praornsuda Sukrakanchana, Pathanee Tearsansern, Carla Teixeira, Kanchana Than-in-at, Thitiwat Thapwai, Yupawan Thaweesombat, Jutarat Thewsoongnoen, Rodolphe Thiébaut, Margaret Thomason, Laura Thrasyvoulou, Khanungnit Thungkham, Judith Tikabibamu, Gloria Tinago, Ketmookda Trairat, Gareth Tudor-Williams, Mercy Tukamushaba, Deogratiuos Tukwasibwe, Julius Tumusiime, Joana Tuna, Rebecca Turner, Arttasid Udomvised, Aasia Vadee, Hesti Van Huyssteen, Nadine Van Looy, Yvonne Vaughan-Gordon, Giulio Vecchia, Richard Vowden, Rebecca Wampamba, Steve Welch, Ian Weller, Sibusisiwe Weza, Ellen White, Ian White, Kaja Widuch, Helen Wilkes, Sookpanee Wimonklang, Ben Wynne, Pacharaporn Yingyong, and Zaam Zinda Nakawungu
Subjects: Male, Adolescent, Pyridones, Epidemiology, Immunology, Infant, HIV Infections, 3-Ring, Piperazines, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Infectious Diseases, Child, Child, Preschool, Female, Heterocyclic Compounds, 3-Ring, Humans, Oxazines, Rifampin, Uganda, HIV-1, Tuberculosis, Heterocyclic Compounds, Virology, Preschool
Abstract: Contains fulltext : 282959.pdf (Publisher’s version ) (Open Access) BACKGROUND: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. METHODS: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to
Published: 2022

7. ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing

Author: Clare Shakeshaft, Carlo Giaquinto, Tim R. Cressey, Adeodata Kekitiinwa, David M. Burger, Pauline Amuge, Pablo Rojo, Cecilia L. Moore, Osee Behuhuma, Yacine Saϊdi, Linda Barlow-Mosha, James Hakim, Alexandra Compagnucci, Lorna Atwine, Diana M. Gibb, Ebrahim Variava, Hilda Mujuru, Mark F. Cotton, Victor Musiime, Moherndran Archary, Deborah Ford, Cissy Kityo, Thanyawee Puthanakit, Anna Turkova, Avy Violari, Abbas Lugemwa, Medical Research Council Clinical Trials Unit (MRC CTU), University College of London [London] (UCL), University of Zimbabwe (UZ), Baylor College of Medicine Children's Foundation [Kampala, Uganda] (BCMCF), Joint Clinical Research Centre, MUJHU Research Collaboration [Kampala, Uganda] (MUJHURC), Chiang Mai University (CMU), Harvard T.H. Chan School of Public Health, University of Liverpool, Perinatal HIV Research Unit [Johannesburg, South Africa] (PHRU), University of the Witwatersrand [Johannesburg] (WITS), Klerksdorp Tshepong Hospital Complex [Matlosana, South Africa] (KTHC), Family Center for Research with Ubuntu [Cape Town, South Africa] (FCRU), Durban International Clinical Research Site [Durban, South Africa] (DICRS), Essais Thérapeutiques et Maladies Infectieuses, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chulalongkorn University [Bangkok], Africa Health Research Institute [Hlabisa, South Africa] (AHRI), Hlabisa Hospital [Hlabisa, South Africa] (HH), Radboud University Medical Center [Nijmegen], Università degli Studi di Padova = University of Padua (Unipd), Hospital Universitario 12 de Octubre [Madrid], ODYSSEY Trial Team: Shabinah Ali, Abdel Babiker, Chiara Borg, Anne-Marie Borges Da Silva, Joanna Calvert, Deborah Ford, Joshua Gasa, Diana M Gibb, Nasir Jamil, Sarah Lensen, Emma Little, Fatima Mohamed, Samuel Montero, Cecilia L Moore, Rachel Oguntimehin, Anna Parker, Reena Patel, Tasmin Phillips, Tatiana Sarfati, Karen Scott, Clare Shakeshaft, Moira Spyer, Margaret Thomason, Anna Turkova, Rebecca Turner, Nadine Van Looy, Ellen White, Kaya Widuch, Helen Wilkes, Ben Wynne, Carlo Giaquinto, Tiziana Grossele, Daniel Gomez-Pena, Davide Bilardi, Giulio Vecchia, Alexandra Compagnucci, Yacine Saidi, Yoann Riault, Alexandra Coelho, Laura Picault, Christelle Kouakam, Tim R Cressey, Suwalai Chalermpantmetagul, Dujrudee Chinwong, Gonzague Jourdain, Rukchanok Peongjakta, Pra-Ornsuda Sukrakanchana, Wasna Sirirungsi, Janet Seeley, Sarah Bernays, Magda Conway, Nigel Klein, Eleni Nastouli, Anita De Rossi, Maria Angeles Munoz Fernandez, David Burger, Pauline Bollen, Angela Colbers, Hylke Waalewijn, Cissy M Kityo, Victor Musiime, Elizabeth Kaudha, Annet Nanduudu, Emmanuel Mujyambere, Paul Ocitti Labeja, Charity Nankunda, Juliet Ategeka, Peter Erim, Collin Makanga, Esther Nambi, Abbas Lugemwa, Lorna Atwine, Edridah Keminyeto, Deogratiuos Tukwasibwe, Shafic Makumbi, Emily Ninsiima, Mercy Tukamushaba, Rogers Ankunda, Ian Natuhurira, Miriam Kasozi, Baker Rubinga, Adeodata R Kekitiinwa, Pauline Amuge, Dickson Bbuye, Justine Nalubwama, Winnie Akobye, Muzamil Nsibuka Kisekka, Anthony Kirabira, Gloria Ninsiima, Sylvia Namanda, Gerald Agaba, Immaculate Nagawa, Annet Nalugo, Florence Namuli, Rose Kadhuba, Rachael Namuddu, Lameck Kiyimba, Angella Baita, Eunice Atim, Olivia Kobusingye, Clementine Namajja, Africanus Byaruhanga, Rogers Besigye, Herbert Murungi, Geoffrey Onen, Philippa Musoke, Linda Barlow-Mosha, Grace Ahimbisibwe, Rose Namwanje, Monica Etima, Mark Ssenyonga, Robert Serunjogi, Hajira Kataike, Richard Isabirye, David Balamusani, Monica Nolan, Mark F Cotton, Anita Janese van Rensburg, Marlize Smuts, Catherine Andrea, Sumaya Dadan Sonja Pieterse, Vinesh Jaeven, Candice Makola, George Fourie, Kurt Smith, Els Dobbels, Peter Zuidewind, Hesti Van Huyssteen, Mornay Isaacs, Georgina Nentsa, Thabis Ncgaba, Candice MacDonald, Mandisa Mtshagi, Maria Bester, Wilma Orange, Ronelle Arendze, Mark Mulder, George Fourie, Avy Violari, Nastassja Ramsagar, Afaaf Liberty, Ruth Mathiba, Lindiwe Maseko, Nakata Kekane, Busi Khumlo, Mirriam Khunene, Noshalaza Sbisi, Jackie Brown, Ryphina Madonsela, Nokuthula Mbadaliga, Zaakirah Essack, Reshma Lakha, Aasia Vadee, Derusha Frank, Nazim Akoojee, Maletsatsi Monametsi, Gladness Machache, Yolandie Fourie, Anusha Nanan-Kanjee, Juan Erasmus, Angelous Mamiane, Tseleng Daniel, Fatima Mayat, Nomfundo Maduna, Patsy Baliram, Chaiwat Ngampiyasakul, Pisut Greetanukroh, Wanna Chamjamrat, Praechadaporn Khannak, Pornchai Techakunakorn, Thitiwat Thapwai, Patcharee Puangmalai, Ampai Maneekaew, Pradthana Ounchanum, Yupawan Thaweesombat, Areerat Kongponoi, Jutarat Thewsoongnoen, Suparat Kanjanavanit, Pacharaporn Yingyong, Thida Namwong, Rangwit Junkaew, Ussanee Srirompotong, Patamawadee Sudsaard, Siripun Nuanbuddee, Sookpanee Wimonklang, Sathaporn Na-Rajsima, Suchart Thongpaen, Pattira Runarassamee, Watchara Meethaisong, Arttasid Udomvised, Ebrahim Variava, Modiehi Rakgokong, Dihedile Scheppers, Tumelo Moloantoa, Abdul Hamid Kaka, Tshepiso Masienyane, Akshmi Ori, Kgosimang Mmolawa, Pattamukkil Abraham, Moherndran Archary, Rejoice Mosia, Sajeeda Mawlana, Rosie Mngqibisa, Rashina Nundlal, Elishka Singh, Penelope Madlala, Allemah Naidoo, Sphiwee Cebekhulu, Petronelle Casey, Collin Pillay, Subashinie Sidhoo, Minenhle Chikowore, Lungile Nyantsa, Melisha Nunkoo, Terence Nair, Enbavani Pillay, Sheleika Singh, Sheroma Rajkumar, Osee Behuhuma, Olivier Koole, Kristien Bird, Nomzamo Buthelezi, Mumsy Mthethwa, James Hakim, Hilda Mujuru, Kusum Nathoo, Mutsa Bwakura-Dangarembizi, Ennie Chidziva, Shepherd Mudzingwa, Themelihle Bafana, Colin Warambwa, Godfrey Musoro, Gloria Tinago, Shirley Mutsai, Columbus Moyo, Ruth Nhema, Misheck Nkalo Phiri, Stuart Chitongo, Joshua Choga, Joyline Bhiri, Wilber Ishemunyoro, Makhosonke Ndlovu, Thanyawee Puthanakit, Naruporn Kasipong, Sararut Chanthaburanun, Kesdao Nanthapisal, Thidarat Jupimai, Thornthun Noppakaorattanamanee, Torsak Bunupuradah, Wipaporn Natalie Songtaweesin, Chutima Saisaengjan, Stephan Schultze-Straber, Christoph Konigs, Robin Kobbe, Felicia Mantkowski, Steve Welch, Jacqui Daglish, Laura Thrasyvoulou, Delane Singadia, Sophie Foxall, Judith Acero, Gosia Pasko-Szcech, Jacquie Flynn, Gareth Tudor-Williams, Farhana Abdulla, Srini Bandi, Jin Li, Sean O'Riordan, Dominique Barker, Richard Vowden, Colin Ball Eniola Nsirim, Kathleen McClughlin, India Garcia, Pablo Rojo Conejo, Cristina Epalza, Luis Prieto Tato, Maite Fernandez, Luis Escosa Garcia, Maria José Mellado Peña, Talia Sainz Costa, Claudia Fortuny Guasch, Antoni Noguera Julian, Carolina Estepa, Elena Bruno, Alba Murciano Cabeza, Maria Angeles Muñoz Fernandez, Paula Palau, Laura Marques, Carla Teixeira, Alexandre Fernandes, Rosita Nunes, Helena Nascimento, Andreia Padrao, Joana Tuna, Helena Ramos, Ana Constança Mendes, Helena Pinheiro, Ana Cristina Matos, Flavia Kyomuhendo, Sarah Nakalanzi, Cynthia Mukisa Williams, Ntombenhle Ngcobo, Deborah Pako, Jacky Crisp, Benedictor Dube, Precious Chandiwana, Winnie Gozhora, Ian Weller, Elaine Abrams, Tsitsi Apollo, Polly Clayden, Valériane Leroy, Anton Pozniak, Jane Crawley, Rodolphe Thiébaut, Helen McIlleron, Alasdair Bamford, Hermione Lyall, Andrew Prendergast, Felicity Fitzgerald, Anna Goodman, Malbec, Odile, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Radboud University Medical Centre [Nijmegen, The Netherlands], and Universita degli Studi di Padova
Subjects: 0301 basic medicine, Male, Pediatrics, [SDV]Life Sciences [q-bio], HIV Infections, Basket trial, Dolutegravir, Efficacy, HIV, Paediatric, Pharmacokinetic, Randomized control trial, Safety, Adolescent, Body Weight, Child, Child, Preschool, Cohort Studies, Drug Dosage Calculations, Europe, Female, HIV Integrase Inhibitors, HIV-1, Heterocyclic Compounds, 3-Ring, Humans, Oxazines, Piperazines, Pyridones, RNA, Viral, South Africa, Thailand, Treatment Outcome, Uganda, Viral Load, World Health Organization, Zimbabwe, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, Heterocyclic Compounds, law, Clinical endpoint, Medicine, Viral, 030212 general & internal medicine, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, Viral load, Cohort study, Research Article, medicine.medical_specialty, 030106 microbiology, 3-Ring, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, lcsh:RC109-216, Dosing, Preschool, Pregnancy, business.industry, Clinical study design, medicine.disease, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], chemistry, RNA, business
Abstract: Background Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested pharmacokinetic (PK) sub-studies which evaluated pragmatic World Health Organization (WHO) weight-band-based DTG dosing and opened recruitment to children Methods ODYSSEY (Once-daily DTG based ART in Young people vS. Standard thErapY) is an open-label, randomised, non-inferiority, basket trial comparing the efficacy and safety of DTG + 2 nucleos(t) ides (NRTIs) versus standard-of-care (SOC) in HIV-infected children Results Between September 2016 and June 2018, 707 children weighing ≥14 kg were enrolled; including 311 ART-naïve children and 396 children starting second-line. 47% of children were enrolled in Uganda, 21% Zimbabwe, 20% South Africa, 9% Thailand, 4% Europe. 362 (51%) participants were male; median age [range] at enrolment was 12.2 years [2.9–18.0]. 82 (12%) children weighed 14 to Conclusions By employing a basket design, to include ART-naïve and -experienced children, and nested PK sub-studies, the ODYSSEY trial efficiently evaluates multiple scientific questions regarding dosing and effectiveness of DTG-based ART in children. Trial registration NCT, NCT02259127, registered 7th October 2014; EUDRACT, 2014–002632-14, registered 18th June 2014 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002632-14/ES); ISRCTN, ISRCTN91737921, registered 4th October 2014.
Published: 2021

8. Long-term clinical, virological and immunological outcomes following planned treatment interruption in HIV-infected children

