No increased adverse outcomes among women starting dolutegravir before conception in the ADVANCE study

Women who started dolutegravir (DTG)-based ART before conception did not have higher rates of adverse pregnancy outcomes compared with those starting efavirenz (EFV) in a South African study comparing three first-line regimens – according to data presented at 13th INTEREST workshop.

The ongoing, 96-week, phase 3, randomised ADVANCE study (n=1053) is evaluating the safety and efficacy of DTG + tenofovir alafenamide (TAF) + emtricitabine (FTC) vs DTG + tenofovir disoproxil fumarate (TDF) + FTC vs EFV + TDF + FTC.

The pregnancy sub study included all women who completed week 48, receiving ART before conception, had gestational age assessment (early ultrasound) and congenital foetal anomaly screening.

Women in the DTG arms were switched to alternative  regimens if pregnancy was less than 8 weeks’ gestation.

Adverse outcomes included: spontaneous abortion, elective termination, preterm delivery, small for gestational age, still birth and neonatal death. The sub study also evaluated neonate HIV status and birth defects.

There were 78 pregnancies among 625 women participating in ADVANCE (12.5%). Of these 15 (19.2%) were spontaneous abortion, 19 (24.4%) elective abortion, 1 (1.3%) stillbirth, 1 (1.3%) neonatal death, 34 (43.6%) live births and 8 (10.3%) pregnancies were ongoing at the time of analysis.

Approximately two thirds of pregnancies were among women in the DTG arms: 29 DTG + TAF + FTC and 21 in DTG + TDF + FTC.

Median birth weight was similar across treatment arms: 3.1 kg (IQR 2.9 to 3.3). A slightly higher proportion of infants exposed to EFV + TDF + FTC were small for gestational age: 22.2% vs 12.5% with DTG + TAF + FTC and  16.7% with DTG + TDF + FTC arms, p=0.768. All subgroup comparisons for all adverse pregnancy outcomes were p >0.10.

There were no vertical transmissions in this sub study. Two infants in the DTG arms had minor birth defects: naevus flammeus and  umbilical hernia.

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Presenting author Dr Chandiwana reminded us of the importance of pooling data across similar trials and of prospective birth surveillance studies in African countries.

She noted that these data will also be submitted to the Antiretroviral Pregnancy Registry.

ChandiwanaN et al. Pregnancy and infant outcomes among HIV positive women on dolutegravir versus efavirenz-based antiretroviral therapy: week 48 analysis of the ADVANCE trial. 13th INTEREST. Accra, Ghana. 14–17 May 2019. Mini oral abstract 15.