Résumé
Introduction: First-line treatment with dolutegravir (DTG) leads to rapid suppression of HIV RNA, which might then lower the risk of mother-to-child HIV transmission (MTCT). Worldwide, millions of women are taking DTG, so safety in pregnancy requires careful evaluation in randomised trials. Clinical obesity is associated with a wide range of adverse birth outcomes.Methods: Data on adverse birth outcomes was included from five randomised trials: DolPHIN-1, DolPHIN-2, ADVANCE, NAMSAL and IMPAACT-2010. These trials compared DTG with efavirenz (EFV) as first-line treatment. In each trial, data on adverse events, adverse birth outcomes and MTCT were collected prospectively. Meta-analysis was conducted using RevMan Software (version 5.3). The odds ratio (OR) for endpoints were calculated using the CochraneMantel-Haenszel test (random-effects model).Results: DolPHIN-1 and DolPHIN-2 were conducted in South Africa and Uganda, ADVANCE in South Africa, NAMSAL in Cameroon and IMPAACT-2010 internationally. DolPHIN-1, DolPHIN-2 and IMPAACT-2010 were conducted in women already pregnant at screening. ADVANCE and NAMSAL were conducted in women who were not already pregnant at baseline. In the meta-analysis, there were 26/657 stillbirths for DTG-treated mothers versus 9/417 for EFV-treated mothers (OR 1.77, p = 0.17) (Figure 1). There were five cases of MTCT for DTG arms and one for EFV (OR 2.80, p = 0.27). There were 14 neonatal deaths for DTG versus 13 for EFV (OR 0.91, p = 0.93). On combining the sum of stillbirths, MTCT and neonatal deaths there were 45 events for DTG versus 24 for EFV (OR 1.20, p = 0.49). No cases of neural tube defects (NTDs) were observed among infants born in any of the trials. In the ADVANCE trial, the risk of developing clinical obesity (BMI >30 kg/m2 ) was significantly higher for women taking DTG/FTC/TAF for 4 years (42%) versus DTG/FTC/TDF (27%) or EFV/FTC/TAF (20%).Conclusions: In this analysis of 1074 pregnant women, there was no significant difference between DTG and EFV in the overall risk of neonatal deaths, stillbirths or MTCT cases. This analysis includes outcomes after first-line treatment, typically up to 6 months before birth. Outcomes for women becoming pregnant after long-term treatment could be different, given higher risks of clinical obesity for DTG, especially if combined with TAF/FTC.