Dolutegravir-Lamivudine (Dovato)
Prepared by:
Brian R. Wood, MDDavid H. Spach, MD
Last Updated: December 22, 2019
Dolutegravir-Lamivudine (Dovato)
Photograph courtesy of ViiV
INSTI NRTI
50 mg 300 mg
Dose: 1 tablet once daily with or without food
Dovato[doe VAH toe]
Dolutegravir-Lamivudine
Dolutegravir-Lamivudine (Dovato)
• Class
- Dolutegravir: integrase strand transfer inhibitor (INSTI)
- Lamivudine: nucleoside reverse transcriptase inhibitor (NNRTI)
• Indication
- Initial therapy for adults with no antiretroviral treatment history and
with no known or suspected substitutions associated with resistance to
dolutegravir or lamivudine
• Dose
- Fixed dose tablet: Dolutegravir 50 mg and Lamivudine 300 mg
- 1 tablet once daily with or without food
• Adverse Events
- Headache, diarrhea, nausea, insomnia, and fatigue
- Possible neural tube defects with dolutegravir
• Initial 2-Drug Therapy
- GEMINI 1 and 2: DTG + 3TC versus DTG + 2 NRTI’s
- PADDLE: Dolutegravir-lamivudine single arm
- ACTG 5353: Dolutegravir-lamivudine single arm
• Maintenance 2-Drug Therapy
- LAMIDOL: Dolutegravir-lamivudine single arm
- ASPIRE: Dolutegravir-lamivudine vs. continued 3-drug ART
- TANGO*: DTG + 3TC vs. TAF-based 3-drug ART
*Results unpublished
Dolutegravir-Lamivudine
Summary of Key Studies
Dolutegravir-Lamivudine
INITIAL THERAPY
DTG + 3TC versus DTG + TDF-FTC as Initial ART
GEMINI 1 and GEMINI 2: Week 48 Data
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 GEMINI 2: Week 96 Data
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.”
Dolutegravir + Lamivudine as Initial Dual Therapy
PADDLE
Dolutegravir plus Lamivudine as Initial Dual Therapy
PADDLE: Design
Source: Cahn P, et al. J Int AIDS Soc. 2017;20:1-7.
Study Design: PADDLE
• Background: Pilot, phase 4, single-arm,
open-label trial conducted in Argentina to
evaluate the efficacy and tolerance of once
daily dolutegravir plus lamivudine as initial
dual therapy
• Inclusion Criteria (n = 20)
- Age ≥18 years
- Antiretroviral therapy naive
- Nadir CD4 count >200 cells/mm3
- HIV RNA >5,000 and ≤100,000 copies/mL
- Wild-type baseline genotype
- No HBV co-infection
• Regimen (Once daily)
- Dolutegravir 50 mg + Lamivudine 300 mg
Dolutegravir
+ Lamivudine(n = 10)
*Cohort 1 *Cohort 2
Cohort 2 patients enrolled following confirmation
that 8/10 patients had >1 log decrease in HIV
RNA at week 8
Dolutegravir
+ Lamivudine(n = 10)
4 patients enrolled with HIV RNA >100,000 copies/mL
Dolutegravir plus Lamivudine as Initial Dual Therapy
PADDLE: Baseline Characteristics
Source: Cahn P, et al. J Int AIDS Soc. 2017;20:1-7.
Demographic and
Baseline CharacteristicsDolutegravir + Lamivudine
(n = 20)
Age (years), median 34 years
Male 19 (95%)
Mode of Transmission
MSM
Heterosexual
15 (75%)
5 (25%)
HIV RNA (copies/mL), median 24,128
CD4 count (cells/mm3), median 507
Dolutegravir plus Lamivudine as Initial Dual Therapy
PADDLE: Results
Week 48 Virologic Response (by FDA Snapshot Analysis)
Source: Cahn P, et al. J Int AIDS Soc. 2017;20:1-7.
