Pharmacokinetics Study on Nevirapine Resistance in Tanzania

Radboud University Medical Center

Status and phase: Completed; Phase 2

Conditions: HIV Infections

Treatments: Drug: carbamazepine and nevirapine; Drug: Nevirapine

Study type: Interventional

Funder types: Other

Identifiers

NCT00294892

VITA1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 144 patients

Sex: Female

Ages: 18 to 40 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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144 participants in 2 patient groups, including a placebo group

Carbamazepine

Active Comparator group

Description:

An oral dose of 400mg Carbamazepine is added to the 200mg oral dose Nevirapine intake prior delivery

Treatment:

Drug: carbamazepine and nevirapine

Nevirapine

Placebo Comparator group

Description:

Standard therapy of 200mg Nevirapine oral prior to delivery

Treatment:

Drug: Nevirapine