PANNA study
The PANNA study is a study with the purpose of collecting pharmacokinetic data (PK curves) in pregnant HIV-infected women using newly developed antiretroviral agents.
The primary objective of this study is to describe the pharmacokinetics of antiretroviral agents during pregnancy for which no or only limited pharmacokinetic data during pregnancy are available. Pharmacokinetic curves will be collected in the 3rd trimester of pregnant HIV-infected women and at 4-6 weeks post-partum. In addition, the pharmacokinetics will be determined in the infant as well, in case of post-exposure prophylaxis with one of the agents tested.
The secondary objective of this study is to describe the safety of the antiretroviral agents during pregnancy and the efficacy in terms of viral load response of the mother and prevention of mother-to-child transmission.
Rationale
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.
Antiretroviral agents under study
The following agents are being studied:
- Efavirenz, Stocrin®, EFV(NNRTI) (UK only)
- Etravirine, Intelence®, TMC125 (NNRTI)
- Emtricitabine, Emtriva® or FTC (NRTI)
- Tenofovir, Viread®, TDF (NtRTI)
- Atazanavir, Reyataz® (PI)
- Darunavir, Prezista® (PI)
- Fosamprenavir, Telzir®, FPV (PI)
- Tipranavir, Aptivus®, TPV (PI)
- Indinavir, Crixivan® (PI)
- Raltegravir, Isentress® (integrase inhib)
- Enfuvirtide, Fuzeon® (entry inhibitor)
- Maraviroc, Celsentri® (entry inhibitor)
If new compounds are registered, they can be added to the list of compounds under study by an amendment. In that case, no new protocol has to be written.
Procedure pharmacokinetics
In the third trimester and at 4-6 weeks post partum blood samples (6 mL) will be taken for measurement of plasma drug concentration on T=0 (prior to dosing), and T= 0.5, 1, 2, 3, 4, 6, 8, 12 and 24h (24h sample only in case of QD regimen) post-dosing (9 or 10 samples per curve). The women will be admitted to the hospital during one day (12 hours admission). At delivery, a cord blood sample will be taken, if possible. In case the infant needs post-exposure prophylaxis with at least one of the agents, sparse PK sampling is optional.
Efficacy and safety
Viral load and CD4 count will be determined at screening and on the day of PK evaluation. The HIV status of the infant(s) will be collected. Biochemistry and haematology evaluation, urinalysis, at screening, and during the day of PK evaluation. Body weight at the day of PK evaluation. Adverse events will be collected from screening until last assessment.
Number of subjects planned
Per antiretroviral agent 16 subjects are planned.
Results presented/published
Preliminary data raltegravir, poster presented at the 12th International Workshop on Clinical Pharmacology of HIV Therapy, Miami, FL raltegravir_poster_PKworkshop_2011.
