HIV-positive women who are already taking antiretroviral therapy when they become pregnant are more likely to have a premature or low birth-weight baby than women who initiate HIV treatment after the first three months of pregnancy, Brazilian researchers report in the April edition of Sexually Transmitted Infections.
Over the last decade, standard treatment to prevent mother-to-child transmission of HIV has changed in high and middle-income nations from consisting of AZT monotherapy to triple-drug antiretroviral therapy. The risk of vertical HIV transmission when such treatment is used is very low.
Studies examining the risks to the baby of HIV treatment during pregnancy have yielded conflicting results. Research conducted in Europe has found that antiretroviral therapy, particularly with a protease inhibitor, increases the risk of having a premature delivery. The same research found that HIV treatment was associated with an increased risk of having a low birth-weight baby. By contrast, most studies examining this issue in the US and Latin America have failed to find any such associations.
European researchers also found that women who initiated HIV treatment before conception were significantly more likely to have a premature delivery than women who started antiretroviral therapy after the first three months of pregnancy.
To gain a better understanding of the risks associated with HIV treatment and having a premature or low birth-weight baby, investigators in Rio de Janeiro conducted a prospective, single-site study involving 696 pregnancies in HIV-positive women between 1996 and 2006. The women were stratified according to whether they started HIV treatment before conception or after the first three months of their pregnancy.
Premature delivery was defined as delivery before week 37 of pregnancy, and a baby was defined as having a low birth weight if it weighed below 2.5kg at birth.
Before 1998, HIV treatment in Brazil consisted of dual-drug therapy. After this date, triple-drug antiretroviral treatment became freely available.
A total of 130 women (19%) conceived when already taking HIV treatment. Just under a quarter (23%) were taking dual-drug NRTI treatment, 36% a combination that included a non-nucleoside reverse transcriptase inhibitor (NNRTI) and 41% a protease inhibitor. Viral load was undetectable in 47% of these women at the time of delivery.
Antiretroviral treatment was started after the first three months of pregnancy by 566 women. AZT monotherapy was taken by 32%, dual NRTI treatment by 32% and triple-drug therapy by 36%. Of the 205 women who took triple-drug therapy, 140 received a protease inhibitor and 65 an NNRTI-based treatment.
Most (70%) of the babies were delivered by caesarean section. There was no difference in mode of delivery between the two treatment groups. The median duration of pregnancy at the time of delivery was 38.5 weeks.
There were seven (1%) cases of mother-to-child HIV transmission. Only one of these involved a mother who was already taking antiretroviral drugs at the time of conception.
Overall, 80 (12%) of infants were delivered prematurely and 90 (13%) had a low birth weight.
The investigators’ first set of statistical analysis showed that both these outcomes were associated with a maternal viral load above 10,000 copies/ml at the time of delivery and the use of antiretroviral drugs before conception. High blood pressure was also significantly associated with these adverse outcomes.
In multivariate analysis, the investigators found a significant association between the use of triple-drug antiretroviral therapy before conception and premature delivery (adjusted odds ratio [AOR] 5.06; 95% CI 1.5-17.0) and a viral load above 10,000 copies/ml at the time of delivery (AOR 5.5, 95% CI 1.0-30.8). Use of triple combination therapy before conception was also associated with having a baby with a low birth weight (AOR 3.6; 95% CI 1.7-7.7), as was high blood pressure (AOR 3.8; 95% CI 2.24-8.26).
“Highly active antiretroviral therapy use pre-conception is associated with a 3.6-fold increased risk of low birth weight and a fivefold increased risk of premature delivery”, comment the investigators.
They conclude, “as the number of patients who become pregnant while on antiretrovirals is increasing worldwide, detecting risk factors for adverse outcomes early in gestation will clearly be important to improve the management of such women”.
Machado ES et al. Pregnancy outcome in women infected with HIV-1 receiving combination antiretroviral therapy before versus after conception. Sex Transm Infect 85: 82-87, 2009.