Treating HIV-positive pregnant women with a combination of anti-HIV drugs does not increase the chance of premature delivery or still birth, according to a study published in the 13 June edition of the New England Journal of Medicine. The findings contradict earlier studies which found that giving HAART to women with HIV-1 dramatically increased the risk of premature delivery.
Investigators conducted a retrospective analysis of the medical records of 2123 pregnant women with HIV-1 who were enrolled in seven separate clinical trials, received antiretroviral treatment during pregnancy and went on to deliver infants between 1990 and 1998. Of these, 1580 received monotherapy, 396 HAART without a protease inhibitor and 137 HAART with a protease inhibitor. Also included in the study were the records of 1143 pregnant women with HIV-1 who were enrolled in the same studies, but who did not receive any kind of antiretroviral therapy.
Unadjusted rates of premature delivery (before week 37), low birth weight, very low birth weight and still birth did not differ significantly between the treated and untreated groups. However, unadjusted rates for premature delivery were significantly lower in the treatment arm, and were similar for women who received monotherapy or HAART. After adjustment for risk factors such as HIV disease progression, indicated by a low CD4 count, and tobacco, alcohol and illegal drug use, the rates for adverse pregnancy outcomes still remained similar in the treated and untreated groups.
Contrary to the findings of earlier studies, the administration of a protease inhibitor during pregnancy did not lead to increased rates of premature or very premature delivery. Nor were women who received HAART regimens without a protease inhibitor any more likely to have a premature baby.
The study also established that women who were given HAART without a protease inhibitor delivered fewer babies of low or very low birth weight than women who received no therapy or monotherapy. However, women receiving combinations including a protease inhibitor were more likely to have a low or very low birth weight baby than those who either received no therapy at all or monotherapy.
Overall, the study authors found that ‘the risk of an adverse outcome of pregnancy was not associated with the use of combination antiretroviral regimens.’ In particular, ‘the risk of premature delivery was not significantly higher with combination therapy than with monotherapy or no therapy.’
They suggest that their findings contradict earlier studies because the present study was able to adjust for risk factors of adverse outcome in pregnancy, including previous premature delivery, and tobacco, alcohol and illegal drug use. In addition, the investigators were also able to take into account the degree of damage HIV had caused to the mother’s health, a control which was not included in earlier studies.
The authors suggest that women receiving a protease inhibitor may have been at greater risk of delivering a low or very low birth weight baby because of the stage of maternal HIV disease, noting that it was likely that ‘women who received combination therapy with [a] protease inhibitor had more advanced disease.’ However, they argue that the slightly increased risk of having a baby of low birth weight is ‘outweighed by the substantial benefits… [of] protease inhibitors for both mother and infant.’
Limitations of the study include lack of information about the precise time when HAART was initiated, early pregnancy loss, congenital abnormalities, or long-term health of the infants. Nevertheless the study concludes that ‘the risks of adverse outcomes of pregnancy that are attributable to antiretroviral therapy are low and are likely to be outweighed by the recognised benefits of such therapy during pregnancy.’
Tuomala RE et al. Antiretroviral therapy during pregnancy and the risk of an adverse outcome. New England Journal of Medicine 346, 24:1863-1870, 2002.