Pharmacokinetics Study on Nevirapine Resistance in Tanzania

Phase 2

Completed

• Conditions: HIV Infections
• Interventions: Drug: carbamazepine and nevirapine; Drug: Nevirapine

• Registration Number: NCT00294892
• Lead Sponsor: Radboud University Medical Center

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.

Study Timeline

• Study Start: 2006-02
• Study First Submitted: 2006-02-21
• Study First Submitted QC: 2006-02-21
• Study First Posted: 2006-02-22
• Primary Completion: 2009-09
• Study Completion: 2010-06
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-26
• Last Update Posted: 2020-11-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 144

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Carbamazepine	carbamazepine and nevirapine	An oral dose of 400mg Carbamazepine is added to the 200mg oral dose Nevirapine intake prior delivery
Nevirapine	Nevirapine	Standard therapy of 200mg Nevirapine oral prior to delivery

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Kilimanjaro Christian Medical College; 🇹🇿 Moshi, Tanzania