90
0
20
40
60
80
100
HIV
RN
A <
50 c
op
ies
/mL
(%
)
*Other 2 participants:
- 1 committed suicide during study
- 1 developed virologic failure with HIV RNA = 99 copies/mL at week 36 and 246 copies/mL at week 39;
patient had HIV RNA <50 copies/mL at week 48 (baseline HIV RNA = 106,320 copies/mL)
18/20*
Dolutegravir plus Lamivudine as Initial Dual Therapy
PADDLE: Conclusion
Source: Cahn P, et al. J Int AIDS Soc. 2017;20:1-7.
Conclusion: “This novel dual regimen of dolutegravir and lamivudine
warrants further clinical research and consideration as a potential
therapeutic option for ARV-therapy-naive patients.”
DTG + 3TC for Initial ART
ACTG 5353
Dolutegravir plus Lamivudine for Initial ART
ACTG 5353: Background
Source: Nyaku AN, et al. J Antimicrob Chemother. 2019;74:1376-80.
Study Design: ACTG 5353
• Background:
- Phase II, single-arm, pilot study to
assess virologic efficacy of
dolutegravir plus lamivudine as initial
2-drug antiretroviral therapy
• Enrollment Criteria:
- Antiretroviral-naïve adults
- HIV RNA ≥1,000 copies/mL and
<500,000 copies/mL
- No evidence of NRTI, integrase, or
major PI resistance mutations
- No chronic HBV infection
Dolutegravir + Lamivudine(n = 120)
24 weeks
n = 83 with HIV RNA ≤100,000 copies/mL
n = 37 with HIV RNA >100,000 copies/mL
Dolutegravir plus Lamivudine for Initial ART
ACTG 5353: Baseline Characteristics
Source: Nyaku AN, et al. J Antimicrob Chemother. 2019;74:1376-80.
ACTG 5353: Baseline Characteristics
CharacteristicOverall Study Population
(n =120)
Age, years, median (IQR) 30 (24-41)
Male, % 87
Black or African American, % 40
Latino, % 27
CD4 count, cells/mm3, median (IQR) 387 (288-596)
HIV RNA, log10 copies/mL, median (IQR) 4.61 (3.94-5.05)
Dolutegravir plus Lamivudine for Initial ART
ACTG 5353: Results
Week 48 Virologic Response (Intention-to-Treat Analysis)
Source: Nyaku AN, et al. J Antimicrob Chemother. 2019;74:1376-80.
85 88
78
0
20
40
60
80
100
All ≤100,000 copies/mL >100,000 copies/mL
HIV
RN
A <
50 c
op
ies
/mL
(%
)
Baseline HIV RNA
1 participant with virologic failure by week 24 had M184V and R263R/K detected
No virologic failure with resistance occurred between week 24 and week 48
Dolutegravir plus Lamivudine for Initial ART
ACTG 5353: Results
Source: Nyaku AN, et al. J Antimicrob Chemother. 2019;74:1376-80.
ACTG 5353 Virologic Results
ResultTotal
(n=120)
Baseline HIV
RNA ≤100,000
(n=83)
Baseline HIV
RNA >100,000
(n=37)
Virologic success,
HIV RNA <50 copies/mL, n (%)102 (85) 73 (88) 29 (78)
Virologic non-success, n (%) 6 (5) 3 (4) 3 (8)
HIV RNA >50 copies/mL 2 1 1
Stopped for lack of efficacy
while HIV RNA >50 copies/mL1 0 1
Stopped for other reasons, HIV
RNA >50 copies/mL 3 2 1
No data in window, n (%) 12 (10) 7 (8) 5 (14)
On study but missing data in
window3 0 3
Stopped for other reasons
(LTFU, pregnancy)9 7 2
Dolutegravir plus Lamivudine for Initial ART
ACTG 5353: Conclusion
Source: Nyaku AN, et al. J Antimicrob Chemother. 2019;74:1376-80.
Conclusion: “These results add to the evidence that
dolutegravir plus lamivudine is a safe and effective option for
initial ART in individuals with HIV-1 RNA <500,000
copies/mL.”
