Potent HIV treatment taken during pregnancy that consists of three anti-HIV drugs does not affect the growth of the foetus in the womb, French investigators report in an article published in the online edition of AIDS. The investigators believe that their study shows that modern triple-drug antiretroviral treatment is “not responsible for any type of intrauterine growth retardation”.
The risk of mother-to-child HIV transmission is now very low. This is largely because of HIV treatment. Nevertheless, some studies have shown that taking modern triple-drug HIV treatment during pregnancy, particularly if this includes a protease inhibitor, may increase the risk of having a premature or low birth-weight baby. However, these unwanted outcomes have not been seen in other studies.
Investigators from the ANRS French Perinatal Cohort postulated that the research results showing that the use of modern HIV treatment during pregnancy had adverse outcomes could have been due to methodological reasons.
They therefore undertook their own study to see if HIV treatment during pregnancy affected the growth of infants in the womb. The investigators were careful to ensure that their study took into account any potentially confounding factors. They therefore excluded from their study HIV-infected infants, twins, and the babies of mothers who injected drugs, as these factors can affect the growth of the baby in the womb.
A total of 8192 HIV-negative infants born to HIV-positive mothers between 1990 and 2006 were included in the investigators’ analysis.
The type of HIV treatment recommended for use to prevent mother-to-child HIV transmission changed dramatically over the study period. Between 1994 and 1997, this treatment consisted of AZT monotherapy. This was replaced by dual nucleoside reverse transcriptase inhibitor (NRTI) treatment, which in turn was supplanted by triple drug antiretroviral therapy from 2004.
Between 1994 and 1997, 80% of women received AZT monotherapy during pregnancy. Reflecting the change in treatment guidelines, this fell to 19% between 1999 and 2004 and 2% thereafter. The proportion of women who received triple-drug therapy increased over time, from 14% in 1996 to 1998, to 90% in 2005 to 2006.
The mean birth weight and gestational age at delivery decreased slightly from 3150g and week 39 in 1996 to 3050g and 38 weeks thereafter.
However, the birth-weight adjusted for gestational age increased between 1990 and 1997 and remained stable thereafter.
Furthermore, the proportion of infants assessed as being small for their gestational age remained stable over the entire period of analysis between 4% and 5%.
The researchers did, however, find that there was a non-significant trend for decreased size in infants' head circumference over time (p = 0.07).
Statistical analysis showed that the risk of an infant being born with a small gestational age was not associated with the type of antiretroviral therapy used.
In an attempt to control for confounding factors, the investigators compared the risk of infants being small for their gestational age according to two standards of treatment: AZT monotherapy between 1994 and 1996 and triple-drug antiretroviral therapy between 2005 and 2006. This showed that the risk of an infant being born small for its gestational age was similar for both standards of care.
In further analysis, the investigators found that neither the time triple-drug HIV treatment was commenced during pregnancy, not the duration of such treatment, nor the composition of the treatment combination was associated with an infant being small for its gestational age. Furthermore, height and head-circumference scores were comparable for infants exposed to monotherapy and triple-drug therapy.
“In conclusion”, write the investigators, “our results suggest that the antiretroviral therapies used on a large scale over the past 15 years do not impact on fetal growth”. However, they recommend “these issues should continue to be monitored…because there continue to be changes in guidelines and clinical practice concerning the indications for time to begin and the types of antiretroviral therapies used in pregnant women”.
Briand N et al. No relation between in-utero exposure to HAART and intrauterine growth retardation. AIDS 23 (online edition), 2009.