Pharmacokinetics Study on Nevirapine Resistance in Tanzania

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: carbamazepine and nevirapine
* Drug: Nevirapine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Carbamazepine<br>An oral dose of 400mg Carbamazepine is added to the 200mg oral dose Nevirapine intake prior delivery | Drug: carbamazepine and nevirapine<br>* Carbamazepine 400mg and Nevirapine 200mg are taken just before delivery during labor.<br>|
| Placebo Comparator: Nevirapine<br>Standard therapy of 200mg Nevirapine oral prior to delivery | Drug: Nevirapine<br>* Nevirapine 200mg is taken prior to delivery during labor.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cord blood will be taken less than 30 minutes after delivery |  | 0 - 30 min after delivery | 
| Blood samples from mother will be taken less than 30 minutes after delivery to measure viral load and CD4 count. |  | 0 - 30 min after delivery | 
| 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) |  | day 6 - 22 after delivery | 
| From all samples plasma nevirapine and if applicable carbamazepine levels will be determined in women and newborns. |  | 0 30 min after delivery - week 3 after delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, mother to child transmission; MTCT, nevirapine resistance, pharmacokinetics, Treatment Naive