Dolutegravir-Lamivudine
SWITCH STUDIES
Switch to DTG/3TC vs Continued TAF-Based 3-Drug ART
TANGO
Switch to DTG/3TC vs Continued TAF-Based 3-Drug ART
TANGO: Background
Source: van Wyk J, et al. Clin Infect Dis. 2020. Jan 6. [Epub ahead of print]
Study Design: TANGO
• Background:
- Ongoing, phase 3, randomized, open
label, multicenter, non-inferiority trial
comparing switching to 2-drug DTG-3TC
versus remaining on 3- or 4-drug TAF-
based regimen
• Enrollment Criteria:
- Age ≥18 years
- HIV RNA <50 copies/mL for >6 months
- Taking 3- or 4-drug TAF-based ART
- TDF to TAF switch allowed if ≥3 months
before screening
- No HBV or need for HCV treatment
- No prior virologic failure
- No prior NRTI or INSTI resistance
Switch Regimen
Dolutegravir-Lamivudine
(2 Active Drugs)n = 369
Maintain Regimen
TAF-Based Regimen
(3 Active Drugs)n = 372
Primary endpoint: virologic response
at 48 weeks by FDA snapshot
Switch to DTG/3TC vs Continued TAF-Based 3-Drug ART
TANGO: Baseline Characteristics
Source: van Wyk J, et al. Clin Infect Dis. 2020. Jan 6. [Epub ahead of print]
• Source: Cahn P et al. Lancet. 2019;393(10167):143-155CharacteristicDTG/3TC(n = 369)
TAF-Based ART(n = 372)
Age, years, median (range) 40 (20-74) 39 (18-73)
Female, n (%) 25 (7) 33 (9)
White, n (%) 297 (81) 289 (78)
African American/African, n (%) 50 (14) 58 (16)
CD4 cell count <500, n (%) 98 (27) 74 (20)
CD4 cell count ≥500, n (%) 271 (73) 298 (80)
Months on ART, median (range) 33.8 (7.1-201.2) 35.1 (7.0-160.8)
Baseline third agent class
INSTI 289 (78) 296 (80)
NNRTI 51 (14) 48 (13)
PI 29 (8) 28 (8)
Switch to DTG/3TC vs Continued TAF-Based 3-Drug ART
TANGO: Results
Week 48 Virologic Response (Intention-to-Treat Analysis)
Source: van Wyk J, et al. Clin Infect Dis. 2020. Jan 6. [Epub ahead of print]
93 93
0
20
40
60
80
100
HIV
RN
A <
50 c
op
ies
/mL
(%
)
Dolutegravir-Lamivudine TAF-Based ART
• Confirmed withdrawal for virologic failure: 0 in DTG/3TC arm, 1 in TAF-based ART arm
• No new resistance mutations occurred
• 4 with baseline M184V/I in DTG/3TC arm (by proviral genotype) suppressed at week 48
Switch to DTG/3TC vs Continued TAF-Based 3-Drug ART
TANGO: Results
Week 48 Changes in Renal Function (Plasma/Serum Markers)
Source: van Wyk J, et al. Clin Infect Dis. 2020. Jan 6. [Epub ahead of print]
6.7
-7.7
0.12.2
-3.0-1.6
-15
-10
-5
0
5
10
15
Creatinine* GFR by creatinine* GFR by cystatin C
Ad
jus
ted
mea
n c
han
ge
fro
m
ba
se
lin
e
Dolutegravir-Lamivudine TAF-Based ART
*Statistically significant difference
Switch to DTG/3TC vs Continued TAF-Based 3-Drug ART
TANGO: Results
Week 48 Changes in Markers of Proximal Tubulopathy (Urine Tests)
Source: van Wyk J, et al. Clin Infect Dis. 2020. Jan 6. [Epub ahead of print]
-2.9
6.3
-2.7
1.6
6.7
-7.8-10.0
-7.5
-5.0
-2.5
0.0
2.5
5.0
7.5
10.0
Protein toCreatinine (g/mol)
Retinol-binding protein toCreatinine (ug/mmol)
Beta-2 microglobulin tocreatinine (mg/mmol)
Ch
an
ge f
rom
baselin
e,
%
Dolutegravir-Lamivudine TAF-Based ART
Switch to DTG/3TC vs Continued TAF-Based 3-Drug ART
TANGO: Conclusions
Source: van Wyk J, et al. Clin Infect Dis. 2020. Jan 6. [Epub ahead of print]
Conclusion: “The 2-drug regimen dolutegravir-lamivudine was non-
inferior in maintaining virologic suppression vs a tenofovir alafenamide-
based regimen at Week 48, with no virologic failure or emergent
resistance reported in the dolutegravir-lamivudinegroup, supporting its
use as a simplification strategy for virologically suppressed people living
with HIV-1.”
