Intravenous (IV)-zidovudine (AZT or ZDV)
during labour and delivery is effective in reducing mother-to-child
transmission (MTCT) among HIV-positive women with virological failure (viral
load at or above 1000 copies/ml), even if on antiretroviral therapy (ART) during pregnancy, according to
an analysis from the French Perinatal Cohort (ANRS-EPF) published in the
advance online edition of Clinical
However, for the majority
(77%) with well-controlled viral load (at or under 400 copies/ml) at delivery
and without obstetrical risk factors (premature rupture of membranes, preterm
delivery, fever or bleeding) IV-zidovudine was not significantly associated
with a lower risk of transmission.
These findings, note the
authors, support recent changes in French and US guidelines to no longer
recommend systematic IV-zidovudine during labour and delivery when viral
load is low and no obstetrical risk factors exist.
Findings from this study – comprising over 11,000 women with HIV, on ART and not breastfeeding, who
delivered at 90 centres throughout France between January 1,1997 and December
30, 2010 – show that without IV-zidovudine overall MTCT rates among women with
virological failure was higher than with, 7.5% and 2.9%, respectively, p = 0.01.
Among newborns given zidovudine
monotherapy the MTCT rate was 10.2%. However, giving newborns zidovudine
+ lamivudine or a protease inhibitor (PI)-based ART regimen eliminated any
difference in transmission rates between mothers who got IV-zidovudine and
those who did not, 4.1% and 4.8%, respectively, p = 0.83.
The availability of ART in
resource-rich settings has dramatically reduced MTCT rates to approximately one
percent. However, the precise role ART plays during pregnancy, labour and
delivery is difficult to determine as transmission can happen at any time
Studies before the era of
ART, showed that most cases of MTCT happened during labour and delivery. So, in 1994, US and French researchers
designing the pivotal trial ACTG076-ANRS024 recommended IV-zidovudine during
labour or caesarean as a link between pre- and post-natal prophylaxis. IV-zidovudine
was then included in guidelines in all resource-rich countries as a component
of preventing MTCT.
With the advent of ART the
benefits of IV-zidovudine have been questioned.
Following previous findings of
data (1997-2004) from this cohort, before ART was recommended for all pregnant
women living with HIV, updated guidelines suggest IV-zidovudine may not be
necessary for women on ART with well-controlled viral load near delivery (not
defined in the 2010 French guidelines and defined in the updated July 2012 US
guidelines as under 400 copies/ml).
The authors looked at the
effect of IV-zidovudine on MTCT according to maternal characteristics, viral
load and obstetric conditions.
There were no specific HIV
treatment and obstetric care recommendations for women included in the cohort.
From 1994, antenatal prophylaxis consisted of zidovudine prophylaxis; from 1997
of dual nucleoside therapy with elective caesarean section (C-section) based on
a risk/benefit evaluation.
ART initially recommended for
pregnant women needing it for their own health was revised in 2004 to include
all pregnant women living with HIV. From 2002, elective caesarean for preventing MTCT was
restricted to women not on ART and with a viral load over 400 copies/ml near
delivery. Up until July 2010 IV-zidovudine and newborn prophylaxis was
The MTCT rate was compared
between women getting IV-zidovudine and those not, analysed according to viral
load at delivery (under 400, 400 to 999, and at or above 1000 copies/ml) and
stratified according to mode of delivery, term of delivery (under or over 37
gestational weeks) and type of post-natal prophylaxis.
For the analysis, CD4 counts
and percentages and plasma viral load were obtained closest to the time of
delivery and not more than seven days after delivery.
Of the 11,538 women included
in the analysis, 95.2% (10,984) got IV-zidovudine while 554 did not. A PI-based ART
regimen was the last one prescribed during pregnancy for the majority of women
(60.2%), with 7.2% a non PI-based ART regimen, 2.6% three or more nucleoside
reverse transcriptase inhibitors (NRTIs), 17.5% two NRTIs, 10.2% NRTI
monotherapy and 0.9% an integrase inhibitor or CCR5-based regimen.
The median CD4 count at
delivery was 461 cells/mm3 (IQR: 319-636).
Close to 80% of newborns were given
This analysis shows
IV-zidovudine did not have an effect on MTCT in women with well-controlled
viral load and no apparent childbirth risk factors, but remained effective in
reducing MTCT among women with virological failure at delivery, even among
those on ART during pregnancy.
While the study’s main
strength is the large number of patients, the relative small number (5%) not
getting IV-zidovudine is its main limitation.
Women not getting
IV-zidovudine were more likely to be over 35, to have given birth previously, to have delivered
preterm and vaginally and with high viral load at delivery. The authors
hypothesize this may be because they presented in advanced labour, too late to
Preterm delivery is a risk
factor for MTCT. Vaginal delivery in the absence of ART or with zidovudine
monotherapy alone is linked to higher transmission rates compared to elective
However, there was a
significant five-fold increased risk of MTCT without IV-zidovudine than with
(9.5% compared to 1.8%, p = 0.01) among women with virological failure delivering
at term by elective C-section.
No transmission occurred
among women with viral load under 400 copies/ml (0/369) or even under 1000
copies/ml (0/28) who did not get IV-zidovudine compared to 0.6% (42/7576),
p = 0.17 and 0.9% (5/556), p = 0.61, respectively among those who got
This finding led the authors to
comment that given the large size of the cohort and few
infected infants, the study lacked the power to evaluate the safety of
withholding IV-zidovudine in cases of obstetrical risk factors. They propose,
while awaiting more data, IV-zidovudine be continued in women, even with low
viral load, in cases of complicated deliveries.
These results, consistent
with the authors’ previous findings (1997-2004), allowed the authors to look at
IV-zidovudine with an increased power and within the context of systematic ART
recommended for all pregnant women since 2004. The proportion of those on
PI-based regimens increased from 38% in 1997-2004 to 86% in 2005-2010.
Evaluation of HIV-uninfected
infants in the first six months of life showed IV-zidovudine was not associated
with increased short-term haematological toxicity or lactate levels.