Author: Nigel Klein, Carlo Giaquinto, Lynda Harper, Tim R. Cressey, Alexandra Compagnucci, Yoann Riault, Annalisa Dalzini, Deborah Ford, Marisa Zanchetta, Yacine Saidi, Riccardo Freguja, A. De Rossi, P. Del Bianco, DM Gibb, and Alasdair Bamford
Subjects: 0301 basic medicine, CD4-Positive T-Lymphocytes, medicine.medical_specialty, Adverse outcomes, Human immunodeficiency virus (HIV), HIV Infections, CD8-Positive T-Lymphocytes, medicine.disease_cause, immunology, 03 medical and health sciences, 0302 clinical medicine, Immunophenotyping, children, Pulmonary tuberculosis, Hiv infected, Internal medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Stage (cooking), Child, Randomized Controlled Trials as Topic, Original Research, business.industry, Health Policy, treatment interruption, HIV, Viral Load, 030112 virology, Antiretroviral therapy, CD4 Lymphocyte Count, virology, Infectious Diseases, Treatment Outcome, Treatment interruption, ARV, business
Abstract: OBJECTIVES Planned treatment interruption (PTI) of antiretroviral therapy (ART) in adults is associated with adverse outcomes. The PENTA 11 trial randomized HIV-infected children to continuous ART (CT) vs. CD4-driven PTIs. We report 5 years' follow-up after the end of main trial. METHODS Post-trial, all children resumed ART. Clinical, immunological, virological and treatment data were collected annually. A sub-study investigated more detailed immunophenotype. CT and PTI arms were compared using intention-to-treat. Laboratory parameters were compared using linear regression, adjusting for baseline values; mixed models were used to include all data over time. RESULTS In all, 101 children (51 CT, 50 PTI) contributed a median of 7.6 years, including 5.1 years of post-trial follow-up. Post-trial, there were no deaths, one pulmonary tuberculosis and no other CDC stage B/C events. At 5 years post-trial, 90% of children in the CT vs. 82% in the PTI arm had HIV RNA
Published: 2019

9. The EPIICAL project: an emerging global collaboration to investigate immunotherapeutic strategies in HIV-infected children

Author: Eleni Nastouli, Carlo Giaquinto, Paolo Palma, Nadia Mora, Katherine Luzuriaga, William Borkowsky, Caroline Foster, A. De Rossi, Andrew J. Yates, Jintanat Ananworanich, Britta Wahren, Paola Zangari, Nicola Cotugno, Savita Pahwa, Pablo Rojo, Paolo Rossi, María Ángeles Muñoz-Fernández, Stefania Bernardi, Vincent Calvez, Alexandra Compagnucci, Nigel Klein, Emma Concetta Manno, Diana M. Gibb, and Deenan Pillay
Subjects: medicine.medical_specialty, Epidemiology, Immunology, Human immunodeficiency virus (HIV), Reviews, Bioinformatics, medicine.disease_cause, Microbiology, children, Virology, Hiv infected, Medicine, Intensive care medicine, business.industry, Public Health, Environmental and Occupational Health, therapeutic vaccines, HIV, immunotherapies, Early infancy, Antiretroviral therapy, QR1-502, Infectious Diseases, Treatment interruption, Therapeutic vaccine, early treated, Public aspects of medicine, RA1-1270, business
Abstract: Short summary: The EPIICAL (Early-treated Perinatally HIV-infected Individuals: Improving Children's Actual Life with Novel Immunotherapeutic Strategies) project arises from the firm belief that perinatally infected children treated with suppressive antiretroviral therapy (ART) from early infancy represent the optimal population model in which to study novel immunotherapeutic strategies aimed at achieving ART-free remission. This is because HIV-infected infants treated within 2–3 months of life have a much reduced viral reservoir size, and rarely show HIV-specific immunity but preserve normal immune development. The goal of EPIICAL is the establishment of an international collaboration to develop a predictive platform using this model to select promising HIV therapeutic vaccine candidates, leading to prioritisation or deprioritisation of novel immunotherapeutic strategies.To establish this platform, the EPIICAL Consortium aims to: develop predictive models of virological and immunological dynamics associated with response to early ART and to treatment interruption using available data from existing cohorts/studies of early-treated perinatally HIV-infected children; optimise methodologies to better characterise immunological, virological and genomic correlates/profiles associated with viral control; test novel immunotherapeutic strategies using in vivo proof-of-concept (PoC) studies with the aim of inducing virological, immunological and transcriptomic correlates/profiles equivalent to those defined by the predictive model. This approach will strengthen the capacity for discovery, development and initial testing of new therapeutic vaccine strategies through the integrated efforts of leading international scientific groups, with the aim of improving the health of HIV-infected individuals.
Published: 2015

10. Hepatic, Renal, Hematologic, and Inflammatory Markers in HIV-Infected Children on Long-term Suppressive Antiretroviral Therapy

Author: Anna Turkova, Pactg, Anrs Study Team, Alexandra Compagnucci, Gareth Tudor-Williams, Yacine Saidi, Linda Harrison, Penpact (Penta ), Meredith G. Warshaw, and Ann J. Melvin
Subjects: 0301 basic medicine, Cyclopropanes, Male, Time Factors, Lipopolysaccharide Receptors, HIV Infections, Kidney, Gastroenterology, Lopinavir, chemistry.chemical_compound, 0302 clinical medicine, Interquartile range, Antiretroviral Therapy, Highly Active, 030212 general & internal medicine, Child, biology, virus diseases, General Medicine, Europe, Infectious Diseases, C-Reactive Protein, Cholesterol, Treatment Outcome, Liver, Alkynes, Child, Preschool, Creatinine, Toxicity, Reverse Transcriptase Inhibitors, Female, Drug Monitoring, medicine.drug, medicine.medical_specialty, Efavirenz, Adolescent, Anti-HIV Agents, 030106 microbiology, Electronic Articles, Fibrin Fibrinogen Degradation Products, 03 medical and health sciences, Internal medicine, medicine, Humans, Cystatin C, Inflammation, Ritonavir, business.industry, Interleukin-6, C-reactive protein, Benzoxazines, chemistry, Pediatrics, Perinatology and Child Health, North America, biology.protein, business, Biomarkers
Abstract: Background Data on long-term toxicity of antiretroviral therapy (ART) in HIV-infected children are sparse. PENPACT-1 was an open-label trial in which HIV-infected children were assigned randomly to receive protease inhibitor (PI)- or nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based ART. Methods We examined changes in clinical, immunologic, and inflammatory markers from baseline to year 4 in the subset of children in the PENPACT-1 study who experienced viral suppression between week 24 and year 4 of ART. Liver enzyme, creatinine, and cholesterol levels and hematologic parameters were assessed during the trial. Cystatin C, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), d-dimer, and soluble CD14 (sCD14) were assayed from cryopreserved specimens. Results Ninety-nine children (52 on PI-based and 47 on NNRTI-based ART) met inclusion criteria. The median age at initiation of ART was 6.5 years (interquartile range [IQR], 3.7-13.4 years), and 22% were aged
Published: 2017

