Population Pharmacokinetics of Dolutegravir in African Children: Results From the CHAPAS-4 Trial

Hylke Waalewijn; Roeland E Wasmann; Alasdair Bamford; Diana M Gibb; Helen M McIlleron; Angela Colbers; David M Burger; Paolo Denti; CHAPAS-4 trial team

doi:10.1093/jpids/piae076

Population Pharmacokinetics of Dolutegravir in African Children: Results From the CHAPAS-4 Trial

J Pediatric Infect Dis Soc. 2024 Sep 26;13(9):496-500. doi: 10.1093/jpids/piae076.

Authors

Collaborators

CHAPAS-4 trial team:
Di Gibb, Sarah Walker, Anna Turkova, Clare Shakeshaft, Moira Spyer, Margaret Thomason, Anna Griffiths, Lara Monkiewicz, Sue Massingham, Alex Szubert, Alasdair Bamford, Katja Doerholt, Amanda Bigault, Nimisha Dudakia, Annabelle South, Nadine Van Looy, Carly Au, Hannah Sweeney, Cissy M Kityo, Victor Musiime, Eva Natukunda, Esether Nambi, Diana Rutebarika Antonia, Rashida Nazzinda, Imelda Namyalo, Joan Nangiya, Lilian Nabeeta, Aidah Nakalyango, Lilian Kobusingye, Caroline Otike, Winnie Namala, Phionah Ampaire, Ayesiga Edgar, Claire Nasaazi, Milly Ndigendawani, Paul Ociti, Priscilla Kyobutungi, Ritah Mbabazi, Phyllis Mwesigwa Rubondo, Juliet Ankunda, Mariam Naabalamba, Mary Nannungi, Alex Musiime, Faith Mbasani, Babu Enoch Louis, Josephine Namusanje, Denis Odoch, Edward Bagirigomwa, Eddie Rubanga, Disan Mulima, Paul Oronon, Eram David Williams, David Baliruno, Josephine Kobusingye, Agnes Uyungrwoth, Barbara Mukanza, Jimmy Okello, Emily Ninsiima, Lutaro Ezra, Christine Nambi, Nansaigi Mangadalen, Musumba Sharif, Nobert B Serunjogi, Otim Thomas, Abbas Lugemwa, Shafic Makumbi, Sharif Musumba, Edward Mawejje, Ibrahim Yawe, Linda Jovia Kyomuhendo, Mariam Kasozi, Rogers Ankunda, Samson Kariisa, Christine Inyakuwa, Emily Ninsiima, Lorna Atwine, Beatrice Tumusiime, John Ahuura, Deogracious Tukwasibwe, Violet Nagasha, Judith Kukundakwe, Mariam Zahara Nakisekka, Ritah Winnie Nambejja, Mercy Tukamushaba, Rubinga Baker, Edridah Keminyeto, Barbara Ainebyoona, Sula Myalo, Juliet Acen, Nicholas Jinta Wangwe, Ian Natuhurira, Gershom Kananura Natukunatsa, Veronica Mulenga, Chishala Chabala, Joyce Chipili Lungu, Monica Kapasa, Khonzya Zyambo, Kevin Zimba, Dorothy Zangata, Ellen Shingalili, Naomi Mumba, Nayunda Kaonga, Mukumbi Kabesha, Oliver Mwenechanya, Terrence Chipoya, Friday Manakalanga, Stephen Malama, Daniel Chola, Bwendo Nduna, Mwate Mwamabazi, Kabwe Banda, Beatrice Kabamba, Muleya Inambao, Pauline Mahy Mukandila, Mwizukanji Nachamba, Stella Himabala, Shadrick Ngosa, Davies Sondashi, Collins Banda, Mark Munyangabe, Grace Mbewe Ngoma, Sarah Chimfwembe, Mercy Lukonde Malasha, Mumba Kajimalwendo, Henry Musukwa, Shadrick Mumba, James Hakim, Mutsa Bwakura-Dangarembizi, Kusum Nathoo, Taneal Kamuzungu, Ennie Chidziva, Joyline Bhiri, Joshua Choga, Hilda Angela Mujuru, Godfrey Musoro, Vivian Mumbiro, Moses Chitsamatanga, Constantine Mutata, Rudo Zimunhu, Shepherd Mudzingwa, Secrecy Gondo, Columbus Moyo, Ruth Nhema, Kathryn Boyd, Farai Matimba, Vinie Kouamou, Richard Matarise, Zorodzai Tangwena, Taona Mudzviti, Allen Matubu, Alfred Kateta, Victor Chinembiri, Dorinda Mukura, Joy Chimanzi, Dorothy Murungu, Wendy Mapfumo, Pia Ngwaru, Lynette Chivere, Prosper Dube, Trust Mukanganiki, Sibusisiwe Weza, Tsitsi Gwenzi, Shirley Mutsai, Misheck Phiri, Makhosonke Ndlovu, Tapiwa Gwaze, Stuart Chitongo, Winisayi Njaravani, Sandra Musarurwa, Cleopatra Langa, Sue Tafeni, Wilbert Ishemunyoro, Nathalie Mudzimirema, Wedu Ndebele, Mary Nyathi, Grace Siziba, Getrude Tawodzera, Tracey Makuchete, Takudzwa Chidarura, Shingaidzo Murangandi, Lawrence Mafaro, Owen Chivima, Sifiso Dumani, Beaullar Mampondo, Constance Maphosa, Debra Mwale, Rangarirai Dhlamini, Thabani Sibanda, Nobukhosi Madubeko, Silibaziso Nyathi, Zibusiso Matiwaza, Sylvia Nabukenya, Harriet Tibakabikoba, Sarah Nakalanzi, Cynthia Williams, Precious Chandiwana, Winnie Gozhora, Benedictor Dube, Sylvia Mulambo, Hope Mwanyungwi, David Burger, Angela Colbers, Hylke Waalewijn, Lisanne Bevers, Shaghayegh Mohsenian-Naghani, Helen McIlleron, Jennifer Norman, Lubbe Wiesner, Roeland Wasmann, Paolo Denti, Lufina Tsirizani Galileya, Eva Natukunda, Victor Musiime, Phillipa Musoke, Paul Revill, Simon Walker, Adeodata Kekitiinwa, Angela Mushavi, Febby Banda Kawamya, Denis Tindyebwa, Hermione Lyall, Ian Weller, Tim Peto, Philippa Musoke, Margaret Siwale, Rose Kambarami, Johanna Roth, Pauline Beattie

