A single dose of 600mg of tenofovir
disproxil fumurate (TDF) given to a pregnant HIV-infected women during labour, followed
by a daily dose of 6mg/kg to her newborn, is an effective and simple regimen
offering an important alternative to nevirapine for prevention of
mother-to-child transmission, Dr Karin Nielsen-Saines reported on behalf of the
HPTN 057 study group.
HPTN 057 is a phase 1 trial
looking at the pharmacokinetics (PK) of TDF dosing in pregnant HIV-infected
women during labour, and in their newborns, in Malawi and Brazil.Limited information exists on the
pharmacokinetics of TDF in this population.
TDF was approved for adults
in 2001 and is a preferred nucleoside reverse transcriptase inhibitor (NRTI) in international guidelines.
A regimen of 600mg of tenofovir
was given to the woman at the start of labour or four hours before a caesarean
section, with daily doses of 6mg/kg TDF suspension given to the
newborn for seven days.
The PK goal was achieved: to
keep infant tenofovir concentration throughout the first week above 50ng/mL (the same as the mean trough TDF concentration in non-pregnant adults).
Among the 33 mother-infant
pairs (16 in Malawi and 17 in Brazil), median delivery was 4.5 hours (0.6-11.4
hours) after dosing.
Dr Nielsen-Saines noted that,
while there was no advantage to giving a higher dose (900 mg), timing of the
dose was critical.
The mean maternal TDF
concentration at delivery was 108ng/mL. Mean cord-blood TDF concentration
was 61 ng/mL with 77% (24/31) over 50ng/mL.
Dr Nielsen-Saines stressed
that it was important to give the newborn the first dose as soon as possible
after delivery since the maternal dose may not always cross over into the
Post-dose concentration in
infants was over 50ng/mL in 90.3% (28/31), 96.4% (27/28) and 73.3% (22/30) 24
hours after the first, fourth and seventh doses, respectively. All infant TDF
concentration was over 30ng/mL.
This dosing was well tolerated in
all women and their newborns. There were no severe or life-threatening events
A number of protease
inhibitors are approved for use in children. In the US, six are
available in a liquid formulation, with three approved for use in children under
three. In resource-poor settings, the options are much more limited.
Fosamprenavir (Telzir, Levixa) is a protease
inhibitor developed by Glaxo SmithKline and now marketed by Viiv Healthcare. It
is less widely used than other protease inhibitors in adults.
Dr Jorg Sievers, on behalf
of the APV20002 study, reported data
from a phase II safety and efficacy study of a paediatric formulation of
fosamprenavir combined with ritonavir.
This prospective open-label,
multi-centre, 48-week cohort study looked at the PK, safety and antiviral
activity of fosamprenavir and ritonavir in two cohorts of HIV-infected children, both protease-inhibitor naive and experienced, aged from six months to under two years (cohort 1) and
from four weeks to under six months (cohort 2). The majority of infants and
children in this study were located in Mexico and South Africa.
Out of a total of 59 infants, 78%
were exposed to fosamprenavir for over 48 weeks. In total, 64% and 58% in cohorts 1 and 2,
respectively, achieved undetectable viral load at 48 weeks. Nine infants had virological
Of the twenty-two who
experienced serious adverse events, three were considered drug-related and
three died after these events.
Dr Sievers concluded that
fosamprenavir/ritonavir dosing regimens in cohort 1 resulted in plasma APV exposure comparable to
that achieved in adult approved regimens. While the minimal APV exposure was
lower in cohort 2, the clinical outcomes were nonetheless comparable.
Overall safety, he added, was
similar to that seen in older children and adults.
This combination provides another
option for treatment with a PI for children in the US. The US Food and Drug
Administration (FDA) has approved its use in children from four weeks of age.