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:
Small for gestational age.
Low birth weight (below 2.5 kg) and very low birth weight (below 1.5 kg).
Measures of infant growth assessed at one year of age included:
Weight-for-age z score.
Length-for-age z score.
Head circumference-for-age z score.
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 the investigators.
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 that expected.
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 has ceased.
“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."
Siberry GK et al. Safety of tenofovir use during pregnancy: early growth outcomes in HIV-exposed uninfected infants. AIDS 26, online edition. DOI: 10.1097/QAD.0b013e328352d135, 2012 (click here for the free abstract).