Affiliations

¹ Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
² Department of Pharmacy, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, The Netherlands.
³ Medical Research Council Clinical Trials Unit, University College London, London, UK.
⁴ Infection, Immunity & Inflammation Department, UCL Great Ormond Street Hospital Institute of Child Health, London, UK.
⁵ Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.

Abstract

We characterized population pharmacokinetics in 42 African children receiving once-daily 25 mg (14 to <20 kg) or 50 mg (>20 kg) dolutegravir. Coadministration with emtricitabine and tenofovir alafenamide reduced dolutegravir bioavailability by 19.6% (95% confidence interval: 8.13%-30.8%) compared with zidovudine or abacavir with lamivudine. Nevertheless, concentrations remained above efficacy targets, confirming current dosing recommendations.

Keywords: HIV; children; dolutegravir; pharmacokinetic; population pharmacokinetics.

Publication types

Randomized Controlled Trial

MeSH terms

Adenine / analogs & derivatives
Adenine / pharmacokinetics
Adenine / therapeutic use
Adolescent
Alanine / analogs & derivatives
Alanine / pharmacokinetics
Alanine / therapeutic use
Anti-HIV Agents* / administration & dosage
Anti-HIV Agents* / blood
Anti-HIV Agents* / pharmacokinetics
Anti-HIV Agents* / therapeutic use
Biological Availability
Child
Child, Preschool
Dideoxynucleosides / administration & dosage
Dideoxynucleosides / pharmacokinetics
Dideoxynucleosides / therapeutic use
Drug Interactions
Drug Therapy, Combination
Emtricitabine / administration & dosage
Emtricitabine / pharmacokinetics
Emtricitabine / therapeutic use
Female
HIV Infections* / drug therapy
HIV Integrase Inhibitors / administration & dosage
HIV Integrase Inhibitors / pharmacokinetics
HIV Integrase Inhibitors / therapeutic use
Heterocyclic Compounds, 3-Ring* / administration & dosage
Heterocyclic Compounds, 3-Ring* / blood
Heterocyclic Compounds, 3-Ring* / pharmacokinetics
Heterocyclic Compounds, 3-Ring* / therapeutic use
Humans
Lamivudine / administration & dosage
Lamivudine / pharmacokinetics
Lamivudine / therapeutic use
Male
Oxazines* / pharmacokinetics
Piperazines* / pharmacokinetics
Pyridones* / pharmacokinetics
Tenofovir / pharmacokinetics
Tenofovir / therapeutic use
Zidovudine / administration & dosage
Zidovudine / pharmacokinetics
Zidovudine / therapeutic use

Substances

Pyridones
Heterocyclic Compounds, 3-Ring
Oxazines
Piperazines
dolutegravir
Anti-HIV Agents
Tenofovir
Emtricitabine
Dideoxynucleosides
Lamivudine
HIV Integrase Inhibitors
Alanine
Zidovudine
Adenine

Abstract

Publication types

MeSH terms

Substances

Grants and funding