Elaine J Abrams1, Lynne M Mofenson2, Anton Pozniak3, Shahin Lockman4, Angela Colbers5, Yodit Belew6, Polly Clayden7, Mark Mirochnick8, George K Siberry9, Nathan Ford10, Saye Khoo11, Francoise Renaud10, Marco Vitoria10, Willem Daniel Francois Venter12, Meg Doherty10, Martina Penazzato10. 1. ICAP at Columbia University, Mailman School of Public Health, Columbia University and Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA. 2. Elizabeth Glaser Pediatric AIDS Foundation, Washington DC, USA. 3. Chelsea and Westminster Hospital NHS Foundation Trust and LSHTM London, UK. 4. Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health (both in Boston, MA, USA). 5. Radboud University Medical Center, Nijmegen, and HIV Institute, the Netherlands. 6. United States Food & Drug Administration. 7. HIV i-Base, London, UK. 8. Boston University School of Medicine, Boston, MA. 9. Office of HIV/AIDS, United States Agency for International Development (USAID), Washington, DC, USA. 10. Global HIV, Hepatitis and STIs Programme, World Health Organization, Geneva, Switzerland. 11. Department of Pharmacy, Research Institute, University of Liverpool, UK. 12. Ezintsha, Wits Reproductive Health Sciences, University of Witwatersrand, South Africa.
Abstract
BACKGROUND: Concerns have been voiced that the exclusion of pregnant women from clinical trials results in a lack of safety and pharmacokinetic data for antiretroviral drugs (ARVs) in pregnancy, creating clear risks to pregnant women living with HIV (PWLHIV) and their infants. SETTING: The World Health Organization convened a Paediatric Antiretroviral Drug Optimization (PADO) group meeting, December 10-12, 2018, in Geneva, Switzerland METHODS: : The group, comprised of clinicians, scientists, HIV programme managers, regulators and community representatives, were tasked to: consider how ARVs are studied in PWLHIV; define alternative approaches to studying ARVs in PWLHIV; identify ways to shorten the timeline to determine safe use of new agents during pregnancy; and define strategies to collaborate with regulators and industry to change longstanding practices. RESULTS: Most new ARV's are not studied in pregnant populations until after drug licensure, primarily opportunistically among women who become pregnant while taking the ARV of interest. Acceleration of the timeline will require earlier completion of preclinical studies and a a new paradigm: namely - under certain conditions - allow women who become pregnant while participating in Phase III ARV studies the option of remaining on study and enroll pregnant women into Phase III trials of new agents to obtain preliminary safety and dosing and efficacy data. CONCLUSION: A revision of the current approach to the study of antiretrovirals in pregnant women is urgently needed to improve timely access and safe use of new agents during pregnancy.
BACKGROUND: Concerns have been voiced that the exclusion of pregnant women from clinical trials results in a lack of safety and pharmacokinetic data for antiretroviral drugs (ARVs) in pregnancy, creating clear risks to pregnant women living with HIV (PWLHIV) and their infants. SETTING: The World Health Organization convened a Paediatric Antiretroviral Drug Optimization (PADO) group meeting, December 10-12, 2018, in Geneva, Switzerland METHODS: : The group, comprised of clinicians, scientists, HIV programme managers, regulators and community representatives, were tasked to: consider how ARVs are studied in PWLHIV; define alternative approaches to studying ARVs in PWLHIV; identify ways to shorten the timeline to determine safe use of new agents during pregnancy; and define strategies to collaborate with regulators and industry to change longstanding practices. RESULTS: Most new ARV's are not studied in pregnant populations until after drug licensure, primarily opportunistically among women who become pregnant while taking the ARV of interest. Acceleration of the timeline will require earlier completion of preclinical studies and a a new paradigm: namely - under certain conditions - allow women who become pregnant while participating in Phase III ARV studies the option of remaining on study and enroll pregnant women into Phase III trials of new agents to obtain preliminary safety and dosing and efficacy data. CONCLUSION: A revision of the current approach to the study of antiretrovirals in pregnant women is urgently needed to improve timely access and safe use of new agents during pregnancy.
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