Table 2:

Summary of in vivo reproductive studies with DTG

Animal model, study	Regimen	Dosage (mg/kg)	Treatment start	N (Litters)	Results
C57BL/6J female mice⁴⁰	1xDTG (DTG/FTC/TDF) equivalent to human therapeutic drug levels	2·5/33·3/50	GD 0.5	150	Five cases of NTDs were observed in the therapeutic 1xDTG dosage only. Two had exencephaly, two had spina bifida, and one had potential anencephaly.
	5xDTG (DTG/FTC/TDF) reaching supratherapeutic levels	12·5/33·3/50	GD 0.5	111
	Control, water	-		91
C3H/HeJ female mice⁴¹	DTG	50	GD 0·5	17	Exencephaly in one fetus in DTG arm but N insufficient for statistical power.
C3H/HeJ female mice⁴¹	Control, vehicle	-	GD 0·5	9
Sprague-Dawley female rats³⁹	DTG	5	GD 6	22	No significant differences in external abnormalities. Meningocele/absent eye bulge at 1000mg/kg dose but N insufficient for statistical power.
	DTG	50		21
	DTG	100		27
	DTG	300		27
	DTG	1000		47
	Control	-		49
Japanese white female rabbits³⁹	DTG	40	GD 6	19	No significant differences in external abnormalities observed. One cranioschisis at 40mg/kg dose but N insufficient for statistical power.
	DTG	100		3
	DTG	200		18
	DTG	300		5
	DTG	1000		24
	Control	-		24

Abbreviations: DTG, dolutegravir; FTC, emtricitabine; GD, gestational day; TDF, tenofovir disoproxil fumarate.