Pharmacokinetics Study on Nevirapine Resistance in Tanzania

HIV Infections Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00294892
• Other study ID #: VITA1
• Status: Completed
• Phase: Phase 2
• Start date: February 2006
• Est. completion date: June 2010

Study information

• Verified date: November 2020
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 144
• Est. completion date: June 2010
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• carbamazepine and nevirapine
Carbamazepine 400mg and Nevirapine 200mg are taken just before delivery during labor.
• Nevirapine
Nevirapine 200mg is taken prior to delivery during labor.

Locations

Country	Name	City	State
Tanzania	Kilimanjaro Christian Medical College	Moshi

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Tanzania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cord blood will be taken less than 30 minutes after delivery		0 - 30 min after delivery
Primary	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
Primary	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
Primary	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

External Links

•   J Acquir Immune Defic Syndr. 2012 Mar 1;59(3):266-73. Intrapartum single-dose carbamazepine reduces nevirapine levels faster and may decrease resistance after a single dose of nevirapine for perinatal HIV prevention.