2019 Ryan White HIV/AIDS Program CLINICAL CONFERENCE

DTG vs EFV When Starting ART in Late Pregnancy Khoo Set al. CROI2019 Seattle,WAAbs.40LB

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 Open-label randomized trial of DTG+2NRTI vs EFV+2NRTI in 268 pregnant ART-naïve women presenting to antenatal clinic at ≥28- 36 weeks gestation in Kampala and Cape Town.

 Primary endpoint is virologic response (VL <50) at delivery.

Start EFV ART Randomizemedian 3d

delivery

2wk PP

6wk PP

48wk PP

24wk PP

12wk PP

72wk PP

4wk

MaternalVLall

ART- naïve >28-36 wks gest

EFV + 2 NRTI

EFV + 2 NRTI

InfantVL (dx)

DTG+ 2 NRTI

DTG + 2 NRTI

‒ Analysis at delivery (ITT): 122DTG,115EFV ‒ Median gestation age at enrollment, 31weeks ‒ No difference in baseline VL (median 4.4 log), CD4 (median 445),prior obstetric history,gestation, BMI

Slide25of42FromJRAnderson,MDatNewOrleans,LA,December4-7,2019,RyanWhiteHIV/AIDSProgramCLINICALCONFERENCE, IAS  USA.

More Rapid VL Decline with Dolutegravir than Efavirenz Khoo Set al. CROI2019 Seattle,WAAbs40LB

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

Primary outcome – Time on medicationbefore delivery, median 55 days

Delivery

Dolutegravir

Efavirenz

aRR DTG vs EFV* P value

VL <50

73.8% (90/122)

42.6% (49/115)

1.66 (1.2, 2.1)

<0.0001

VL <1000

92.6% (113/122)

82.6% (95/115)

1.11 (1.0, 1.2)

0.0513

*Adjusted for age, country, VL (<> 100,000), CD4 (<>200), GAat start ART

100%

DTG EFV

78.9%

Lowerefficacy bothathighRNA

75.9%

74.5%

80%

73.7%

70.8%

57.1%

60%

48.9%

45.9%

44.4%

44.1%

42.6%

40%

30.8%

23.5%

14.3%

20%

Percent VL<50 c/mL

0%

Overall

VL<100,000 VL>=100,000 CD4>=200 CD4<200 GA<36wk GA>=36wk

TotalN

237 198 39 206 31 200

37

VLstrata

CD4strata

GAatentry strata

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Pharmacokinetics in Pregnancy

• EVG/COBI: lower drug levels in 3 rd trimester (P1026); only 74% of women maintained viral suppression at delivery • DRV/COBI: low drug levels in late pregnancy and high rates of virologic failure in late pregnancy; once daily dosing of DRV not recommended in pregnancy • ATV/COBI: PK data not yet available, but anticipated to be similar to DRV/COBI • LPV/r : dose adjustment recommended in 2/3 trimester • ATV/r: consider dose adjustment in 2/3 trimester

Slide27of42FromJRAnderson,MDatNewOrleans,LA,December4-7,2019,RyanWhiteHIV/AIDSProgramCLINICALCONFERENCE, IAS  USA.