Pharmacokinetics Study on Nevirapine Resistance in Tanzania

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)

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.

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.

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.

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

Muro EP, Fillekes Q, Kisanga ER, L'homme R, Aitken SC, Mariki G, Van der Ven AJ, Dolmans W, Schuurman R, Walker AS, Gibb DM, Burger DM. Intrapartum single-dose carbamazepine reduces nevirapine levels faster and may decrease resistance after a single dose of nevirapine for perinatal HIV prevention. J Acquir Immune Defic Syndr. 2012 Mar 1;59(3):266-73. doi: 10.1097/QAI.0b013e31824234d8.

http://journals.lww.com/jaids/Abstract/2012/03010/Intrapartum_Single_Dose_Carbamazepine_Reduces.7.aspx

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.