by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer
April 14, 2020
Chinula L et al. Safety and Efficacy of Dolutegravir versus Efavirenz and Tenofovir Disoproxil Fumarate versus Tenofovir Alafenamide in Pregnancy: IMPAACT 2010 Trial. CROI 2020, Boston, MA. Abstract #130
This study compared the safety and virologic efficacy in pregnancy of three antiviral regimens: Dolutegravir (DTG) + emtricitabine (FTC)/tenofovir alafenamide fumarate (TAF); Dolutegravir + FTC/tenofovir disoproxil fumarate (TDF) and efavirenz (EFV)/FTC/TDF. The trial included 643 HIV-infected women from 22 sites in nine countries. The subjects were randomized (1:1:1) to open-label DTG+FTC/TAF, DTG+FTC/TDF, or EFV/FTC/TDF at 14 to 28 weeks gestational age. The women were allowed to have taken no more than 14 days of antiretroviral therapy (ART) before randomization. The baseline median gestational age at study entry was 22 weeks. Median viral load at baseline was 903 copies/mL and the median CD4 count was 466 cells/µL. The primary goal of IMPACT was comparing the two combined DTG-containing arms to the EFV arm for non-inferiority (- 10% margin), and also superiority, with regards to having a viral load of < 200 copies/mL at time of delivery. Safety outcomes between the three arms included: A) Adverse pregnancy outcomes (preterm delivery <37 weeks, small for GA <10 percentile, spontaneous abortion or stillbirth. B) Maternal grade >3 adverse events through 14 days postpartum; C) infant grade >3 adverse events including neonatal death at <28 days. At time of delivery, 97.5% of women in the combined DTG arms compared to 91% in the EFV arm had viral loads of <200 cp/mL. This difference was statistically significant (p=0.005). Pregnancy outcomes were available for 99.5% of the subjects. Only 24% of women in the DTG+FTC/TAF arm had an adverse pregnancy outcome compared to 33% in the DTG+FTC/TDF and 33% in the EFV/FTC/TDF arms. Two infants were diagnosed with HIV at <14 days, one each in DTG+FTC/TAF and DTG+FTC/TDF arms. For one, the maternal VL at delivery was 58,590 cp/mL however, the second mother was undetectable (< 40 cp/mL), suggesting in-utero transmission occurred.
The findings of the IMPAACT trial should influence clinical practice including an update of the DHHS perinatal guidelines for HIV treatment in pregnancy. Not only were virologic outcomes superior with DTG but there were also fewer adverse events with DTG + FTC/TAF. Data published in 2019 re-established the overall safety and efficacy of DTG use in pregnancy regarding neural tube defects and this update was included in guidance by the World Health Organization. Prior to the IMPAACT trial there was little data on the use of TAF in pregnancy. This study suggests that it may be preferable to TDF.