11. First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, randomised phase 2/3 trial

Author: J. Fanning, M. Keuth, E. Cagwin, E. Lachassinne, S. Campbell, K. Jeffries, J. Tutko, L. Vladau, Raffaele Badolato, Paolo Palma, J. Orendi, I. Colombo, A. Buckton, J. Neubert, Y. Rodriguez Lozano, V. Novelli, E. Belfrage, M. della Negra, N. Boudjoudi, R. Nickel, F. Schumacher, A. Furcas, J. Navarra, C. B. S. de Souza, B. Zöhrer, M. Neely, G. Pontrelli, D. Duiculescu, M. Clapson, K. A. Contello, G. Kudesia, R. Santos, Catherine Dollfus, Raffaella Rosso, G. Lewis, A. Sarah Walker, James Homans, Pier-Angelo Tovo, T. Chen, K. Fidler, V. Reliquet, A. Aali, J. Cottalorda, D. Michalik, Barbra Murante, Marisa Zanchetta, Jaime G. Deville, P. McNeil, Z. Shah, K. O’connor, H. Haley, M. I. Gonzalez Tomé, M. C. Cervi, Rosa Bologna, Abdel Babiker, D. Hamadache, A. Pala, Merlin L. Robb, E. Voicu, Cristina Bertulli, A. Smyth, G. Hadjou, L. Lugo, M. Burke, E. Hayes, Janice Hodge, Marco Tabone, Ram Yogev, A. Jurgrau, Lucia de Araujo Evangelista, K. Nguyen, P. Kamara, N. Le Gueyades, D. Picard, A. Dehée, J. Leleu, D. M. Ferraro, F. Damond, Iraina Fernandes, S. Bradford, K. Swaby, Laura Schneider, Albert Faye, T. Dunaway, Carlo Giaquinto, D. Otelea, C. Jennings, D. Gibb, J. Horton, G. Alexandre-Castor, D. Muir, A. Mazzei, J. Nelson, M. Snelling, M.J. Mellado Peña, S. Welch, C. Belmega, B. V.M. Negrini, L. Garrovillo, S. Walters, C. Müller, Andrew Collinson, Lynda Harper, T. Fleming, C. Concato, Polly Clayden, K. Elkins, A. Schnuriger, I. Farias, Caroline Foster, M. C. Sapia, L. Alecsandru, A. Alvarez, A. Waters, N. O’sullivan, S. Buskirk, Yacine Saidi, R. Pineiro Perez, Elaine J. Abrams, Y. C. Lian, L. Buck, H. Tchidjou, M. Gonzalez, S. Blanche, M. E. Paul, Leonard B. Weiner, K. Moshal, S. Marino, S. Wong, Angela Berzi, D. P. Pacola, A. Rodallec, C. Frillici, C. Rodriguez, Cristiana Oprea, L. Dehache, Anthony C. Gordon, Christine Rouzioux, P. Valentin, Jay A. Levy, Sharon Nachman, Andrea Kovacs, J. Batra, R. Croteau, I. L. Febo, Yvonne J. Bryson, P. Archer, Z. Benabadji, M. Stevanovic, E. Hutchison, G. Boddy, M. Ilie, K. Kabat, C. Monrose, Vania Giacomet, Marianne C. Jacobsen, Antonio Mazza, N. Patel, C. Farmer, A. Krivine, I. Fineanganofo, M. García López, C. Graisbery, CS Peckham, F. Monpoux, William Borkowsky, M. Denon, A. Doyle, T. Schmitz, Ann J. Melvin, Gareth Tudor-Williams, Osvalda Rampon, L. Marty, M. Sellier, M. Fernandez, Marc Foca, C. Hayes, C. Peiser, T. C. Matsubara, A. Finn, P. Martín Fontelos, W. A. Holz, A. Zoccano, Mike Sharland, R. Dersimonian, S. Champion, M. Kline, D. Collins, J.T. Ramos Amador, Angela Di Martino, Hermione Lyall, Christine A. Powell, Stephen A. Spector, J. Swan, S. Eloby-Childress, S. Yeadon, C. McMullen-Jackson, A. L. Chang, Diana M. Gibb, Henriette J. Scherpbier, G. Ball, Hannah Castro, Elena Spinelli, M. Jervis, G. Delommois, S. Scott, I. Garcia Mellado, S. Discenza, P. Lepage, S. Hawkins, F. Méchinaud, Alexandra Compagnucci, T. Ilmet, A. Mangano, H. Carreira, Andrew J. Pollard, G. Silva, L. Cerracchio, R. Sellers, Edward Handelsman, C. Floch, M. Lajeunesse, Stefano Vella, Thalita F. Abreu, N. Martinez-Allier, C. Florea, C. Newbould, I. Grosch-Wörner, M. F. Courcoux, Gert Warncke, I. Whyms, J. C. Gabaldi, T. Piening, F. Hoffman, V. Shah, B. Bucholz, S. Costa, G. Firtion, E. R. Stiehm, J. Palm, S. Deygoo, L. Rosado, V. Tournier, Y. Saïdi, M. Wigger, G. Vaudre, V. Lobato, E. Yeagley, A. B. Bohlin, Delane Shingadia, L. S. Spencer, M. Depala, G. Tardei, S. Akleh, S. Marks, S. Vasquez Bonilla, Stefania Bernardi, D. Costello, S. Segal, S. Gudowius, Saniyyah Mahmoudi, M. Debré, C. Borne, D. Melvin, S. Kaye, S. Johnson, Ellen G. Chadwick, Marie-Laure Chaix, H. Loeffler, G. Stringari, J. L. Jimenez, Arry Dieudonne, G. Notheis, J. Dodge, C. Nesel, D. Mecikovsky, Meredith G. Warshaw, Shunmay Yeung, C. De Bortoli, J. Shenton, R. de Groot, S. Forcat, M. A. Kelly, J. Usher, I. Falconi, M. Rein, D. Nayagam, R. Delgado Garcia, P. McMaster, J. Flynn, S. Rugina, Susan A. Fiscus, S. Liebeschuetz, A. Sorlini, G. Tatum, Magdalena Marczyńska, H. J. Laws, Paul Palumbo, Nigel Klein, E. Daghofer, D. Painter, D. Poalelungi, Anne A. Gershon, L. Martins, N. Pineda, Patricia M. Flynn, J. H. Darbyshire, Michael Hughes, Pim Brouwers, Guido Castelli-Gattinara, M. Byrne, J. Stroobant, G. Talero, C. Reed, D. Patel, F. Nganzali, J. F. Méritet, M. Elizabeth Smith, M. A. Muñoz Fernandez, K. Huck, G. Castelli Gattinara, M. L. Issac, S. Gaur, M. Johnson, K. Mohan, B. Ward, A. Cheng, M. Dunn, M. Frere, T. Alford, K. Doerholt, S. Storey, J. Smith, S. Cleto, A. Ferreira, J. Darbyshire, J. Johnson, A. Marion, P. Butler, K. M. Kim, H. Hichou, D. Casey, L. Farrelly, R. Draghicenoiu, Alessandra Viganò, M. F. Melo, S. Bellert, Jintanat Ananworanich, F. Ferreira, K. Sloper, Deenan Pillay, E. Ferguson, Karina Butler, D. Rivaux, A. D. Fernandez, M. Penin, V. Bennato, M. Filisetti, W. Tomosada, Daria Trabattoni, J. P. Aboulker, A. Diniz, Patricia Emmanuel, C. Rodier, Jorge Pinto, S. McDonagy, M. Goode, K. Swaminathan, H. Sprenger, L. Deveikis, L. Ball, E. André, Susan Laverty, John S. Lambert, F. Abaab, C. Hill, A. Menon, A. García Torre, T. Belger, Christoph Rudin, R. Neubauer, Cornelia Feiterna-Sperling, U. Wintergerst, B. Brody, Silvia Netescu, Ross E. McKinney, Yoann Riault, J. Galimand, G. Deluchi, J. Hobbs, K. Buckberry, C. Mazhude, S. Doshi, Maripat Toye, C. Ball, David M. Burger, A. Werthmann, R. Matusa, J. Wong, Joseph A. Church, M. Pourrat, K. Pfurtscheller, S. Seyboldt, R. Lawrence, M. Butler, D. Scott, T. Niehues, Katherine Luzuriaga, B. Pabst, R. Lakshman, M. Donohoe, A. Ortwin, M. Brusati, M. O’connell, W. Queiroz, M. P. Gomez, J. C. Roa, P. Rojo Conejo, A. De Rossi, C. Norgeux, A. Rochford, Linda Harrison, Tao Dong, W. Zenz, S. Donaghy, S. Mellul, L. M. Lira, Paula Britto, J. Romeiro, C. Taylor, J. Jackson Alvarez, Judith A. Guzman-Cottrill, J. Arias, Lynne M. Mofenson, D. Calo, I. Le Moal, J. Lujan-Zimmerman, T. Alchediak, C. Guérin, Ricardo H. Oliveira, Jonathan Cohen, D. Kwolfe, Ana Puga, L. Navarante, William T. Shearer, L. Angeli, Marc Lallemant, J. Bane, Niels Henrik Valerius, Ayesha Mirza, John F. Modlin, G. Rossetti, David Nadal, M. Acevedo-Flores, F. Shackley, S. Léonardo, E. Smidt, I. Jimenez Nacher, Margarita Silio, Geoffrey A. Weinberg, C. Galvez, F. Kakehasi, L. Fabregas, S. Moore, M. M. Mussi-Pinhata, M. O’connor, M. Diniz, M. Mardarescu, J. King, Sohail Rana, D. Johnson, J. M. Ferrari, Lisa M. Frenkel, T. Hastings, C. Wells, R. B. Van Dyke, G. Bowen, Claire Thorne, L. Sen, E. Hyland, L. Barrett, E Jungmann, Mobeen H. Rathore, D. Beniken, B. Sodiende, C. Ryan, A. Malheiro, Y. Peng, R. O’connell, A. Walsh, John L. Sullivan, A. Deveikis, P. Rice, A. Le Pelletier, and A. Poziak
Subjects: Male, medicine.medical_specialty, Nevirapine, Pediatric AIDS, Adolescent, Anti-HIV Agents, antiretroviral therapy, pediatric HIV/AIDS, antiretroviral therapy, HIV Infections, Article, Nucleoside Reverse Transcriptase Inhibitor, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antiretroviral Therapy, Highly Active, medicine, Humans, pediatric HIV/AIDS, Protease inhibitor (pharmacology), 030212 general & internal medicine, Child, 0303 health sciences, Intention-to-treat analysis, Reverse-transcriptase inhibitor, 030306 microbiology, business.industry, Infant, South America, Viral Load, Virology, Settore MED/38, 3. Good health, Europe, Infectious Diseases, Nelfinavir, Treatment Outcome, Child, Preschool, North America, Female, Drug Monitoring, business, Viral load, medicine.drug
Abstract: Background Children with HIV will be on antiretroviral therapy (ART) longer than adults, and therefore the durability of first-line ART and timing of switch to second-line are key questions. We assess the long-term outcome of protease inhibitor and non-nucleoside reverse transcriptase inhibitor (NNRTI) first-line ART and viral load switch criteria in children. Methods In a randomised open-label factorial trial, we compared effectiveness of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor versus two NRTIs plus an NNRTI and of switch to second-line ART at a viral load of 1000 copies per mL versus 30,000 copies per mL in previously untreated children infected with HIV from Europe and North and South America. Random assignment was by computer-generated sequentially numbered lists stratified by age, region, and by exposure to perinatal ART. Primary outcome was change in viral load between baseline and 4 years. Analysis was by intention to treat, which we defined as all patients that started treatment. This study is registered with ISRCTN, number ISRCTN73318385. Findings Between Sept 25, 2002, and Sept 7, 2005, 266 children (median age 6.5 years; IQR 2.8-12.9) were randomly assigned treatment regimens: 66 to receive protease inhibitor and switch to second-line at 1000 copies per mL (PI-low), 65 protease inhibitor and switch at 30,000 copies per mL (PI-higher), 68 NNRTI and switch at 1000 copies per mL (NNRTI-low), and 67 NNRTI and switch at 30,000 copies per mL (NNRTI-higher). Median follow-up was 5.0 years (IQR 4.2-6.0) and 188 (71%) children were on first-line ART at trial end. At 4 years, mean reductions in viral load were -3.16 log(10) copies per mL for protease inhibitors versus -3.31 log(10) copies per mL for NNRTIs (difference -0.15 log(10) copies per mL, 95% CI -0.41 to 0.11; p=0.26), and -3.26 log(10) copies per mL for switching at the low versus -3.20 log(10) copies per mL for switching at the higher threshold (difference 0.06 log(10) copies per mL, 95% CI -0.20 to 0.32; p=0.56). Protease inhibitor resistance was uncommon and there was no increase in NRTI resistance in the PI-higher compared with the PI-low group. NNRTI resistance was selected early, and about 10% more children accumulated NRTI mutations in the NNRTI-higher than the NNRTI-low group. Nine children had new CDC stage-C events and 60 had grade 3/4 adverse events; both were balanced across randomised groups. Interpretation Good long-term outcomes were achieved with all treatments strategies. Delayed switching of protease-inhibitor-based ART might be reasonable where future drug options are limited, because the risk of selecting for NRTI and protease-inhibitor resistance is low. Funding Paediatric European Network for Treatment of AIDS (PENTA) and Pediatric AIDS Clinical Trials Group (PACTG/IMPAACT).
Published: 2011
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12. Population analysis of the pregnancy-related modifications in lopinavir pharmacokinetics and their possible consequences for dose adjustment

