HIV treatment during pregnancy does not increase the risk of birth abnormalities, according to the results of a large study published in the online version of AIDS. Researchers from the UK and Ireland looked at the outcome of over 8000 pregnancies in HIV-positive women over a 17-year period and found that the rate of birth abnormalities was the same as that seen in the general population.
Furthermore, no individual anti-HIV drug, including efavirenz (Sustiva, also in the combination pill Atripla) was associated with an increased risk of birth abnormalities. Efavirenz is not recommended for use during pregnancy, especially in the first three months, due to findings from animal studies suggesting a risk of birth defects if the developing foetus is exposed to the drug.
HIV treatment dramatically reduces the risk of mother-to-child transmission of HIV. There are concerns, however, that HIV treatment during pregnancy may involve a risk of birth abnormalities (teratogenecity).
Earlier large-scale observational studies have found that there is no increased risk of birth abnormalities if HIV treatment is taken in the first trimester (three months) of pregnancy, the time when the developing foetus is thought most vulnerable to effects of drugs. But there have been reports that treatment with AZT (zidovudine, also in the combination pills Combivir and Trizivir), ddI (didadosine, Videx) and efavirenz involved an increased risk of specific abnormalities.
To help clarify the risk of birth abnormalities associated with HIV treatment during pregnancy, researchers looked at the records of 8242 pregnancies in HIV-positive women in the UK and Ireland between 1990 and 2007.
A total of 232 infants (3%) were born with abnormalities, but a quarter (59) were only minor. When the investigators excluded these the overall rate of birth abnormalities was 2%.
Abnormality rates were lower in babies born to black African mothers (3%) than white mothers (4%). The investigators speculate that this could be because mothers from white backgrounds were more likely to be injecting drug users.
Infants with abnormalities were more likely to be born prematurely and to be boys (3% vs 2% girls). This was due to the higher rate of genital abnormalities, such as undescended testes in boys.
HIV treatment during pregnancy did not increase the risk of birth abnormalities. The rate of such abnormalities in the infants of mothers who did not receive HIV treatment was 3%. It was also 3% in infants whose mothers took HIV treatment during the first three months of pregnancy and 3% in babies whose mothers took anti-HIV drugs later in pregnancy.
The researchers then adjusted their results for potential confounding factors (the ethnicity of the mother, injecting drug use, and health) and found that this did not affect their results: neither the use nor timing of HIV treatment during pregnancy increased the use of birth abnormalities.
Next the researchers looked to see if any class of anti-HIV drug (NRTI, NNRTI or protease inhibitor) was associated with an increased risk of birth abnormalities. Their analysis failed to find any such association.
Possible associations between individual antiretroviral drugs and birth abnormalities were then examined. A total of 205 infants were exposed to efavirenz in the womb, mainly because mothers were already on treatment – or began treatment – before they learnt they were pregnant. Of those exposed during the first trimester, the abnormality rate was 2%. This was no different to the abnormality rate (3%) observed in babies exposed to other antiretroviral drugs early in pregnancy. Reported abnormalities in infants with early exposure to efavirenz included two cases of undescended testes, two cases of dislocated hip and a case of hypertrophic pyloric stenosis (narrowing of the intestines, often associated with severe vomiting).
The rate of abnormalities amongst infants with early exposure to ddI was 3%. The investigators also failed to find any association between the use of AZT during early pregnancy and an increased risk of abnormalities.
When the investigators analysed the type of abnormalities, they found that the most commonly reported were musculoskeletal (40), limb (32), heart/circulatory (30), and genital (22, including nine cases of undescended testes).
None of these types of abnormality was associated with the timing of HIV treatment during pregnancy.
“An overall congenital abnormality rate of 2.8% (2.1% excluding minor defects) was observed in this unselected population of around 8200 infants”, write the investigators. They add, “this is consistent with national populations estimates of 2-3% for major abnormalities in England”.
They emphasise that they failed to find any association between an increased risk of abnormalities and the timing of HIV treatment during pregnancy, nor did they find that any class or individual anti-HIV drug increased the risk of abnormalities.
“These results provide further reassurance that exposure to antiretroviral therapy in utero does not pose a major risk of fetal anomaly”, conclude the investigators.
Townsend CL et al. Antiretroviral therapy and congenital abnormalities in infants born to HIV-infected women in the UK and Ireland, 1990-2007. AIDS 23 (online edition), 2009.