DTG + 3TC versus DTG + TDF-FTC as Initial ART GEMINI 1 and ...

DTG + 3TC versus DTG + TDF-FTC as Initial ART

GEMINI 1 and GEMINI 2: Week 48 Data


GEMINI 1 and 2: Background

Source: Cahn P, et al. Lancet. 2019;393:143-55.

Study Design: GEMINI 1 and 2

• Background:

- Two identical, double-blind, multinational,

noninferiority, randomized controlled trials

that compared initial antiretroviral therapy

(ART) of dolutegravir plus lamivudine (DTG +

3TC) versus dolutegravir plus tenofovir-DF-

emtricitabine (DTG + TDF-FTC)

• Enrollment Criteria:

- Treatment-naïve adults

- HIV RNA 1,000-500,000 copies/mL

- No NRTI, INSTI, or major PI mutations

- No chronic HBV

- No need for HCV therapy

- Not pregnant or breastfeeding

DTG + 3TC

(Dual ART)n = 716

DTG + TDF-FTC

(Triple ART)n = 717

Primary endpoint: % with HIV RNA

<50 copies/mL at 48 weeks by ITT


GEMINI 1 and 2: Baseline Characteristics


• Source: Cahn P et al. Lancet. 2019;393(10167):143-155GEMINI 1 and 2 Baseline Characteristics

CharacteristicDTG + 3TC

(n = 716)

DTG + TDF-FTC(n = 717)

Age, years, median (IQR) 32 (26-40) 33 (26-42)

Female, n (%) 113 (16) 98 (14)

White, n (%) 480 (67) 497 (69)

Black or African American, n (%) 99 (14) 76 (11)

CD4 cell count, mean (SD) 462 (219.2) 461.3 (213.1)

CD4 count ≤200 cells/mm3, n (%) 63 (9) 55 (8)

HIV RNA (log10 copies/mL) 4.42 (0.66) 4.45 (0.65)

≤100,000 copies/mL, n (%) 576 (80) 564(79)

>100,000 copies/mL, n (%) 140 (20) 153 (21)


GEMINI 1 and 2: Results

Week 48 Virologic Response (Intention-to-Treat Analysis)

91 909393 93 94

0

20

40

60

80

100

Pooled Data GEMINI-1 GEMINI-2

HIV

RN

A <

50 c

op

ies

/mL

(%

)

Dolutegravir + Lamivudine Dolutegravir + Tenofovir DF-Emtricitabine

Source: Cahn P, et al. Lancet. 2019;393:143-55

669/717 320/356 332/358 335/360 337/359655/716


GEMINI 1 and 2: Results by Baseline HIV RNA Level


91 91 9293 9490

0

20

40

60

80

100

Pooled Data ≤100,000 >100,000

HIV

RN

A <

50 c

op

ies

/mL

(%

)



669/717 526/576 531/564 129/140 138/153655/716

Baseline HIV RNA copies/mL


GEMINI 1 and 2: Results by Baseline CD4 Cell Count


91 93

79

93 93 93

0

20

40

60

80

100

Pooled Data >200 ≤200

HIV

RN

A <

50 c

op

ies

/mL

(%

)



669/717 605/653 618/662 50/63 51/55655/716

Baseline CD4 Count (cells/mm3)



Week 48 Changes in Renal Function


10.4

-12.1

-0.1

6.3

13.5

-15.5

0

4.1

-20

-15

-10

-5

0

5

10

15

20

Creatinineμmol/L

GFR by creatinine(mL/min/1.73 m2)

Cystatin C(mg/L)

GFR by cystatin CCKD-EPI (mL/min per

1.73 m2)

Ad

juste

d M

ed

ian

Ch

an

ge f

rom

Baseli

ne




Week 48 Changes in Markers of Renal Proximal Tubulopathy


0.870.93 0.92

1.031.11

1.31

0.0

0.5

1.0

1.5

2.0

Protein to creatinine (g/moL) Retinol-binding protein creatinine (μg/mmoL)

β-2 microglobulin creatinine (μg/mmoL)

Rati

o o

f W

eek 4

8 t

o B

aselin

e




Week 48 Changes in Serum Bone Biomarkers


1.220.60 0.40 0.14

4.07

6.17

13.10

0.330.0

2.5

5.0

7.5

10.0

12.5

15.0

Bone-specific alkalinephosphatase

Osteocalcin Procollagen 1 N-terminal propeptide

Type 1 collagen C-telopeptide

Ad

juste

d M

ean

Ch

an

ge f

rom

B

aselin

e (μg

/L)



GEMINI 1 & 2: Conclusion


Interpretation: “The non-inferior efficacy and similar tolerability profile of

dolutegravir plus lamivudine to a guideline-recommended three-drug

regimen at 48 weeks in ART-naive adults supports its use as initial

therapy for patients with HIV-1 infection.”


GEMINI 1 and GEMINI 2: Week 96 Data


GEMINI 1 and 2: Results by Baseline HIV RNA Level


86 87 8490 90

86

0

20

40

60

80

100

Pooled Data ≤100,000 >100,000

HIV

RN

A <

50 c

op

ies

/mL

(%

)


Source: Cahn P, et al. J Acquir Immune Defic Syndrome. 2019 Dec 10. Epub ahead of print

499/576 510/564 117/140 132/153

Baseline HIV RNA copies/mL

642/717616/716


GEMINI 1 and 2: Results by Baseline CD4 Cell Count


86 88

68

90 90 87

0

20

40

60

80

100

Pooled Data >200 ≤200

HIV

RN

A <

50 c

op

ies

/mL

(%

)



642/717 573/653 594/662 43/63 48/55616/716

Baseline CD4 Count (cells/mm3)



Week 96 Changes in Renal Function


12.3

-14.6

10.7

15.4

-18.2

8.8

-25

-20

-15

-10

-5

0

5

10

15

20

25

Creatinine(μmol/L)

GFR from creatinine, CKD-EPI(mL/min/1.73 m2)

GFR from cystatin CCKD-EPI (mL/min per 1.73 m2)

Ad

juste

d M

ed

ian

Ch

an

ge f

rom

Baseli

ne




Week 96 Changes in Serum Bone Biomarkers


0.29 0.27

11.00

0.10

2.364.21

23.70

0.240

5

10

15

20

25

30

Bone-specific alkalinephosphatase

Osteocalcin Procollagen 1 N-terminal propeptide

Type 1 collagen C-telopeptide

Ad

juste

d M

ean

Ch

an

ge f

rom

B

aselin

e (μg

/L)



GEMINI 1 and 2: Week 96 Conclusion


Conclusion: “Consistent with 48-week data, dolutegravir + lamivudine

demonstrated long-term, non-inferior efficacy vs dolutegravir + tenofovir

disoproxil fumarate/emtricitabine without increased risk of treatment

emergent resistance, supporting its use in treatment-naive HIV-1–

infected individuals.”

Acknowledgment

The National HIV Curriculum is an AIDS Education and Training Center

(AETC) Program supported by the Health Resources and Services

Administration (HRSA) of the U.S. Department of Health and Human

Services (HHS) as part of an award totaling $800,000 with 0% financed

with non-governmental sources. This project is led by the University of

Washington’s Infectious Diseases Education and Assessment (IDEA)

Program.

The content in this presentation are those of the author(s) and do not necessarily represent

the official views of, nor an endorsement, by HRSA, HHS, or the U.S. Government.

DTG + 3TC versus DTG + TDF-FTC as Initial ART GEMINI 1 and ...

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