Pharmacokinetics of Antiretroviral Agents in HIV-infected Pregnant Women.

NCT00825929 | Recruiting

• 1 other identifier: UMCN-AKF 08.02
• Study Type: observational
• Target: 176
• Locations: 7 countries
• Sites: 21

Brief Summary

Due to the potential for pregnancy-induced changes in the pharmacokinetics of medication, one cannot assume that the currently licensed doses of the medication to be tested under this protocol lead to adequate exposure in an HIV-infected pregnant woman. For the agents under study no or limited pharmacokinetic data during pregnancy are available. As the changes in pharmacokinetics during pregnancy are most prominent in the third trimester a pharmacokinetic curve will be recorded in the third trimester after attaining steady state.

Conditions

HIV Infections

Keywords

pharmacokinetics; pregnancy; antiretrovirals; neonates; HIV; treatment experienced

Outcome Measures

Primary Outcomes (1)

• Plasma concentrations of the compounds during pregnancy compared to the concentrations after delivery

  PK curve in Week 33 of pregnancy and 4-6 weeks after delivery

Secondary Outcomes (3)

• Pharmacokinetics in the neonate, in case of post-exposure prophylaxis with one of the agents under study.

  Week 1, 3 and between 4 and 6

• Safety of antiretrovirals during pregnancy

  GA Week 33 until end of trial

• viral load response and prevention of mother to child transmission of the virus

  GA Week 3 and at delivery

Study Arms (1)

1

Treated with one of the antiretroviral agents under study, PK parameters during pregnancy will be compared with PK parameters after pregnancy (within the same woman)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

HIV-infected pregnant women using at least one of the following antiretroverial agents: Etravirine, Intelence, TMC125; Emtricitabine, Emtriva or FTC; Tenofovir, Viread, TDF; Atazanavir, Reyataz; Fosamprenavir, Telzir, FPV; Darunavir, Prezista, TMC114; Tipranavir, Aptivus, TPV; Indinavir, Crixivan; abacavir; raltegravir, Isentress; Enfuvirtide, Fuzeon; Maraviroc, Celsentri; dolutegravir; elvitegravir/cobicistat; rilpivirine, TAF, darunavir/cobicistat; doravirine; bictegravir; cabotegravir/rilpivirine LA

You may qualify if:

• HIV-infected as documented by positive HIV antibody test and confirmed by an antigen test.
• Subject is at least 18 years of age at screening.
• Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
• Treated with a cART regimen containing at least one agent which is mentioned in Appendix 1; this agent has been taken for at least 2 weeks before the day of first PK curve evaluation.
• Subject is pregnant
• Subject is able to adhere to food intake recommendations, if applicable.

You may not qualify if:

• Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
• Inability to understand the nature and extent of the study and the procedures required.
• Presence of grade III/IV anemia (i.e. Hb \<4.6 mmol/L or \<7.4 g/dL).
• Using oral cabotegravir/rilpivirine.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• PENTA Foundation: collaborator
• Merck Sharp & Dohme LLC: collaborator
• Bristol-Myers Squibb: collaborator
• Janssen Pharmaceutica: collaborator
• ViiV Healthcare: collaborator
• Gilead Sciences: collaborator

Study Sites (21)

Saint-Pierre University Hospital; Department of Infectious Diseases

Brussels, Belgium

RECRUITING

CHARITÉ Berlin

Berlin, Germany

RECRUITING

University of Bonn

Bonn, Germany

RECRUITING

University of Cologne

Cologne, Germany

RECRUITING

Johann Wolfgang Goethe-Universität

Frankfurt am Main, Germany

RECRUITING

University München

München, Germany

RECRUITING

Mater Hospital and UCD

Dublin, Ireland

RECRUITING

St James's Hospital Dublin

Dublin, Ireland

RECRUITING

IRCSS

Rome, Italy

COMPLETED

AMC

Amsterdam, Netherlands

COMPLETED

Radboud University Nijmegen Medical Centre

Nijmegen, Netherlands

RECRUITING

Erasmus Medical Center Rotterdam

Rotterdam, Netherlands

RECRUITING

St Elisabeth hospital

Tilburg, Netherlands

RECRUITING

Hospital Universitari Germans Trias i Pujol, Badalona

Badalona, Spain

RECRUITING

Hospital Universitario Virgen de las Nieves Granada; Médico Adjunto del Servicio de Medicina Interna

