Enhanced and Timely Investigation of ARVs for Use in Pregnant Women

doi:10.1097/QAI.0000000000002597

. 2021 Apr 15;86(5):607-615.

doi: 10.1097/QAI.0000000000002597.

Enhanced and Timely Investigation of ARVs for Use in Pregnant Women

Elaine J Abrams^{1

2}, Lynne M Mofenson³, Anton Pozniak⁴, Shahin Lockman^{5

6

7}, Angela Colbers⁸, Yodit Belew⁹, Polly Clayden¹⁰, Mark Mirochnick¹¹, George K Siberry¹², Nathan Ford¹³, Saye Khoo¹⁴, Francoise Renaud¹³, Marco Vitoria¹³, Willem D F Venter¹⁵, Meg Doherty¹³, Martina Penazzato¹³; PADO and CADO Experts Groups

Affiliations

¹ ICAP at Columbia University, Mailman School of Public Health, Columbia University, New York, NY.
² Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.
³ Research Program, Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC.
⁴ HIV and Sexual Health Clinic, Chelsea and Westminster Hospital NHS Foundation Trust and LSHTM London, London, United Kingdom.
⁵ Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA.
⁶ Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA.
⁷ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
⁸ Radboud University Medical Center, and HIV Institute, Nijmegen, the Netherlands.
⁹ Division of Antiviral Products, US Food and Drug Administration (FDA), Silver Spring, MD.
¹⁰ HIV i-Base, London, United Kingdom.
¹¹ Department of Pediatrics, Boston University School of Medicine, Boston, MA.
¹² Division of Prevention Care and Treatment, Office of HIV/AIDS, United States Agency for International Development (USAID), Washington, DC.
¹³ Global HIV, Hepatitis and STIs Programme, World Health Organization, Geneva, Switzerland.
¹⁴ Department of Pharmacy, Research Institute, University of Liverpool, United Kingdom; and.
¹⁵ Ezintsha, Wits Reproductive Health Sciences, University of Witwatersrand, South Africa.

PMID: 33298793
DOI: 10.1097/QAI.0000000000002597

Enhanced and Timely Investigation of ARVs for Use in Pregnant Women

Elaine J Abrams et al. J Acquir Immune Defic Syndr. 2021.

. 2021 Apr 15;86(5):607-615.

doi: 10.1097/QAI.0000000000002597.

Authors

Affiliations

¹ ICAP at Columbia University, Mailman School of Public Health, Columbia University, New York, NY.
² Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.
³ Research Program, Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC.
⁴ HIV and Sexual Health Clinic, Chelsea and Westminster Hospital NHS Foundation Trust and LSHTM London, London, United Kingdom.
⁵ Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA.
⁶ Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA.
⁷ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
⁸ Radboud University Medical Center, and HIV Institute, Nijmegen, the Netherlands.
⁹ Division of Antiviral Products, US Food and Drug Administration (FDA), Silver Spring, MD.
¹⁰ HIV i-Base, London, United Kingdom.
¹¹ Department of Pediatrics, Boston University School of Medicine, Boston, MA.
¹² Division of Prevention Care and Treatment, Office of HIV/AIDS, United States Agency for International Development (USAID), Washington, DC.
¹³ Global HIV, Hepatitis and STIs Programme, World Health Organization, Geneva, Switzerland.
¹⁴ Department of Pharmacy, Research Institute, University of Liverpool, United Kingdom; and.
¹⁵ Ezintsha, Wits Reproductive Health Sciences, University of Witwatersrand, South Africa.

PMID: 33298793
DOI: 10.1097/QAI.0000000000002597

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 group meeting, December 10-12, 2018, in Geneva, Switzerland.

