births in HIV-positive women continue to be a concern, and need to anticipated
and managed actively in developing countries, researchers said last week at the
18th Conference on Retroviruses and Opportunistic Infections in Boston.
findings persist over the use of antiretroviral therapy, especially use of
protease inhibitors, during pregnancy and its adverse effects on infants
including pre-term birth. Premature birth and low birth weight increase the
risks for death and disease in both low-resource and high-resource settings.
studies have shown an elevated risk of premature delivery among women who receive
ritonavir-boosted protease inhibitors during pregnancy.
ANRS French Perinatal Cohort French study presented at the conference showed
that women who received a ritonavir-boosted protease inhibitor (PI) were almost
twice as likely to deliver prematurely compared to those getting non-boosted PI
during pregnancy: 14.4% compared to 9.1%; adjusted hazard ratio=2.0(1.1-3.9);
increased risk and mostly induced pre-term delivery could be explained,
perhaps, she noted, by more toxicity in the third trimester.
Maria Isabel González-Tomé, reporting at
the same session on a prospective cohort study from 2000 to 2008 among 803
children born to HIV-positive women in seven Spanish hospitals, found that while
the rate of pre-term birth and low-birth weight was high it was not linked to
any combination of ART regimen. In fact mothers not on ART were at the greatest
risk for pre-term delivery and low-birth weight (RR 2.064, 95% CI: 1.262-3.376;
Thorne of University College, London,
a co-discussant during the poster presentation session, stated that pre-term
delivery is incompletely understood.
that populations selected and methods used are critical to interpretation of
the diverse and often conflicting findings she added “Striking inequalities
exist in survival chances of a preterm infant between developed and developing
countries and possible adverse effects of ART use in pregnancy may be more
difficult to manage in resource-poor settings.”
surprisingly both studies found that older age, intravenous drug use, tobacco
use, no antenatal care/late access to care increased the risks for pre-term
delivery and low birth weight. In the Spanish study hepatitis C co-infection
(RR1.703, 1.31-2.207, p=0.001), low CD4 cell count and high viral load at
delivery also increased the risks.
other presentations in this session reported on these issues in a developing
country with a generalised HIV epidemic, Botswana.
a first report of its kind Natasha Parekh and colleagues looked at the risk
factors including the use of ART for very premature and very-small-for-age
infants born to HIV-positive mothers in six hospitals across Botswana.
16,203 live births from October 2007 to March 2010, 28% (4343) were born to
HIV-positive women of which 4.3% were very pre-term delivery and 3.7% were very
small for gestational age. The associated rates of neonatal deaths were 26% and
pre-term was defined as a birth at under 32 weeks of pregnancy; very small for
age at birth was defined as under 3rd percentile for
high blood pressure, HIV infection and a history of poor obstetric outcomes
that included still birth, pre-term delivery or low birth weight were linked to
both very pre-term delivery and very small for gestational age.
use of antiretrovirals starting before conception was associated with very
small for gestational age (AOR 1.75, 95% CI: 1.21-2.52) and high blood pressure
during pregnancy (AOR 1.34, 95% CI: 1.00-1.77) but not with very pre-term
delivery (AOR: 0.78, 95% CI: 0.49-1.26).
Parekh suggested that control of hypertension in pregnancy may improve
Powis presented data on the effect of protease inhibitor-based ART on pre-term
delivery from the first randomised trial comparing antiretroviral regimens
among pregnant women.
women with CD4 cell counts under or equal to 200 cells/mm3 were
randomised between 26 and 34 weeks of gestation to a PI-based
(lopinavir/ritonavir/zidovudine/lamivudine) or triple nucleoside reverse
transcriptase inhibitor-based regimen (abacavir/zidovudine/lamivudine) in a
clinical trial designed to prevent mother–to-child transmission.
(16.7%) of the 530 women (267 in the PI group and 263 in the NRTI group) who
got ART, for a median of 11.3 weeks before delivery, delivered pre-term. Women
in the PI group were almost twice as likely to deliver pre-term (21.4% compared
to 11.8%, p=0.003);(OR 2.03, 95% CI: 1.26-3.27).
in the PI group gained less weight than those in the NRTI group. However,
weight change was not a significant risk for pre-term delivery.
hospitalisations and infant deaths (12.7% and 14.8% and 1.5% and 1.1%, in the
PI and NRTI groups, respectively) while highest in the first six months of life
did not differ significantly according to maternal ART regimen.
two studies highlight the importance of prioritising high-risk antenatal and
neonatal services in countries like Botswana with generalised HIV
epidemics where ART regimens are used for PMTCT.
as Dr.Powis said “we need to be concerned that PI-based ART carries a higher
risk for pre-term delivery in resource-poor settings and [we] need to be
prepared to deal with it.”
Ekouévi, co-discussant, of the University of Bordeaux, France and of the ANRS
Abidjan, Côte d’Ivoire, concluded that while ART reduces MTCT rate to 1% it
also induces preterm delivery (11%-20%), as a result of which 6% of infants
will die within the first six months.
proposed: “the urgent need to put in place a ‘pregnancy register’ in low-income
countries to better describe
Frequency of pre-term delivery
Relation to type of ART started
Long term follow-up data (death/growth)
Haematological and neuro-development disorders
added that the register should include data from HIV-infected pregnant women as
well as from the general population.