Dolutegravir in pregnancy: early data reassuring but ongoing surveillance is still essential

A recent systematic review of dolutegravir (DTG) in HIV positive pregnant women did not show evidence for increased risks of stillbirth, preterm birth, small for gestational age or congenital anomalies, compared to historical control studies of antiretroviral-treated pregnant women.

Although these results are reassuring, the authors of the review, published in the Journal of Virus Eradication, April 2018, stress that continued pharmacovigilance is essential as up to 15 million people could be receiving antiretroviral treatment with DTG over the next five years and among these a substantial proportion will be women of child-bearing potential.

In many countries with large HIV epidemics, unplanned pregnancies are common and access to both contraceptive services and antenatal clinic facilities may be limited.

The authors included six databases in this analysis, with a total of 1200 pregnant women. The percentage of pregnant women taking DTG with adverse birth outcomes and congenital abnormalities was similar to results from historical control studies of HIV positive women.

But, there was significant heterogeneity across the six databases: percentage of infants with congenital anomalies ranged from 0.0% in Botswana (0/116 infants) to 13.3% in IMPAACT P1026s (2/15 infants).

The authors also noted that there are insufficient data yet recorded for mothers treated with DTG pre-conception.

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None of the studies included in this analysis was a randomised clinical trial comparing outcomes for women taking DTG compared with other antiretrovirals in pregnancy.

A number of randomised trials of DTG have been conducted over the past five years, but (as usual) pregnant women have been excluded.

There are also no robust systems in place to collect and review observational data broadly across countries and settings.

Several investigator-led studies now are underway but results will not be available until 2019–2020.

It is hard to think of new ways to say that pregnant women should be included earlier in clinical trials of investigational drugs. Currently decisions about the safety and efficacy of new antiretrovirals in pregnancy are informed by non-randomised studies and observational cohorts, which could be prone to bias.

Currently, the rapid introduction of DTG in low-and middle-income countries is informed by insufficient data for women who could become pregnant.