Granada, Spain

RECRUITING

Brighton and Sussex University Hospitals NHS Trust

Brighton, United Kingdom

RECRUITING

C&W Hospital, London

London, United Kingdom

RECRUITING

North Middlesex Hospital

London, United Kingdom

COMPLETED

St Mary's Hospital, London

London, United Kingdom

RECRUITING

St Thomas Hospital

London, United Kingdom

WITHDRAWN

St. George's Hospital, London

London, United Kingdom

COMPLETED

Related Publications (12)

• Colbers AP, Hawkins DA, Gingelmaier A, Kabeya K, Rockstroh JK, Wyen C, Weizsacker K, Sadiq ST, Ivanovic J, Giaquinto C, Taylor GP, Molto J, Burger DM; PANNA network. The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1-infected pregnant women. AIDS. 2013 Mar 13;27(5):739-48. doi: 10.1097/QAD.0b013e32835c208b.

  PMID: 23169329 RESULT

• Colbers A, Gingelmaier A, van der Ende M, Rijnders B, Burger D. Pharmacokinetics, safety and transplacental passage of rilpivirine in pregnancy: two cases. AIDS. 2014 Jan 14;28(2):288-90. doi: 10.1097/QAD.0000000000000100. No abstract available.

  PMID: 24413315 RESULT

• Bollen P, Freriksen J, Konopnicki D, Weizsacker K, Hidalgo Tenorio C, Molto J, Taylor G, Alba-Alejandre I, van Crevel R, Colbers A, Burger D; Pharmacokinetics of ANtiretroviral agents in HIV-infected pregNAnt women Network. The Effect of Pregnancy on the Pharmacokinetics of Total and Unbound Dolutegravir and Its Main Metabolite in Women Living With Human Immunodeficiency Virus. Clin Infect Dis. 2021 Jan 23;72(1):121-127. doi: 10.1093/cid/ciaa006.

  PMID: 32103260 RESULT

• Overbeek JK, van Erp NP, Burger DM, den Broeder AA, Koolen SLW, Huitema ADR, Ter Heine R. Population Pharmacokinetics of Cobicistat and its Effect on the Pharmacokinetics of the Anticancer Drug Olaparib. Clin Pharmacokinet. 2025 Mar;64(3):425-435. doi: 10.1007/s40262-025-01480-w. Epub 2025 Feb 5.

  PMID: 39909979 DERIVED

• Bukkems V, Necsoi C, Tenorio CH, Garcia C, Rockstroh J, Schwarze-Zander C, Lambert JS, Burger D, Konopnicki D, Colbers A. Clinically Significant Lower Elvitegravir Exposure During the Third Trimester of Pregnant Patients Living With Human Immunodeficiency Virus: Data From the Pharmacokinetics of ANtiretroviral agents in HIV-infected pregNAnt women (PANNA) Network. Clin Infect Dis. 2020 Dec 17;71(10):e714-e717. doi: 10.1093/cid/ciaa488.

  PMID: 32330231 DERIVED

• Kreitchmann R, Schalkwijk S, Best B, Wang J, Colbers A, Stek A, Shapiro D, Cressey T, Mirochnick M, Burger D. Efavirenz pharmacokinetics during pregnancy and infant washout. Antivir Ther. 2019;24(2):95-103. doi: 10.3851/IMP3283.

  PMID: 30530925 DERIVED

• Schalkwijk S, Colbers A, Konopnicki D, Gingelmaier A, Lambert J, van der Ende M, Molto J, Burger D; Pharmacokinetics of newly developed antiretroviral agents in HIV-infected pregnant women (PANNA) Network. Lowered Rilpivirine Exposure During the Third Trimester of Pregnancy in Human Immunodeficiency Virus Type 1-Infected Women. Clin Infect Dis. 2017 Oct 15;65(8):1335-1341. doi: 10.1093/cid/cix534.