Author: Jean-Marc Tréluyer, Stéphanie Chhun, Gérard Pons, Elie Azria, Marion Bouillon-Pichault, Odile Launay, Emmanuelle Pannier, Anne Krivine, Vincent Jullien, Olivier Taulera, Ghislaine Firtion, Laurent Finkielsztejn, and Alexandra Compagnucci
Subjects: Microbiology (medical), medicine.medical_specialty, Anti-HIV Agents, Metabolic Clearance Rate, Population, Urology, HIV Infections, Pyrimidinones, Pharmacology, Biology, Lopinavir, Plasma, Pharmacokinetics, Pregnancy, medicine, Humans, Tissue Distribution, Pharmacology (medical), Trough Concentration, education, Chromatography, High Pressure Liquid, Volume of distribution, education.field_of_study, medicine.diagnostic_test, Gestational age, medicine.disease, Infectious Diseases, Therapeutic drug monitoring, Female, Monte Carlo Method, medicine.drug
Abstract: Objectives To investigate the possible necessity of an increase in lopinavir dose during pregnancy in order to achieve the concentrations previously defined as predictive of virological efficacy. Patients and methods Lopinavir pharmacokinetics were investigated by a population approach performed on 145 HIV-infected women, including 74 pregnant women. The final model was used to determine the probability of achievement of the target trough concentrations by Monte Carlo simulations. Results The typical population estimates (inter-individual variability %) of apparent clearance (CL/F) and volume of distribution were 4.38 L/h (24%) and 58.4 L (59%), respectively. Pregnancy associated with a gestational age >15 weeks and delivery were found to increase lopinavir CL/F by 39% and 58%, respectively. With the standard 400 mg twice-a-day regimen, the probability of reaching the 1 mg/L target trough concentration for protease inhibitor (PI)-naive patients was 99% and 96% for non-pregnant and pregnant women, respectively. An important decrease in the probability of achieving the 5.7 mg/L target trough concentration for salvage therapy was observed for non-pregnant women (55%), this decrease being even greater for pregnant women (21%). Raising the lopinavir dose to 600 mg twice daily increased these probabilities to 87% and 53% for non-pregnant and pregnant women, respectively. Conclusions Modification of the lopinavir dose is unlikely to be required for PI-naive pregnant women; however, in pregnant women who have previously received a PI, therapeutic drug monitoring and/or empirical increasing of the dose should be considered.
Published: 2009

