Pharmacokinetics Study on Nevirapine Resistance in Tanzania

Condition(s) targeted: HIV Infections

Intervention: carbamazepine and nevirapine (Drug); Nevirapine (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Radboud University

Official(s) and/or principal investigator(s):
David M. Burger, Dr., Principal Investigator, Affiliation: Radboud University (RUNMC)

Overall contact:
Eva P. Muro, PhamD, Phone: +255 748468553, Email: muroeva123@yahoo.com

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.

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 design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Pharmacokinetics Study

Primary outcome:

Cord blood will be taken less than 30 minutes after delivery

Blood samples from mother will be taken less than 30 minutes after delivery to measure viral load and CD4 count.

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)

From all samples plasma nevirapine and if applicable carbamazepine levels will be determined in women and newborns.

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.

Minimum age: 18 Years. Maximum age: 40 Years. Gender(s): Female.

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

Eva P. Muro, PhamD, Phone: +255 748468553, Email: muroeva123@yahoo.com

Kilimanjaro Christian Medical College, Moshi, Tanzania; Recruiting
W. Schimana, MD, Sub-Investigator
O. Oneko, MD, Sub-Investigator

Starting date: February 2006
Ending date: December 2009
Last updated: July 21, 2009