Methods: The group, comprised of clinicians, scientists, HIV program 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 ARVs 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 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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Conflict of interest statement

E.J.A. and L.M.M. participated in ViiV Dolutegravir Neural Tube Defect Advisory Board (no honorarium); A.P. has been an advisor to Merck Inc, Gilead Sciences, ViiV, and Janssen; S.K. has received research support from Janssen, Merck, Gilead, and ViiV and provided advice to Merck and ViiV; W.D.F.V. has received drug donations from ViiV and Gilead and participated in the Dolutegravir Neural Tube Defect Advisory Board and received honoraria for talks and board membership for Gilead, Viiv, Mylan, Merk, Adcock-Ingram, Aspen, Abbott, Roche, and J&J; and M.M. has received research support from Merck, Gilead, and ViiV. The other authors have no funding or conflicts of interest to disclose.

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References

1. UNAIDS. Start Free Stay Free AIDS Free. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS; 2019. Available at: https://www.unaids.org/sites/default/files/media_asset/start-free-stay-f... . Access November 8, 2020.
1. WHO. Guideline on When to Start Antiretroviral Therapy and on Pre-exposure Prophylaxis for HIV. Geneva, Switzerland: World Health Organization; 2015. Available at: https://apps.who.int/iris/bitstream/handle/10665/186275/9789241509565_en... . Access November 8, 2020.
1. Smith DD, Pippen JL, Adesomo AA, et al. Exclusion of pregnant women from clinical trials during the coronavirus disease 2019 pandemic: a review of international registries. Am J Perinatol. 2020;37:792–799.
1. Colbers A, Mirochnick M, Schalkwijk S, et al. Importance of prospective studies in pregnant and breastfeeding women living with human immunodeficiency virus. Clin Infect Dis. 2019;69:1254–1258.
1. PANNA. PANNA Study. 2020. Available at: https://www.pannastudy.com/main/pannastudy . Accessed January 4, 2021.

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[1] UNAIDS. Start Free Stay Free AIDS Free. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS; 2019. Available at: https://www.unaids.org/sites/default/files/media_asset/start-free-stay-f... . Access November 8, 2020.

[2] UNAIDS. Start Free Stay Free AIDS Free. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS; 2019. Available at: https://www.unaids.org/sites/default/files/media_asset/start-free-stay-f... . Access November 8, 2020.

[3] WHO. Guideline on When to Start Antiretroviral Therapy and on Pre-exposure Prophylaxis for HIV. Geneva, Switzerland: World Health Organization; 2015. Available at: https://apps.who.int/iris/bitstream/handle/10665/186275/9789241509565_en... . Access November 8, 2020.

[4] WHO. Guideline on When to Start Antiretroviral Therapy and on Pre-exposure Prophylaxis for HIV. Geneva, Switzerland: World Health Organization; 2015. Available at: https://apps.who.int/iris/bitstream/handle/10665/186275/9789241509565_en... . Access November 8, 2020.

[5] Smith DD, Pippen JL, Adesomo AA, et al. Exclusion of pregnant women from clinical trials during the coronavirus disease 2019 pandemic: a review of international registries. Am J Perinatol. 2020;37:792–799.

[6] Smith DD, Pippen JL, Adesomo AA, et al. Exclusion of pregnant women from clinical trials during the coronavirus disease 2019 pandemic: a review of international registries. Am J Perinatol. 2020;37:792–799.

[7] Colbers A, Mirochnick M, Schalkwijk S, et al. Importance of prospective studies in pregnant and breastfeeding women living with human immunodeficiency virus. Clin Infect Dis. 2019;69:1254–1258.

[8] Colbers A, Mirochnick M, Schalkwijk S, et al. Importance of prospective studies in pregnant and breastfeeding women living with human immunodeficiency virus. Clin Infect Dis. 2019;69:1254–1258.

[9] PANNA. PANNA Study. 2020. Available at: https://www.pannastudy.com/main/pannastudy . Accessed January 4, 2021.

[10] PANNA. PANNA Study. 2020. Available at: https://www.pannastudy.com/main/pannastudy . Accessed January 4, 2021.

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Enhanced and Timely Investigation of ARVs for Use in Pregnant Women

Affiliations

Enhanced and Timely Investigation of ARVs for Use in Pregnant Women

Authors

Affiliations

Abstract

Conflict of interest statement

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