Rifampicin was also shown to have no
significant effect of on efavirenz Cmin levels in pregnant women and
their infants, according to the preliminary results from the TSHEPISO efavirenz
pharmacokinetic substudy presented at AIDS 2012.
The combined effect of pregnancy and rifampicin-containing
TB treatment on efavirenz Cmin, virologic suppression and prevention
of maternal-to-child transmission of HIV (PMTCT) has not been studied before.
TSHEPISO is a prospective cohort study
among HIV-infected pregnant women with TB (n=250 cases) and without TB (n=500
controls), currently enrolling in Soweto, South Africa. Women (n=150) with and
without TB, on efavirenz-containing ARV will enrol in the substudy, along with
The preliminary results from 76 women and
70 infants in the substudy to date show that the estimated efavirenz Cmin
among women pre/intrapartum and postpartum were not significantly different.
The model, which also took weight and CYP2B6 genotype (the enzyme central to the
metabolism of efavirenz) into account, was unable to show a significant effect
of rifampicin on efavirenz Cmin (except among slow efavirenz metabolizers).
The median efavirenz Cmin of the
40 pre/intrapartum women taking rifampicin was 1.76 (IQR: 0.89-3.13), with
29.6% with an efavirenz Cmin of less than 1mg/l. In the 46 women not taking
rifampicin six weeks postpartum, the median efavirenz Cmin was 1.52
(IQR: 1.14-2.02) with 17.1% with an efavirenz Cmin of less than
Despite the 29.6% of women on rifampicin
with Cmin less than 1 mg/l, the viral load was suppressed in most
women taking efavirenz for three months or more at the time of delivery. There
were no cases of mother-to-child transmission of HIV.
The effect of genotype CYP2B6 showed that
56.3% with extensive, 5.7% with intermediate, 16.7% with slow and 0% with very
slow efavirenz metabolism had an efavirenz Cmin of less than 1mg/l.
Difference in weight did not prove a
significant factor for EFV Cmin levels in those taking rifampicin or
not taking rifampicin. The median Cmin levels were both 1.91 for
women below and above 60kg in those taking rifampicin, but 20% of those less
than 60kg had a Cmin less than 1mg/l compared to 31.6% in the women
weighing more than 60kg. The median Cmin for women less than 60kg
was 1.33 (IQR: 1.12-1.64, 11.1% with a Cmin less than 1mg/l) and 1.55 (IQR:1.13-2.07,16.7%
with a Cmin less than 1mg/l) in women
not on rifampicin treatment.
Preliminary results also showed that 70% of
TB/HIV co-infected women and 83% of HIV-only infected women had undetectable
viral load counts at delivery, although this difference was not statistically
significant (p=0.24).Of those taking efavirenz for at least 12 weeks at
delivery, 82% of TB/HIV co-infected women and 93% of HIV-only infected women
had undetectable viral loads, although this difference was again statistically
Blood samples taken from infant umbilical
cords in 45 infants showed the median efavirenz Cmin to be 1.15
(IQR: 0.628-1.91, 8.9% with a Cmin less than 1mg/l. Cord and
maternal pre-partum concentrations were highly correlated (r=0.93). However,
the median efavirenz Cmin in infant blood at seven days after birth
was 0.079 (61.4%with a Cmin less than 1mg/l). However, quantifiable
values were related to larger cord-blood concentrations.