HAART use in pregnant women associated with premature delivery, but not congenital abnormalities

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HIV-infected pregnant women taking highly active antiretroviral therapy (HAART) are more likely to give birth prematurely, according to the results of a 14-year survey presented at the Seventh International Congress on Drug Therapy in HIV Infection last week in Glasgow. The study also found that HAART did not cause a significant increase in congenital abnormalities, although the study only considered HAART as a whole, and did not analyse individual drugs or drug classes separately.

The National Study of HIV in Pregnancy and Childhood (NSHPC) is a voluntary active reporting system of pregnancies in women diagnosed with HIV infection in the United Kingdom and Ireland run under the auspices of the Royal College of Obstetricians and Gynaecologists. It collects data on the timing and type of antiretroviral therapy in pregnancy, pregnancy outcome and demographic details.

“Most diagnosed infected pregnant women take antiretroviral therapy to reduce the risk of vertical transmission, and an increasing number are conceiving on antiretroviral therapy,” state the investigators. “Although this does not appear to be associated with an increased risk of congenital abnormalities, the use of combination antiretroviral therapy is associated with premature delivery.”

Glossary

monotherapy

Taking a drug on its own, rather than in combination with other drugs.

caesarean section

Method of birth where the child is delivered through a cut made in the womb.

vertical transmission

Transmission of an infection from mother-to-baby, during pregnancy, childbirth, or breastfeeding.

 

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

Between 1990 and 2003, there have been 3807 pregnancies in HIV-positive mothers, around 80% of which have resulted in a live or still birth. Two thirds of these deliveries have occurred since 2001.

The study found that use of antiretroviral therapy during pregnancy has increased since 1994, with monotherapy giving way to combination antiretroviral therapy since 1998. Currently, 95% of HIV-positive women take antiretroviral therapy during pregnancy.

Since 2001, 13% of the deliveries have occurred before 37 weeks’ gestation, being 1.47 times more common in mothers taking HAART than those on monotherapy. The elevated rate of prematurity has resulted in around 30% of HIV-positive mothers giving birth vaginally or having emergency caesarean sections, despite having planned to deliver by caesarean section in weeks 38 or 39.

Congenital abnormalities were seen in 100 (3%) of the babies born to HIV-positive mothers. As this rate is similar to that seen in the general population, and the study failed to show any link with time or the use of HAART, the investigators concluded that HAART did not increase the incidence of abnormalities. However, the effect of non-nucleoside reverse transcriptase inhibitors (NNRTIs) or individual drugs, notably efavirenz (Sustiva), cannot be assessed confidently until more data have been gathered by the survey.

The study did find, however, that the incidence of spontaneous abortion has increased over time, with 23% occurring between weeks 20 and 23 of gestation. Although a causative link cannot be proven, Dr Pat Tookey, presenting, speculated that this may be an effect of the increased use of HAART in pregnant mothers.

When comparing mothers taking monotherapy for HIV with those on HAART, use of combination antiretroviral therapy was not associated with an increased risk of stillbirth (monotherapy: 0.5%; HAART: 1.2%; p = 0.1), or neonatal death (0.2 vs. 0.6%, p = 0.2).

References

Tookey P et al. Antiretroviral therapy and pregnancy outcome: UK/Ireland surveillance data 1990-2004. Seventh International Congress on Drug Therapy in HIV Infection, Glasgow, abstract PL11.3, 2004.