The Effect of Phenytoin on the Pharmacokinetics of Nevirapine and the Development of Nevirapine Resistance

• Status: Completed
• Trial end date: 2012-09-01
• Target enrollment: 0
• Participant gender: Female

Summary

The primary objective of this two-phase trial is as follows:

• To determine the elimination half-life of NVP in HIV positive pregnant women receiving it as a single dose in labour in addition to the ZDV and 3TC with or without seven days phenytoin (pilot PK phase)

• To determine NVP resistance in HIV positive pregnant women receiving it as a single dose in labour in addition to ZDV and 3TC with or without seven days phenytoin (main trial phase)

The secondary objectives of this two-phase trial are as follows:

• To determine the safety of single dose nevirapine with seven days phenytoin as a part of ARV prophylaxis for PMTCT vs. single dose of nevirapine without phenytoin as a part of ARV prophylaxis for PMTCT

• To determine the HIV status of the infant

• To determine the safety of the ARV prophylaxis for PMTCT with seven days of phenytoin on the newborn

Hypothesis: phenytoin reduces the elimination half life of SD NVP and thereby decreases development of resistance to NVP in HIV positive pregnant Tanzanian and Zambian women.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Radboud University
• Treatments: Nevirapine; Phenytoin

Criteria

Inclusion Criteria:

• HIV-infected as documented by positive HIV antibody test

• Antiretroviral naïve

• Starting ARV prophylaxis from 28th weeks of gestation or at least 4 weeks before delivery

• Not intending to relocate out of the area for the duration of study participation

• Willingness of subject to adhere to follow up schedule (note: this is more intensive for the pilot PK phase)

• Ability and willingness of subject to give written consent

• Pregnant women aged 18 years and above

• Willing and able to regularly attend the antenatal clinic

Exclusion Criteria:

• Serious illness that requires systemic treatment or hospitalization

• Use of concomitant medication, which interferes with the ARV prophylaxis for PMTCT or phenytoin

• Any condition that in the opinion of the investigator would compromise the subjects' ability to participate in the study

• Previously treated for HIV infection with antiretroviral agents, including ARV prophylaxis for PMTCT

• Inability to understand the nature and extent of the trial and the procedures required

• CD4 count <350 cells/µl because such a patient is eligible for HAART