The toolkit for research and development of paediatric antiretroviral drugs and formulations was developed under the leadership of the Treatment and care team in the HIV Department, WHO, and  supported by the WHO Paediatric Antiretroviral Working Group. The project was led by Martina Penazzato (WHO Paediatric HIV Lead, Geneva, Switzerland) and coordinated by Claire Townsend (WHO consultant, Geneva, Switzerland). Each module was drafted by one or more co-authors (listed in each module), with input from other collaborators and the project team. Designated reviewers reviewed the modules, including at least one member of the Paediatric Antiretroviral Working Group and one external reviewer. Input from representatives of drug manufacturers and regulatory authorities was sought at key stages.

WHO and Unitaid thank everyone who contributed to developing this toolkit, including individuals from the Clinton Health Access Initiative, Drugs for Neglected Diseases initiative, Medicines Patent Pool, ICAP at Columbia University, the European Paediatric Formulation Initiative and the IQ Consortium Drug Product Working Group.

Specifically, we thank the following individuals for their input: Elaine Abrams (ICAP at Columbia University, New York, NY, USA), Sharon Nachman (State University of New York at Stony Brook, USA), Polly Clayden (HIV i-base, London, United Kingdom), Carlo Giaquinto (University of Padua, Italy), Marissa Vicari (International AIDS Society, Geneva, Switzerland) and Diana Gibb (University College London, United Kingdom).

Comments were also provided by the Division of Antiviral Products of the United States Food and Drug Administration and by representatives of the European Medicines Agency and members of the European Medicines Agency Paediatric Committee. Any views expressed in this publication by employees of the United States Food and Drug Administration or the European Medicines Agency, or members of the European Medicines Agency Paediatric Committee, are their own and may not be understood or quoted as being made on behalf of or reflecting the position of the United States Food and Drug Administration or of the European Medicines Agency or any of its committees or working parties.

The contents of this document do not necessarily reflect the official views of the United States Department of State.

The toolkit was developed with the financial support of Unitaid, the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network and the PENTA Foundation. The work of the Clinton Health Access Initiative on optimal antiretroviral drugs for children is made possible through the generous support of Unitaid.

List of partner organizations

Acknowledgements: by module:

  1. Trial design
  2. Pharmacokinetic modelling
  3. Pregnant and breastfeeding women
  4. Coinfections
  5. Acceptability
  6. Community engagement
  7. Target product profiles
  8. Product commercialization
  9. Regulatory filing
  10. Pharmacovigilance

Trial design

Authors: Anna Turkova1 and Theodore Ruel2

Reviewers: Deborah Ford1, Ellen Chadwick3, Diana Gibb1 and Elaine Abrams4

1University College London, United Kingdom; 2University of California, San Francisco, USA; 3Northwestern University, Chicago, IL, USA; 4ICAP at Columbia University, New York, NY, USA

Comments were also provided by the Division of Antiviral Products of the United States Food and Drug Administration and by representatives of the European Medicines Agency and members of the European Medicines Agency Paediatric Committee. Any views expressed in this publication by employees of the United States Food and Drug Administration or the European Medicines Agency, or members of the European Medicines Agency Paediatric Committee, are their own and may not be understood or quoted as being made on behalf of or reflecting the position of the United States Food and Drug Administration or of the European Medicines Agency or any of its committees or working parties.

Pharmacokinetic modelling

Authors: Paolo Denti1, Mark Mirochnick2 and Tim R. Cressey3–5

Reviewers: Helen McIlleron1, Brookie Best6 and Adrie Bekker7

1University of Cape Town, South Africa; 2Boston University School of Medicine, MA, USA; 3Chiang Mai University, Thailand; 4Harvard T.H. Chan School of Public Health, Boston, MA, USA; 5University of Liverpool, United Kingdom; 6University of California, San Diego, USA; 7Stellenbosch University, Cape Town, South Africa

Pregnant and breastfeeding women

Authors: Stein Schalkwijk1, Angela Colbers1 and Mark Mirochnick2

Other contributors: David Burger1

Reviewers: Gerhard Theron3, Alice Stek4, Lynne Mofenson5

1Radboud University Medical Center, Nijmegen, Netherlands; 2Boston University, MA, USA; 3Stellenbosch University, Cape Town, South Africa; 4University of Southern California, Los Angeles, USA; 5Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, USA

Coinfections

Authors:  Anthony J. Garcia-Prats1 and Pablo Rojo2

Other contributors: Giuseppe Indolfi3, Helen McIlleron4 and Helena Rabie1

Reviewers: Mark Cotton1 and Moherndran Archary5

1Stellenbosch University, Cape Town, South Africa; 2Hospital de 12 Octubre, Universidad Complutense, Madrid, Spain; 3Meyer Children’s University Hospital, Florence, Italy; 4University of Cape Town, South Africa; 5University of KwaZulu-Natal, Durban, South Africa

Acceptability

Authors: Marc Lallemant1,2

Contributor: Victor Musiime3,4

Reviewers: Janice Lee5 and Diana F. Clarke6

1Program for HIV Prevention and Treatment, Institut de Recherche pour le Développement, Marseille, France; 2Chiang Mai University, Thailand; 3Makerere University, Kampala, Uganda; 4Joint Clinical Research Centre, Kampala, Uganda; 5Drugs for Neglected Diseases initiative, Geneva, Switzerland; 6Boston Medical Center, MA, USA

