African study looks at safety of antiretroviral therapy during pregnancy

Combination antiretroviral therapy significantly reduces the risks of women with advanced HIV disease having an HIV-infected baby, but increases the risk of having a low birth weight baby, according to research conducted in Ivory Coast and published in the September 12^th edition of AIDS.

But the investigators found that low birth weight did not increase the risk of infant mortality – the only risk factor for this outcome was HIV infection in the infant.

There has been a lot of debate about the safety of triple-drug combination HIV treatment during pregnancy. Although it has been consistently shown to prevent mother-to-child transmission of HIV, studies conducted in rich countries like the UK, Europe and the US, have produced conflicting results about the risks of premature delivery or having a baby with a low birth weight.

So far there has been limited experience of using triple-drug combination antiretroviral therapy during pregnancy in Africa and there is therefore very little information about the effect of such therapy on pregnancy outcomes.

Therefore an international team of investigators analysed results from two cohorts of HIV-positive pregnant women in Ivory Coast. These women received different types of antiretroviral treatment to prevent mother-to-child transmission of HIV.

The first group of women, who were studied between 2001 and 2003, were provided with a short course of either AZT, or AZT plus 3TC, with a single dose of nevirapine during labour. The second cohort involved women who received triple-drug antiretroviral therapy between late 2003 and 2007.

As prophylaxis against HIV infection, the infants of women in both cohorts received two doses of nevirapine and AZT syrup for seven days after birth. In addition, both groups of women were counselled to either formula feed or exclusively breastfeed.

The investigators compared rates of still birth, low birth weight (below 2500g), very low birth weight (below 2000g) and infant mortality (infant death within one year) between the two cohorts of women.

Median CD4 cell count in the 175 women in the first group who received short-course monotherapy or dual therapy was 177 cells/mm³, and the median CD4 cell count amongst women treated with triple drug therapy was 182 cells/mm³, a non-significant difference. The median duration of short-course monotherapy or dual therapy was a little under five weeks, the median duration of triple drug treatment was almost twelve weeks.

First the investigators looked at the rate of stillbirths in the two cohorts. They found that this did not differ significantly at approximately 3% for both groups.

Next they analysed data on the number of low birth weight infants. This showed that 22% of the babies of mothers treated with triple-drug therapy had a low birth weight compared to 12% of the infants of mothers who received single or dual drug therapy, a statistically significant difference (p = 0.02).

When the investigators restricted their analysis to women treated with triple-drug therapy, they found there was no difference in the risk of having a low birth weight baby between women who started triple drug treatment before pregnancy (25%) and those who started such treatment during pregnancy (21%).

In addition to the use of triple-drug treatment (p = 0.03), a low maternal body mass index (below 25kg/m², p = 0.013), was associated with the risk of having a low birth weight baby.

There was no difference between the two cohorts of women in the risk of having a very low birth weight baby.

A total of 16% of the babies born to mothers who received monotherapy or dual HIV therapy had an HIV-infected baby compared to 2% of the mothers who received triple drug antiretroviral treatment.

Approximately 7% of infants died in the first year of life. But neither low birth weight, nor maternal use of triple-drug therapy were risk factors for infant mortality. The only risk factor for this outcome was paediatric HIV infection (adjusted odds ratio, 11.9, 95% CI, 4.8 – 29.5).

The investigators conclude that “further large scale international pharmaco-vigilance systems should be established to assess pregnancy outcomes in the context of this wider use of antiretroviral therapy in pregnant women.”