Clinical trial NCT00294892: Pharmacokinetics Study on Nevirapine Resistance in Tanzania
Official title: The Effect of Single Dose Carbamazepine on the Pharmacokinetics of Single Dose Nevirapine (Viramune, NVP) and Development of NVP Resistance, PMTCT Program of Moshi, Tanzania (VITA1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: HIV
mother to child transmission; MTCT
nevirapine resistance
pharmacokinetics
Treatment Naive
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2006-02-22
Enrollment: 144
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary

* pharmacokinetics of single dose nevirapine
* the effect of single dose carbamazepine on the pk of single dose nevirapine
* resistance against nevirapine before and after.
* follow-up on HIV status newborns
* relation between nevirapine levels in cord blood and plasma

Secondary

\* safety of single dose nevirapine and nevirapine/carbamazepine

Hypothesis:

Single dose carbamazepine decreases development of resistance to nevirapine in HIV positive pregnant Tanzanian women by decreasing nevirapine half-life.

Detailed description: Without the use of preventative measures, the risk of mother-to-child transmission (MTCT) of HIV-1 is estimated to vary between 25 and 48%. The regimen of single dose of nevirapine to the mother just before delivery and a single dose of nevirapine to the newborn within 24 - 72 hours after birth reduces the risk of MTCT by 50%, is affordable in many situations and is therefore standard of care in many African countries, like Tanzania. Recent studies, however, have shown that this single dose to the mother can induce the occurrence of nevirapine resistance in a large number of mothers. The mechanism of occurrence of nevirapine resistance already after a single dose is most likely related to the long elimination half-life of the drug. The subtherapeutic plasma levels present the perfect environment for the occurrence of resistance as the concentrations are subinhibitory for several days.

Eligibility criteria: Inclusion Criteria:

* HIV infected
* antiretroviral naive
* not intending to relocate out of area during study
* willing to adhere to follow up scheme
* ability and willing to give written consent
* pregnant between 18 and 40 years
* willing and able to regularly attend the Antenatal clinic

Exclusion Criteria:

* serious illness that requires systemic treatment or hospitalization
* any condition that would compromise subject's ability to participate
* previously treated for HIV with antiretroviral agents, including single dose nevirapine used for MTCT
* inability to understand the nature and extent of the trial and procedures

Primary outcomes:
measure: Cord blood will be taken less than 30 minutes after delivery
timeFrame: 0 - 30 min after delivery
measure: Blood samples from mother will be taken less than 30 minutes after delivery to measure viral load and CD4 count.
timeFrame: 0 - 30 min after delivery
measure: Blood samples will be drawn from mother and child at week 1 (day 6-8), week 2 (day 13-15) and week 3 (day 20-22)
timeFrame: day 6 - 22 after delivery
measure: From all samples plasma nevirapine and if applicable carbamazepine levels will be determined in women and newborns.
timeFrame: 0 30 min after delivery - week 3 after delivery
Secondary outcomes:
Other outcomes:
Locations:
city: Moshi
country: Tanzania
facility: Kilimanjaro Christian Medical College
Study officials:
affiliation: Radboud University (RUNMC)
name: David M. Burger, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Muro EP, Fillekes Q, Kisanga ER, L'homme R, Aitken SC, Mariki G, Van der Ven AJ, Dolmans W, Schuurman R, Walker AS, Gibb DM, Burger DM. Intrapartum single-dose carbamazepine reduces nevirapine levels faster and may decrease resistance after a single dose of nevirapine for perinatal HIV prevention. J Acquir Immune Defic Syndr. 2012 Mar 1;59(3):266-73. doi: 10.1097/QAI.0b013e31824234d8.