DTG + 3TC versus DTG + TDF-FTC as Initial ART
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
DTG + 3TC versus DTG + TDF-FTC as Initial ART
GEMINI 1 and 2: Baseline Characteristics
Source: Cahn P, et al. Lancet. 2019;393:143-55.
• 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)
DTG + 3TC versus DTG + TDF-FTC as Initial ART
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
DTG + 3TC versus DTG + TDF-FTC as Initial ART
GEMINI 1 and 2: Results by Baseline HIV RNA Level
Week 48 Virologic Response (Intention-to-Treat Analysis)
91 91 9293 9490
0
20
40
60
80
100
Pooled Data ≤100,000 >100,000
HIV
RN
A <
50 c
op
ies
/mL
(%
)
Dolutegravir + Lamivudine Dolutegravir + Tenofovir DF-Emtricitabine
Source: Cahn P, et al. Lancet. 2019;393:143-55.
669/717 526/576 531/564 129/140 138/153655/716
Baseline HIV RNA copies/mL
DTG + 3TC versus DTG + TDF-FTC as Initial ART
GEMINI 1 and 2: Results by Baseline CD4 Cell Count
Week 48 Virologic Response (Intention-to-Treat Analysis)
91 93
79
93 93 93
0
20
40
60
80
100
Pooled Data >200 ≤200
HIV
RN
A <
50 c
op
ies
/mL
(%
)
Dolutegravir + Lamivudine Dolutegravir + Tenofovir DF-Emtricitabine
Source: Cahn P, et al. Lancet. 2019;393:143-55.
669/717 605/653 618/662 50/63 51/55655/716
Baseline CD4 Count (cells/mm3)
DTG + 3TC versus DTG + TDF-FTC as Initial ART
GEMINI 1 and 2: Results
Week 48 Changes in Renal Function
Source: Cahn P, et al. Lancet. 2019;393:143-55.
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
Dolutegravir + Lamivudine Dolutegravir + Tenofovir DF-Emtricitabine
DTG + 3TC versus DTG + TDF-FTC as Initial ART
GEMINI 1 and 2: Results
Week 48 Changes in Markers of Renal Proximal Tubulopathy
Source: Cahn P, et al. Lancet. 2019;393:143-55.
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
Dolutegravir + Lamivudine Dolutegravir + Tenofovir DF-Emtricitabine
DTG + 3TC versus DTG + TDF-FTC as Initial ART
GEMINI 1 and 2: Results
Week 48 Changes in Serum Bone Biomarkers
Source: Cahn P, et al. Lancet. 2019;393:143-55.
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)
Dolutegravir + Lamivudine Dolutegravir + Tenofovir DF-Emtricitabine
DTG + 3TC versus DTG + TDF-FTC as Initial ART
GEMINI 1 & 2: Conclusion
Source: Cahn P, et al. Lancet. 2019;393:143-55.
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.”
DTG + 3TC versus DTG + TDF-FTC as Initial ART
GEMINI 1 and 2: Results by Baseline HIV RNA Level
Week 96 Virologic Response (Intention-to-Treat Analysis)
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
(%
)
Dolutegravir + Lamivudine Dolutegravir + Tenofovir DF-Emtricitabine
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
DTG + 3TC versus DTG + TDF-FTC as Initial ART
GEMINI 1 and 2: Results by Baseline CD4 Cell Count
Week 96 Virologic Response (Intention-to-Treat Analysis)
86 88
68
90 90 87
0
20
40
60
80
100
Pooled Data >200 ≤200
HIV
RN
A <
50 c
op
ies
/mL
(%
)
Dolutegravir + Lamivudine Dolutegravir + Tenofovir DF-Emtricitabine
Source: Cahn P, et al. J Acquir Immune Defic Syndrome. 2019 Dec 10. Epub ahead of print
642/717 573/653 594/662 43/63 48/55616/716
Baseline CD4 Count (cells/mm3)
DTG + 3TC versus DTG + TDF-FTC as Initial ART
GEMINI 1 and 2: Results
Week 96 Changes in Renal Function
Source: Cahn P, et al. J Acquir Immune Defic Syndrome. 2019 Dec 10. Epub ahead of print
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
Dolutegravir + Lamivudine Dolutegravir + Tenofovir DF-Emtricitabine
DTG + 3TC versus DTG + TDF-FTC as Initial ART
GEMINI 1 and 2: Results
Week 96 Changes in Serum Bone Biomarkers
Source: Cahn P, et al. J Acquir Immune Defic Syndrome. 2019 Dec 10. Epub ahead of print
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)
Dolutegravir + Lamivudine Dolutegravir + Tenofovir DF-Emtricitabine
DTG + 3TC versus DTG + TDF-FTC as Initial ART
GEMINI 1 and 2: Week 96 Conclusion
Source: Cahn P, et al. J Acquir Immune Defic Syndrome. 2019 Dec 10. Epub ahead of print
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.