13. Pregnancy outcomes in women with HIV type-1 receiving a lopinavir/ritonavir-containing regimen

Author: Jean Patrick Le Meaux, Dominique Cabrol, Olivier Taulera, Thomas Schmitz, Odile Launay, Constance Moutafoff, Emmanuelle Pannier, Anne Krivine, Alexandra Compagnucci, Vassilis Tsatsaris, Ghislaine Firtion, Laurent Finkielsztejn, and Elie Azria
Subjects: Adult, medicine.medical_specialty, Lopinavir/ritonavir, HIV Infections, Pyrimidinones, Lopinavir, Cohort Studies, Obstetric Labor, Premature, Acquired immunodeficiency syndrome (AIDS), Pregnancy, Internal medicine, medicine, Humans, Pharmacology (medical), Pregnancy Complications, Infectious, Sida, Adverse effect, Pharmacology, Ritonavir, biology, business.industry, Pregnancy Outcome, HIV Protease Inhibitors, medicine.disease, biology.organism_classification, Regimen, Infectious Diseases, Immunology, HIV-1, Drug Therapy, Combination, Female, France, business, medicine.drug
Abstract: Background The pregnancy-related adverse effects of antiretroviral therapy (ART) have yielded discordant results, which could be explained in part by the heterogeneity of ART protocols. The objective of our study was to explore whether lopinavir/ritonavir (LPV/r) exposure during pregnancy is associated with adverse outcomes. Methods Data on 100 consecutive HIV type-1 (HIV-1)-infected women receiving LPV/r during pregnancy and who delivered after 15 weeks gestational age (GA) between January 2003 and June 2007 in a single centre were analysed. For each HIV-1-infected woman, two uninfected women matched by age, parity and geographical origin were selected among patients delivering during the same period. Preterm delivery (PTD), vasculoplacental complications, gestational glucose intolerance and post-partum complication rates were compared between cases and controls. Factors associated with PTD and post-partum complications were assessed in HIV-1-infected women by a logistic regression model. Results Rates of vasculoplacental complication and gestational glucose intolerance were not higher among HIV-1-infected women than in controls. PTD was higher in HIV-1-infected women (21%) than in controls (10%; PConclusions In this population of HIV-1-infected pregnant women receiving LPV/r, the risk of PTD was higher than in HIV-1-uninfected controls. As PTD risk was not associated with early exposure to LPV/r, these data support current guidelines to initiate ART earlier in pregnancy.
Published: 2008

14. Early antiretroviral therapy in children perinatally infected with HIV: a unique opportunity to implement immunotherapeutic approaches to prolong viral remission

Author: Carlo Giaquinto, Britta Wahren, Paolo Palma, Jintanat Ananworanich, Nigel Klein, Deenan Pillay, Caroline Foster, María Ángeles Muñoz-Fernández, Stefania Bernardi, Anita De Rossi, William Borkowsky, Eleni Nastouli, Alexandra Compagnucci, Savita Pahwa, Pablo Rojo, Paola Zangari, Paolo Rossi, Katherine Luzuriaga, Vincent Calvez, and DM Gibb
Subjects: Viral rebound, medicine.medical_specialty, Adolescent, Population, Human immunodeficiency virus (HIV), Placebo-controlled study, HIV Infections, medicine.disease_cause, Immune system, Early Medical Intervention, Medicine, Humans, education, Intensive care medicine, Child, Settore MED/38 - Pediatria Generale e Specialistica, education.field_of_study, business.industry, Transmission (medicine), Incidence (epidemiology), Infant, Newborn, Infant, Viral Vaccines, Antiretroviral therapy, Infectious Disease Transmission, Vertical, Infectious Diseases, Anti-Retroviral Agents, Child, Preschool, Immunology, Immunotherapy, business
Abstract: Summary From the use of antiretroviral therapy to prevent mother-to-child transmission to the possibility of HIV cure hinted at by the Mississippi baby experience, paediatric HIV infection has been pivotal to our understanding of HIV pathogenesis and management. Daily medication and indefinite antiretroviral therapy is recommended for children infected with HIV. Maintenance of life-long adherence is difficult and the incidence of triple-class virological failure after initiation of antiretroviral therapy increases with time. This challenge shows the urgent need to define novel strategies to provide long-term viral suppression that will allow safe interruption of antiretroviral therapy without viral rebound and any associated complications. HIV-infected babies treated within a few days of birth have a unique combination of a very small pool of integrated viruses, a very high proportion of relatively HIV resistant naive T cells, and an unparalleled capacity to regenerate an immune repertoire. These features make this group the optimum model population to investigate the potential efficacy of immune-based therapies. If successful, these investigations could change the way we manage HIV infection.
Published: 2014

15. Highly active antiretroviral therapy started in infants under 3 months of age

Author: M Debre, Carlo Giaquinto, Diana M. Gibb, Marie-Laure Chaix, Albert Faye, Aboulker Jp, Lynda Harper, Alexandra Compagnucci, Yacine Saidi, AS Walker, A Babiker, and JH Darbyshire
Subjects: Male, medicine.medical_specialty, Immunology, HIV Infections, Drug resistance, Antiretroviral Therapy, Highly Active, Internal medicine, Drug Resistance, Viral, Humans, Immunology and Allergy, Medicine, Prospective Studies, Adverse effect, Prospective cohort study, Didanosine, Nelfinavir, business.industry, Stavudine, Infant, Newborn, Infant, Viral Load, CD4 Lymphocyte Count, Surgery, Treatment Outcome, Infectious Diseases, Tolerability, HIV-1, RNA, Viral, Female, business, Viral load, Follow-Up Studies, medicine.drug
Abstract: OBJECTIVE: To assess the feasibility and impact of highly active antiretroviral therapy (HAART) started in vertically HIV-1-infected infants less than 3 months of age. DESIGN: A multicentre, phase I/II, non-randomized, open-label study (PENTA 7). METHODS: Adverse events, plasma HIV-1 RNA, CD4 cell counts, CD4 cell percentage (CD4%) and clinical progression were recorded at baseline and prospectively to 72 weeks in order to assess the toxicity, tolerability and efficacy of a combination of stavudine, didanosine and nelfinavir. Selection of genotypic resistance was also investigated. RESULTS: Twenty infants, of whom only three had Centers for Disease Control and Prevention stage B, initiated HAART at median age 2.5 months (range, 0.9-4.7) with median HIV-1 RNA concentration 5.5 log10 copies/ml (range, 3.2-6.8) and CD4% 33% (range, 11-66). Median follow-up was 96 weeks (range, 60-144). At week 72, 11 infants were still taking the original treatment. Few adverse events were reported related to treatment, all minor and causing treatment interruption in only three infants. No AIDS-defining events occurred; one child died of non-HIV-related causes (prematurity). All but two had CD4% > 25% at 72 weeks; however, 14 infants had virological failure and six acquired resistance mutations. CONCLUSIONS: Early treatment with stavudine, didanosine and nelfinavir was well tolerated and associated with good clinical and immunological outcomes at week 72. However, a high rate of virological failure with emergence of genotypic resistance is of great concern. More palatable drug combinations for infants and closer drug monitoring are required.
Published: 2004

16. Dénutrition et infections bronchopulmonaires

Author: Emmanuelle Bady, Alexandra Compagnucci, Laurence Marsal, and Jean-Pierre Laaban
Subjects: Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract: Resume La denutrition accroit le risque d'infections bronchopulmonaires par des mecanismes multiples faisant intervenir une alteration des defenses immunitaires, en particulier de l'immunite a mediation cellulaire, et des mecanismes non immunitaires, notamment une augmentation de l'adherence bacterienne. L'existence d'une denutrition chez un patient hospitalise est un facteur de risque de survenue d'une pneumopathie nosocomiale, en particulier dans les services de chirurgie et de geriatrie. Chez les enfants vivant dans des pays en voie de developpement, la denutrition augmente la morbidite et la mortalite des infections respiratoires. Les relations entre denutrition et infections respiratoires ont ete tres peu etudiees chez les insuffisants respiratoires chroniques.
Published: 1994

