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| Name | Class |
|---|---|
| PENTA Foundation | NETWORK |
| Merck Sharp & Dohme LLC | INDUSTRY |
| Bristol-Myers Squibb | INDUSTRY |
| Janssen Pharmaceutica |
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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.
The following agents will be studied:
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 long acting injectables
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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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
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| David M Burger, PharmD PhD | Contact | ++31 24 3616405 | david.burger@radboudumc.nl | |
| Wendy van der Wekken, MSc | Contact |
| Name | Affiliation | Role |
|---|---|---|
| David M Burger, PharmD PhD | Radboud University Medical Centre Nijmegen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Saint-Pierre University Hospital; Department of Infectious Diseases | Recruiting | Brussels | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23169329 | Result | 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. | |
| 24413315 |
| Label | URL |
|---|---|
| PANNA study website | View source |
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| INDUSTRY |
| ViiV Healthcare | INDUSTRY |
| Gilead Sciences | INDUSTRY |
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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.
| viral load response and prevention of mother to child transmission of the virus | GA Week 3 and at delivery |
| CHARITÉ Berlin | Recruiting | Berlin | Germany |
|
| University of Bonn | Recruiting | Bonn | Germany |
|
| University of Cologne | Recruiting | Cologne | Germany |
|
| Johann Wolfgang Goethe-Universität | Recruiting | Frankfurt am Main | Germany |
|
| University München | Recruiting | München | Germany |
|
| Mater Hospital and UCD | Recruiting | Dublin | Ireland |
|
| St James's Hospital Dublin | Recruiting | Dublin | Ireland |
|
| IRCSS | Completed | Rome | Italy |
| AMC | Completed | Amsterdam | Netherlands |
| Radboud University Nijmegen Medical Centre | Recruiting | Nijmegen | Netherlands |
|
| Erasmus Medical Center Rotterdam | Recruiting | Rotterdam | Netherlands |
|
| St Elisabeth hospital | Recruiting | Tilburg | Netherlands |
|
| Hospital Universitari Germans Trias i Pujol, Badalona | Recruiting | Badalona | Spain |
|
| Hospital Universitario Virgen de las Nieves Granada; Médico Adjunto del Servicio de Medicina Interna | Recruiting | Granada | Spain |
|
| Brighton and Sussex University Hospitals NHS Trust | Recruiting | Brighton | United Kingdom |
|
| C&W Hospital, London | Recruiting | London | United Kingdom |
|
| North Middlesex Hospital | Completed | London | United Kingdom |
| St Mary's Hospital, London | Recruiting | London | United Kingdom |
|
| St Thomas Hospital | Withdrawn | London | United Kingdom |
| St. George's Hospital, London | Completed | London | United Kingdom |
| 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. |
| 32103260 | 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. |
| 39909979 | Derived | 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. |
| 32330231 | 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. |
| 30530925 | 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. |
| 28595298 | 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. |
| 27540363 | 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. |
| 26202768 | 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. |
| 25944344 | 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. |
| 25326090 | 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. |
| 24992294 | 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. |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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