HIV Infections
Conditions
Keywords
HIV, mother to child transmission; MTCT, nevirapine resistance, pharmacokinetics, Treatment Naive
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.
Interventions
DRUGcarbamazepine and nevirapine
Carbamazepine 400mg and Nevirapine 200mg are taken just before delivery during labor.
DRUGNevirapine
Nevirapine 200mg is taken prior to delivery during labor.
Sponsors
Radboud University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
Countries
Tanzania
Outcome results
None listed