  PMID: 28595298 DERIVED

• Mulligan N, Schalkwijk S, Best BM, Colbers A, Wang J, Capparelli EV, Molto J, Stek AM, Taylor G, Smith E, Hidalgo Tenorio C, Chakhtoura N, van Kasteren M, Fletcher CV, Mirochnick M, Burger D. Etravirine Pharmacokinetics in HIV-Infected Pregnant Women. Front Pharmacol. 2016 Aug 4;7:239. doi: 10.3389/fphar.2016.00239. eCollection 2016.

  PMID: 27540363 DERIVED

• Colbers A, Best B, Schalkwijk S, Wang J, Stek A, Hidalgo Tenorio C, Hawkins D, Taylor G, Kreitchmann R, Burchett S, Haberl A, Kabeya K, van Kasteren M, Smith E, Capparelli E, Burger D, Mirochnick M; PANNA Network and the IMPAACT 1026 Study Team. Maraviroc Pharmacokinetics in HIV-1-Infected Pregnant Women. Clin Infect Dis. 2015 Nov 15;61(10):1582-9. doi: 10.1093/cid/civ587. Epub 2015 Jul 22.

  PMID: 26202768 DERIVED

• Blonk MI, Colbers AP, Hidalgo-Tenorio C, Kabeya K, Weizsacker K, Haberl AE, Molto J, Hawkins DA, van der Ende ME, Gingelmaier A, Taylor GP, Ivanovic J, Giaquinto C, Burger DM; Pharmacokinetics of Newly Developed Antiretroviral Agents in HIV-Infected Pregnant Women PANNA Network; PANNA Network. Raltegravir in HIV-1-Infected Pregnant Women: Pharmacokinetics, Safety, and Efficacy. Clin Infect Dis. 2015 Sep 1;61(5):809-16. doi: 10.1093/cid/civ366. Epub 2015 May 5.

  PMID: 25944344 DERIVED

• Colbers A, Molto J, Ivanovic J, Kabeya K, Hawkins D, Gingelmaier A, Taylor G, Weizsacker K, Sadiq ST, Van der Ende M, Giaquinto C, Burger D; PANNA Network. Pharmacokinetics of total and unbound darunavir in HIV-1-infected pregnant women. J Antimicrob Chemother. 2015 Feb;70(2):534-42. doi: 10.1093/jac/dku400. Epub 2014 Oct 17.

  PMID: 25326090 DERIVED

• Colbers A, Hawkins D, Hidalgo-Tenorio C, van der Ende M, Gingelmaier A, Weizsacker K, Kabeya K, Taylor G, Rockstroh J, Lambert J, Molto J, Wyen C, Sadiq ST, Ivanovic J, Giaquinto C, Burger D; PANNA network. Atazanavir exposure is effective during pregnancy regardless of tenofovir use. Antivir Ther. 2015;20(1):57-64. doi: 10.3851/IMP2820. Epub 2014 Jul 3.

  PMID: 24992294 DERIVED

Related Links

• PANNA study website

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples will be collected in Week 33 of the pregnancy and at 4-6 weeks after delivery. At the following time points T=0 (prior to dosing), and T=1, 2, 3, 4, 6, 8, 12 and 24h (24h sample only in case of QD regimen) post-dosing (8 or 9 samples). In case the infant needs post-exposure prophylaxis with at least one of the agents sparse PK sampling is optional. If the mother decides to breastfeed, also breast milk samples at 2, 4, 6, 12 and 24 hours after dosing will be collected on the postpartum PK day. For CAB/RPV: Maternal PK curve after the injection from 24 weeks gestational age and after first or second injection postpartum: one sample prior to injection, and at day 3, 7, 28 and 56 (in case of 2 monthly injections). If the mother decides to breastfeed, also breast milk samples at the same postpartum timepoints and one infant blood sample (extra consent) will be collected.

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• David M Burger, PharmD PhD

  Radboud University Medical Centre Nijmegen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David M Burger, PharmD PhD

CONTACT

++31 24 3616405; david.burger@radboudumc.nl

Wendy van der Wekken, MSc

CONTACT

Study Design

• Study Type: observational
• Observational Model: CASE CROSSOVER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2009
• First Posted: January 21, 2009
• Study Start: February 1, 2009
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 13, 2025

Record last verified: 2025-01

Locations

ES (2); GB (6); IT (1); DE (5); NL (4); IE (2); BE (1)