17. A randomized controlled trial of genotypic HIV drug resistance testing in HIV-1-infected children: the PERA (PENTA 8) trial

Author: Hannah, Green, Diana M, Gibb, Alexandra, Compagnucci, Vania, Giacomet, Anita, de Rossi, Lynda, Harper, Yacine, Saïdi, Guido, Castelli-Gattinara, Deenan, Pillay, Abdel G, Babiker, Jean-Pierre, Aboulker, Hermione, Lyall, Lee T, Bacheler, A Sarah, Walker, Marianne, Debré, Raffaella, Rosso, David M, Burger, Marinella, Della Negra, David T, Dunn, and Carlo, Giaquinto
Subjects: Male, Adolescent, Infant, HIV Infections, Europe, Treatment Outcome, Anti-Retroviral Agents, Species Specificity, Child, Preschool, Drug Resistance, Viral, HIV-1, Humans, Female, Child, Brazil
Abstract: To evaluate the longer-term utility of genotypic resistance testing in HIV-1-infected children with virological failure.Children aged 3 months-18 years switching antiretroviral therapy (ART) with HIV-1 RNA2,000 copies/ml were randomized between genotypic testing (Virtual Phenotype) and no testing at baseline and subsequent virological failures. Children were followed to at least 96 weeks.One hundred and seventy eligible children, from 24 clinical centres in six countries, were randomized to resistance testing (n = 87) or no testing (n = 83) between June 2000-July 2003. At baseline, mean HIV-1 RNA and CD4+ T-cell percentage were 4.7 log10 copies/ml and 20%, respectively. Children had taken ART for a mean of 5 years; 24% had received all three classes, 53% nucleoside reverse transcriptase inhibitors (NRTIs)+protease inhibitors (PIs), 9% NRTIs+non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 14% NRTIs only. There was no difference between the arms in the drug classes or the individual PIs/NNRTIs prescribed. However, 49% in the resistance test arm (RT) versus 19% in the no-test arm (NT) continued at least one NRTI from their failing regimen; 56% versus 19% were prescribed didanosine+stavudine as their NRTI backbone. Adjusting for baseline HIV-1 RNA, mean reductions in HIV-1 RNA at 48 weeks were 1.51 log10 copies/ml in the RT arm and 1.23 in the NT arm (P = 0.3); the difference between the arms was smaller at week 96 (RT: 1.50, NT: 1.47; P = 0.9).In this first paediatric trial of resistance testing, we observed a substantial difference in NRTI-prescribing behaviour across arms. However statistically significant evidence of a long-term virological or immunological benefit was not observed. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN14367816.
Published: 2007

18. Bayesian parameter estimates of nelfinavir and its active metabolite, hydroxy-tert-butylamide, in infants perinatally infected with human immunodeficiency virus type 1

Author: Salomé Payen, Françoise Bressolle, Albert Faye, Diana Gibbs, Carlo Giaquinto, Evelyne Jacqz-Aigrain, Roberto Gomeni, and Alexandra Compagnucci
Subjects: Aging, Spectrometry, Mass, Electrospray Ionization, Metabolite, Population, HIV Infections, Pharmacology, Models, Biological, chemistry.chemical_compound, Elimination rate constant, Pharmacokinetics, medicine, Humans, Pharmacology (medical), Drug Interactions, education, Active metabolite, Chromatography, High Pressure Liquid, education.field_of_study, Nelfinavir, biology, Body Weight, Infant, Newborn, Infant, Bayes Theorem, HIV Protease Inhibitors, Didanosine, Stavudine, Infectious Diseases, chemistry, Enzyme inhibitor, Immunology, biology.protein, HIV-1, Reverse Transcriptase Inhibitors, medicine.drug, Nelfinavir mesylate, Half-Life
Abstract: The objective of the present study was to develop a population pharmacokinetic model for nelfinavir mesylate (NFV) and nelfinavir hydroxy-tert-butylamide (M8), the most abundant metabolite of NFV, in infants vertically infected with human immunodeficiency virus type 1 and participating in the Paediatric European Network for Treatment of AIDS 7 study. Plasma NFV concentrations were determined during repeated NFV administrations (two to three times a day). Eighteen infants younger that age 2 years participated in this study. The doses administered ranged from 71 to 203 mg/kg of body weight/day. Pharmacokinetic parameter estimates were obtained by a compartmental approach by using a kinetic model to simultaneously fit NFV and M8 (active metabolite) concentrations. M8 was shown to be formation rate limited and was characterized by first-order rate constants of formation and elimination. Body weight was found to be a more appropriate predictor than age of the changes in (i) the rate of metabolism, (ii) the elimination rate constant of NFV, and (iii) NFV clearance. Population parameters were computed to account for the relationship between the rate of metabolism and body weight. The estimated NFV and M8 elimination half-lives were 4.3 and 2.04 h, respectively. The estimated NFV clearance was 2.13 liters/h/kg. The M8 concentration-to-NFV concentration ratio was 0.64 ± 0.44. In conclusion, the population pharmacokinetic model describing the dispositions of NFV and M8 should facilitate the design of future studies to elucidate the relative contributions of the parent compound and M8 to the pharmacological and toxic effects of NFV therapy.
Published: 2005

19. Persistence of multidrug-resistant HIV-1 without antiretroviral treatment 2 years after sexual transmission

Author: Christine Katlama, Vincent Calvez, Anne-Geneviève Marcelin, Laurence Morand-Joubert, Constance Delaugerre, Pierre-Marie Girard, Odile Picard, Anne Krivine, Alexandra Compagnucci, Marie-Laure Chaix, and Véronique Schneider
Subjects: Adult, Male, Sexual transmission, Genotype, Population, HIV Infections, Viral quasispecies, Fatal Outcome, Drug Resistance, Multiple, Viral, HIV Protease, Disease Transmission, Infectious, Humans, Pharmacology (medical), Seroconversion, education, Pharmacology, education.field_of_study, biology, Homosexuality, Middle Aged, biology.organism_classification, Virology, Genes, pol, HIV Reverse Transcriptase, Infectious Diseases, Anti-Retroviral Agents, Lentivirus, Immunology, DNA, Viral, Mutation, HIV-1, Leukocytes, Mononuclear, Viral disease, Viral load, Sequence Alignment, HIV drug resistance, Follow-Up Studies
Abstract: Objectives To understand the virological mechanisms of 2-year persistence of multidrug-resistant virus without selective antiretroviral pressure in HIV-1-infected patients. Patients and Methods Two patients were contaminated recently by their HIV-1-infected partners, who had received, before the transmission, all available antiretroviral drugs and who exhibited a severe therapeutic failure. The resistance mutations analysis was performed by clonal sequencing of 1.2 kb of pol gene in plasma of index and sources patients. Sequencing of HIV-1 DNA was performed in PBMCs of index patients. Results Genotypic testing performed in index patients at time of seroconversion showed resistance mutations to three classes of drugs. All mutations were linked on the same viral genome and all quasispecies carried all mutations. No wild-type virus was detected. The same results were found in source patients and showed that all mutations were transmitted. In the index patients, all mutations persisted over 2 years without antiretroviral treatment. Moreover, the resistance mutations were all archived in the cellular reservoir. Viral load and CD4 count of index patients remained unchanged during 2 years of follow-up. Discussion Only multidrug-resistant viruses were detected in the source patients and could be transmitted in index patients. In the latter, an expansion of predominant multidrug-resistant quasispecies and the ‘archival’ of all mutations were observed. These results explain the persistence of mutations and suggest that it is highly difficult to return to a wild-type viral population, sensitive to an antiretroviral treatment. The treatment of index patients is limited and the major risk is the transmission of these multidrug-resistant viruses. This work was presented in part in the XII International HIV Drug Resistance Workshop, Los Cabos, Mexico, June 2003; and in the 2nd IAS Conference on HIV Pathogenesis & Treatment, Paris, France, July 2003.
Published: 2004

