Use of tenofovir during pregnancy does not
have an adverse impact on infant weight or size at birth, according to a large
US study published in the online edition of AIDS.
The study involved the HIV-negative infants of HIV-positive mothers.
However, its results showed that maternal
use of tenofovir during pregnancy was associated with a reduction in some
parameters of infant growth at one year of age, a finding which the
investigators found “unexpected”.
“The overall findings of this extensive
analysis, however, are highly reassuring,” comment the authors.
Tenofovir (Viread, also in the combination pills Truvada, Atripla and Eviplera) is a
potent antiretroviral drug which is widely used in first-line HIV therapy.
Guidelines in the US, UK and other countries support its use during pregnancy.
However, data on the drug’s impact on
infant growth are largely lacking. A chart review of 14 infants whose mothers
used tenofovir during pregnancy identified a single baby which was small for
gestational age. One experimental study conducted in Rhesus macaques showed
that administration of high tenofovir doses during the first trimester was
associated with lower birth weight and length.
Given this lack of data, investigators from
the US Pediatric HIV/AIDS Cohort Study network investigated the relationship
between treatment with tenofovir during pregnancy and infant size at birth and
infant growth at one year of age.
Parameters of infant weight and size
assessed at birth included:
Measures of infant growth assessed at one
year of age included:
A total of 2029 HIV-negative infants of
HIV-positive mothers were included in the study. A total of 449 infants (21%)
were exposed to tenofovir. Use of the drug during pregnancy increased from 14%
in 2003 to 43% in 2010. “The increasing use of tenofovir by HIV-infected
pregnant women warrants careful evaluation of the safety of this agent,” write
Tenofovir was used by 13% of mothers during
the first trimester of pregnancy.
A low birth weight was observed in 19% of
infants and a very low birth weight in 3%. A total of 9% of infants were small
for their gestational age.
However, there was no difference in the
prevalence of infants with a low birth weight according to the use of tenofovir
during pregnancy. Nor was there any significant difference in the size for
gestational age for the infants of mothers who took tenofovir during pregnancy
and those who did not.
By one year of age, the infants were close
to US growth standard. Mean weight-for-age z score (or standard score) was 0.06 below the average,
mean length-for-age z score was 0.03
below the average, and mean head circumference-for-age z score was 0.34 above
Despite this, there were slight but
significantly lower mean length-for-age z scores and head circumference-for-age
adjusted z scores for infants exposed to tenofovir in utero, compared to those exposed to alternative antiretrovirals
(p = 0.04 and p = 0.02 respectively).
“The magnitudes of these differences were
quite small,” note the investigators, who add that their findings are of
“uncertain significance”. The authors believe their study suggests that
tenofovir use during pregnancy does not affect foetal growth, but could affect
the development of infants during the first year, after exposure to tenofovir
“Several studies of ARV-exposed infants
born to HIV-infected mothers demonstrate the potential for late adverse effects
that may be attributable to perinatal ARV exposure,” write the authors.
However, they note that this occurred after the use of more toxic anti-HIV
drugs, including agents now known to cause mitochondrial toxicity.
“On the whole, these data provide
reassurance about the lack of major detrimental effects on fetal and infant
growth when tenofovir is used in combination ARV regimens in pregnancy,”
conclude the investigators. “The unexpected observation of lower mean length
and head circumference at one year of age warrants further studies monitoring
long-term growth outcomes of tenofovir exposed infants."