The authors are grateful for the input received from the European Paediatric Formulations Initiative and the IQ Consortium Drug Product Pediatric Working Group, especially Catherine Tuleu (University College London, Chair, European Paediatric Formulations Initiative) and David Cheng Thiam Tan (AbbVie, Co-Chair, IQ Consortium) as well as Trupti Dixit (independent), Eleni Dokou (Vertex), Elizabeth Galella (Bristol-Myers Squibb, Co-Chair, IQ Consortium Drug Product Pediatric Working Group), Melissa Keeney (Eli Lilly), John Morris (AbbVie), Yogesh Patil (Amgen), Fabrice Ruiz (Clinsearch), Smita Salunke (University College London), Daniel Schaufelberger (Janssen), Julia Schiele (AbbVie) and Robert L. Ternik (Eli Lilly).

Community engagement

Authors: Djamel Hamadache1 and Polly Clayden2

Other contributors: Dr Sarah Bernays3,4 and Abi Carter5

Reviewers: Marissa Vicari6, Mercy Ngulube5, Gareth Tudor-Williams7 and Janice Lee8

1Independent consultant, London, United Kingdom; 2HIV i-base, London, United Kingdom; 3Sydney Medical School, Australia; 4London School of Hygiene and Tropical Medicine, United Kingdom; 5Children's HIV Association, London, United Kingdom; 6International AIDS Society, Geneva, Switzerland; 7Imperial College London, United Kingdom; 8Drugs for Neglected Diseases initiative, Geneva, Switzerland

Special thanks to Sarah Bernays, Abi Carter and Djamel Hamadache for sharing case studies and young people’s experiences as trial participants.

Target product profiles

Authors: Diana F Clarke1, Fernando Pascual2 and Atieno Ojoo3

Reviewers: Marc Lallemant4,5, Vinod Arora6, Paul La Barre3, Jonathan Howard Brand3 and Nandita Sugandhi7

1Boston Medical Center, MA, USA; 2Medicines Patent Pool, Geneva, Switzerland; 3UNICEF, Copenhagen, Denmark; 4Program for HIV Prevention and Treatment, Institut de Recherche pour le Développement, Marseille, France; 5Chiang Mai University, Thailand; 6Medicines Patent Pool, Gurgaon, Haryana, India; 7Texas A&M Health Science Center, College Station, USA; 8ICAP at Columbia University, New York, NY, USA

Product commercialization

Authors: Nandita Sugandhi1, Fernando Pascual2 and Vineet Prabhu3

Other contributors: Diana F. Clarke4 and Atieno Ojoo5

Reviewers: Carolyn Amole6 and Victor Musiime7,8

1ICAP at Columbia University, New York, NY, USA; 2Medicines Patent Pool, Geneva, Switzerland; 3Clinton Health Access Initiative, Boston, MA, USA; 4Boston Medical Center, MA, USA; 5UNICEF, Copenhagen, Denmark; 6Clinton Health Access Initiative, New York, NY, USA; 7Makerere University, Kampala, Uganda; 8Joint Clinical Research Centre, Kampala, Uganda

Generous support from Unitaid enables the work of the Clinton Health Access Initiative on optimal ARV drugs for children.

Regulatory filing

Authors: Linda Lewis1, Melynda Watkins1 and Francesca Rocchi2,3

Reviewers: Yodit Belew4, Andrea Ecker5 and Victor Musiime6,7

1Clinton Health Access Initiative, Boston, Massachusetts, MA, USA; 2Bambino Gesù Children Hospital, Rome, Italy; 3PENTA Foundation, Padua, Italy; 4United States Food and Drug Administration, Washington, DC, USA; 5European Medicines Agency, London, United Kingdom; 6Makerere University, Kampala, Uganda; 7Joint Clinical Research Centre, Kampala, Uganda

Comments were also provided by the Division of Antiviral Products of the United States Food and Drug Administration and by representatives of the European Medicines Agency and members of the European Medicines Agency Paediatric Committee. Any views expressed in this publication by employees of the United States Food and Drug Administration or the European Medicines Agency, or members of the European Medicines Agency Paediatric Committee, are their own and may not be understood or quoted as being made on behalf of or reflecting the position of the United States Food and Drug Administration or of the European Medicines Agency or any of its committees or working parties.

The work of the Clinton Health Access Initiative on optimal antiretroviral drugs for children is made possible through the generous support of Unitaid.

Pharmacovigilance

Authors: Ali Judd1, Intira Jeannie Collins1, Hiwot Haile-Selassie2, Natella Rakhmanina3 and Miriam Sturkenboom4

Other contributors: Françoise Renaud2

Reviewers: Andy Stergachis5 and Karen Cohen6

1University College London, United Kingdom; 2World Health Organization, Geneva, Switzerland; 3Elizabeth Glaser Paediatric AIDS Foundation, Washington, DC, USA; 4University Medical Center Utrecht, Netherlands; 5University of Washington, Seattle, USA; 6University of Cape Town, South Africa