20. O222 Treatment interruption in children with chronic HIV-infection: the results of the paediatric European network for treatment of AIDS (PENTA) 11 trial

Author: F Monpoux, C Taylor, S Kanjavanit, Carlo Giaquinto, Nicole Ngo-Giang-Huong, Hannah Green, Uwe Wintergerst, Lynne M. Mofenson, Marc Lallemant, David Nadal, Alexandra Compagnucci, Yacine Saidi, Magdalena Marczyńska, Mig Tomé, Hermione Lyall, Diana M. Gibb, and J Moye
Subjects: Pediatrics, medicine.medical_specialty, business.industry, Public health, Public Health, Environmental and Occupational Health, Human immunodeficiency virus (HIV), medicine.disease, medicine.disease_cause, Infectious Diseases, Acquired immunodeficiency syndrome (AIDS), Treatment interruption, Immunology, medicine, Presentation (obstetrics), business
Abstract: ss Open Acce Oral presentation O222 Treatment interruption in children with chronic HIV-infection: the results of the paediatric European network for treatment of AIDS (PENTA) 11 trial DM Gibb*1, A Compagnucci2, H Green3, M Lallemant4, Y Saidi2, N NgoGiang-Huong4, C Taylor3, L Mofenson5, F Monpoux6, MIG Tome7, M Marczynska8, D Nadal9, U Wintergerst10, S Kanjavanit11, H Lyall12, C Giaquinto13 and J Moye4
Published: 2008

21. Evolution of antiretroviral phenotypic and genotypic drug resistance in antiretroviral-naive HIV-1-infected children treated with abacavir/lamivudine, zidovudine/lamivudine or abacavir/zidovudine, with or without nelfinavir (the PENTA 5 trial)

Author: Clive Loveday, Deenan Pillay, Mounir Ait-Khaled, David Dunn, Abdel Babiker, Anita De Rossi, María Ángeles Muñoz-Fernández, A. Sarah Walker, Alexandra Compagnucci, Steve Kaye, and Diana M. Gibb
Subjects: Genotype, Anti-HIV Agents, Drug resistance, Biology, Zidovudine, HIV-1 REVERSE-TRANSCRIPTASE, Acquired immunodeficiency syndrome (AIDS), Abacavir, immune system diseases, Drug Resistance, Viral, medicine, Humans, Pharmacology (medical), Protease inhibitor (pharmacology), Child, Pharmacology, Acquired Immunodeficiency Syndrome, Nelfinavir, Abacavir/Lamivudine/Zidovudine, Lamivudine, virus diseases, medicine.disease, Virology, Dideoxynucleosides, VIROLOGICAL RESPONSE, COMBINATION THERAPY, Phenotype, Infectious Diseases, Immunology, HIV-1, RNA, Viral, HIV-1 REVERSE-TRANSCRIPTASE, COMBINATION THERAPY, VIROLOGICAL RESPONSE, Drug Therapy, Combination, medicine.drug
Abstract: Purpose and methodsTo describe the evolution of resistance to zidovudine (ZDV), lamivudine (3TC), abacavir (ABC) and nelfinavir (NFV), 113 previously untreated children in the PENTA 5 trial had resistance assayed at baseline, rebound and/or 24, 48, 72 weeks (VIRCO: phenotyping and genotyping with ‘Virtual Phenotype’ interpretation).ResultsAt baseline, few reverse transcriptase mutations and no primary protease inhibitor mutations were observed. Time to detectable HIV-1 RNA with reduced phenotypic susceptibility to any drug was shortest in the ZDV+3TC arm (overall logrank P=0.02). Through a median follow-up of 55 weeks, at their last assessment 11 (28%), 16 (40%) and 13 (32%) children with detectable HIV-1 RNA and a resistance test available had mutations conferring resistance to none, one, or two or more trial drugs, respectively, according to the virtual phenotype. Reduced phenotypic susceptibility to ABC only occurred in the 3TC+ABC arm and required K65R and/or L74V in addition to M184V. NFV-resistant virus was selected slowly through D30N or L90M pathways, and selection of ZDV-resistant virus was rare.ConclusionsSelection of 3TC-resistant virus was most frequent, followed by NFV and/or ABC; selection of ZDV-resistant virus was rare. Importantly, although in vitro, ABC selects for M184V as the first mutation, ABC did not select for M184V when combined with ZDV without 3TC. The most sustained HIV-1 RNA response was in the 3TC+ABC arm, but mutations conferring reduced susceptibility to 3TC and/or ABC evolved more frequently if virological failure occurred with 3TC+ABC than with ZDV+ABC.

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21 results on '"Alexandra Compagnucci"'

2. ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing

3. Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents and young adults (BREATHER): Extended follow-up results of a randomised, open-label, non-inferiority trial.

4. Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children

5. Once-daily dolutegravir-based antiretroviral therapy in infants and children living with HIV from age 4 weeks: results from the below 14 kg cohort in the randomised ODYSSEY trial

6. Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

7. ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing

8. Long-term clinical, virological and immunological outcomes following planned treatment interruption in HIV-infected children

9. The EPIICAL project: an emerging global collaboration to investigate immunotherapeutic strategies in HIV-infected children

10. Hepatic, Renal, Hematologic, and Inflammatory Markers in HIV-Infected Children on Long-term Suppressive Antiretroviral Therapy

11. First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, randomised phase 2/3 trial

12. Population analysis of the pregnancy-related modifications in lopinavir pharmacokinetics and their possible consequences for dose adjustment

13. Pregnancy outcomes in women with HIV type-1 receiving a lopinavir/ritonavir-containing regimen

14. Early antiretroviral therapy in children perinatally infected with HIV: a unique opportunity to implement immunotherapeutic approaches to prolong viral remission

15. Highly active antiretroviral therapy started in infants under 3 months of age

16. Dénutrition et infections bronchopulmonaires

17. A randomized controlled trial of genotypic HIV drug resistance testing in HIV-1-infected children: the PERA (PENTA 8) trial

18. Bayesian parameter estimates of nelfinavir and its active metabolite, hydroxy-tert-butylamide, in infants perinatally infected with human immunodeficiency virus type 1

19. Persistence of multidrug-resistant HIV-1 without antiretroviral treatment 2 years after sexual transmission

20. O222 Treatment interruption in children with chronic HIV-infection: the results of the paediatric European network for treatment of AIDS (PENTA) 11 trial

21. Evolution of antiretroviral phenotypic and genotypic drug resistance in antiretroviral-naive HIV-1-infected children treated with abacavir/lamivudine, zidovudine/lamivudine or abacavir/zidovudine, with or without nelfinavir (the PENTA 5 trial)

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21 results on '"Alexandra Compagnucci"'

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