Table 2.

Active and planned clinical trials of dolutegravir, tenofovir alafenamide, efavirenz 400, in pregnant and breatfeeding women

Trial	Sponsor (collaborators)	Design	Status	Purpose
Dolutegravir
DolPHIN1	University of Liverpool (University of Cape Town, Makerere University)	DTG PK in late presenting (28 to 36 weeks gestation) pregnant women in third trimester and postpartum during 2 weeks breastfeeding; randomised 1:1 to DTG (50 mg once daily) or standard of care (EFV) plus two NRTIs	Started: March 2017	Primary: PK 3rd trimester
			Primary completion: December 2017	Secondary: safety and tolerability of DTG up to 2 weeks post-partum and VL at delivery
PK and safety study in pregnant women with HIV	ViiV Healthcare	Women with unintended pregnancies (estimated n=25) while participating in ARIA study of DTG/ABC/3TC FDC vs ATV/ r +TDF/FTC in 474 treatment naive women	Started: Jan 2015	Primary: PK 2nd/3rd trimester
			Primary completion: February 2019	Secondary: PK in neonate, maternal:cord blood ratio, maternal and infant AEs; adverse pregnancy outcomes
DolPHIN2	University of Liverpool (University of Cape Town, Makerere University, UNITAID)	DTG PK, safety and efficacy in 250 late presenting (≥ 28 weeks gestation) pregnant women in 3rd trimester and post-partum during breastfeeding until weaning or 18 months; randomised 1:1 to receive DTG (50 mg once daily) or standard of care (EFV) plus two NRTIs	Planned start: Q3 2017	Primary: PK 3rd trimester
			Primary completion: Q1 2021	Secondary: viral load at delivery, safety, tolerability breast milk sterilisation
Tenofovir alafenamide
WAVES (OLE)	Gilead Sciences	EVG/COBI/FTC/TDF vs TDF/FTC + ATV/r in treatment naive women with OLE women in ATV/r arm re-randomised to remain or switch to EVG/COBI/FTC/TAF; those that become pregnant can remain on study regimen	Started: February 2016	Safety, efficacy and tolerability in ART naive pregnant women
			Primary completion: March 2017
Dolutegravir and tenofovir alafenamide
VESTED IMPAACT P2010	IMPAACT network NIH (NIAID and NICHD)	DTG/TAF/FTC vs DTG/TDF/FTC vs EFV/TDF/FTC in 549 mother/infant pairs Treatment-naive women starting ART at 14 to 28 weeks gestation	Planned start: March 2017	Comparative data on safety and virologic efficacy during pregnancy and through 50 weeks of maternal and infant follow-up postpartum
			Primary completion: December 2019
IMPAACT P1026s	IMPAACT network NIH (NIAID and NICHD)	PK properties of antiretroviral and related drugs during pregnancy and postpartum; pregnant women > 20 weeks gestation receiving DTG (1 arm) and TAF (3 arms – within FDCs) as part of clinical care	Started: Sep 2014	Primary: PK 2nd /3rd trimester
			Primary completion: June 2017 (DTG) and June 2018 (TAF)	Secondary: PK in neonate, maternal:cord blood ratio, maternal and infant AEs; adverse pregnancy outcomes
PANNA study	Radboud University (PENTA Foundation, ViiV Healthcare)	Pregnant women < 33-week gestation receiving DTG as part of clinical care Each study arm 16 with evaluable 33-week data	Started: July 2015	Primary: PK at 33 weeks and 4–6 weeks after delivery
			Primary completion: Dec 2020	Secondary: PK in neonate, safety, VL and transmission
Efavirenz 400 mg
PK of EFV 400 mg once daily during pregnancy in HIV positive women	SSAT (Mylan Inc.)	PK single arm 25 women stable on 2 NRTI plus EFV 600 mg for >12 weeks, switch to EFV 400 mg at gestational age 28 weeks	Started: Sep 2016	Primary: PK 3rd trimester and postpartum
			Primary completion: May 2017	Secondary: Safety and tolerability, genetic influences on EFV PK

AE, adverse event; ABC, abacavir; ATV/r, atazanavir/ritonavir; COBI, cobicistat; DTG, dolutegravir; EFV, efavirenz; EVG, elvitegravir; FDC, fixed dose combination; FTC, emtricitabine; IMPAACT, International Maternal Pediatric Adolescent AIDS Trials Network; NAID, NIH, United States National Institutes of Health; NRTI, nucleos(t)ide reverse transcriptase inhibitor; OLE, open label extension; PANNA, Study on Pharmacokinetics of Newly Developed ANtiretroviral Agents in HIV-infected pregNAnt Women; PK, pharmacokinetic; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; VL, viral load; 3TC, lamivudine

Adapted from Clayden P. Fit for Purpose. HIV i-Base. February 2017. [77]