A Single-arm, Open-label, Study to Assess the Pharmacokinetics of Darunavir/Ritonavir, Etravirine, and Rilpivirine in HIV-1 Infected Pregnant Women

• To assess the influence of pregnancy on the pharmacokinetics of darunavir/ritonavir (darunavir/r) and/or etravirine and rilpivirine during the second and third trimesters of gestation, as well as postpartum [ Time Frame: During the second and third trimesters of gestation, as well as postpartum ] [ Designated as safety issue: No ]
  

• Changes in anti-viral activity, safety and tolerability antiretroviral regimens during gestation and postpartum; compare concentrations between serum and cord blood; pregnancy outcome of darunavir/r and/or etravirine and rilpivirine [ Time Frame: During gestation and postpartum. ] [ Designated as safety issue: No ]
  

There are many biological changes that occur during pregnancy, some of which may affect the way HIV medications are absorbed, distributed and removed within the body. Some medications have been used for HIV treatment during pregnancy, but little is known about how pregnancy affects the class of drugs being looked at in this study. To participate in this study, patients must be receiving 600mg of TMC114 (darunavir) taken with 100mg ritonavir twice daily and/or 200mg of TMC125 (etravirine) twice daily, or 800mg of TMC114 (darunavir) or 25mg of TMC278 (rilpivirine) plus additional antiretroviral drugs needed to construct an active antiretroviral regimen. Darunavir and ritonavir, etravirine, or rilpivirine will be supplied to study participants. Darunavir and ritonavir are human immunodeficiency virus (HIV) protease inhibitors (PIs); etravirine and rilpivirine are non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV. Twelve-hour or twenty four-hour blood sampling will be done for each patient at each of three study visits: Visit 4 (2nd trimester), Visit 5 (3rd trimester), and Visit 8 (6-12 weeks postpartum). Eight blood draws will be taken during each visit: One prior to intake of study medication, and one for each of seven post-dose sampling time-points (hours 1, 2, 3, 4, 6, 9 and 12).

The study is designed primarily to look at the pharmacokinetics of darunavir/ritonavir (darunavir/r) and/or etravirine or rilpivirine during the second and third trimesters of gestation, as well as postpartum. Pharmacokinetics measures how the body absorbs, distributes and excretes medication. The study will also look for any changes in anti-viral activity during pregnancy, and the postpartum period. It will observe any safety and tolerability of the medications used by the mother, and will measure the level of darunavir/r and/or etravirine or rilpivirine in the newborn's cord blood at the time of delivery; outcomes for both mother and child will be assessed as well. During the treatment period, patients will be seen at regular visits during which the investigator will assess the patient's medical condition, any Adverse Events and study drug compliance. Laboratory evaluations for efficacy and safety will be done at regular visits as well as blood pressure monitoring. Up to forty-eight (48) HIV positive pregnant women will participate in this study. Study enrollment will be closed once 12 evaluable patients taking darunavir/ritonavir once daily, 12 evaluable patients taking darunavir/ritonavir twice daily, 12 evaluable patients taking etravirine and 12 evaluable patients taking rilpivirine have been enrolled. The study will be conducted at approximately 14 research centers in the United States and 1 in Puerto Rico. In order to participate, patients must be pregnant for 13-24 weeks. The primary purpose (or outcome) of the study is to assess the influence of pregnancy on the pharmacokinetics of darunavir/ritonavir (darunavir/r) and/or etravirine or rilpivirine during the second and third trimesters of gestation, as well as postpartum. Information collected in this study may be analyzed after either 12 patients on darunavir/r once daily or 12 patients on darunavir/r twice daily or 12 patients on etravirine or 12 patients on rilpivirine have completed their last visit. A final analysis will be completed after all 48 patients have completed their last visit. Darunavir: One 600 mg or two 300 mg tablets taken twice daily by mouth (two or four tablets a day total). Ritonavir: 100mg tablet taken twice daily by mouth (two tablets a day total), together with darunavir. Darunavir: Two 400 mg tablets taken once daily by mouth (two tablets a day total). Ritonavir: 100mg tablet taken once daily by mouth (one tablet a day total), together with darunavir. Etravirine: Two 100 mg tablets taken twice daily by mouth (four tablets a day total). Rilpivirine: One 25mg tablet taken once daily by mouth (one tablet a day total). Study medication will be given from the baseline visit (second pregnancy trimester) until Visit 8 (up to 12 weeks after delivery).