Dolutegravir + Lamivudine as Maintenance Dual Therapy
LAMIDOL
Dolutegravir plus Lamivudine as Maintenance Dual Therapy
LAMIDOL: Design
Source: Joly V, et al. J Antimicrob Chemother. 2019;74:739-45.
Study Design: LAMIDOL
• Background: Non-comparative, open-label,
single-arm, multicenter trial to evaluate the
efficacy and tolerance of once daily
dolutegravir plus lamivudine as
maintenance dual therapy
• Inclusion Criteria:
- Age ≥18 years
- Nadir CD4 count >200 cells/mm3
- HIV RNA <50 copies/mL for ≥2 years
- Wild-type baseline genotype
- First-line 3-drug ART:
2 NRTI’s + NNRTI, boosted PI, or INSTI
- Prior modifications for intolerance or
simplification allowed
- No HBV co-infection
• Regimen (Once daily)
- Dolutegravir 50 mg + Lamivudine 300 mg
Dolutegravir
+ Lamivudine(n = 104)
*Phase 1: third agent switched to dolutegravir
*Phase 1 **Phase 2
8 weeks
**Phase 2: 2NRTIs switched to lamivudine
Dolutegravir
+ 2 NRTI’s(n = 110)
40 weeks
Dolutegravir plus Lamivudine as Maintenance Dual Therapy
LAMIDOL: Baseline Characteristics
Source: Joly V, et al. J Antimicrob Chemother. 2019;74:739-45.
Participants who Entered Phase 2Dolutegravir-Lamivudine
n = 104
Age (median) 45 years
Male 89 (85.6%)
MSM 73 (70.2%)
Duration since HIV diagnosis (median) 6.3 years
Time on current ART (median) 4.0 years
Nadir CD4 count (median) 399 cells/mm3
Current CD4 count (median) 743 cells/mm3
Baseline NNRTI 58 (55.8%)
Baseline PI 24 (23.1%)
Baseline INSTI 22 (21.2%)
Dolutegravir plus Lamivudine as Maintenance Dual Therapy
LAMIDOL: Results
Week 48 Virologic Response (by FDA Snapshot Analysis)
Source: Joly V, et al. J Antimicrob Chemother. 2019;74:739-45.
97
0
20
40
60
80
100
HIV
RN
A <
50 c
op
ies
/mL
(%
)
*Other 3 participants:
- 1 with low-level viremia (resuppressed with 3-drug antiretroviral therapy),
- 1 treatment modification decided by investigator, and
- 1 lost to follow-up
101/104*
Dolutegravir plus Lamivudine as Maintenance Dual Therapy
LAMIDOL: Conclusion
Source: Joly V, et al. J Antimicrob Chemother. 2019;74:739-45.
Conclusion: “Dolutegravir plus lamivudine is a promising maintenance
therapy in HIV-1-infected patients with controlled virological
suppression.”
DTG + 3TC Maintenance ART vs. Continued 3-Drug ART
ASPIRE
DTG + 3TC Maintenance ART vs Continued 3-Drug ART
ASPIRE: Background
Source: Taiwo B, et al. Clin Infect Dis. 2018;66:1794-7.
Study Design: ASPIRE
• Background:
- Open-label, multicenter, pilot randomized
trial that enrolled persons with suppressed
HIV RNA levels and compared switch to 2-
drug regimen versus continuing standard 3-
drug antiretroviral therapy
• Inclusion Criteria:
- Adults living with HIV
- HIV RNA <50 copies/mL ≥2x over 48 weeks
- Screening HIV RNA <20 copies/mL
- Taking any 3-drug ART regimen
- No history of virologic failure
- No known NRTI or INSTI mutations
- No chronic HBV
- CrCl ≥50 mL/min
Dolutegravir + Lamivudine(n = 44)
Continue 3-drug ART(n = 45)
DTG + 3TC Maintenance ART vs Continued 3-Drug ART
ASPIRE: Baseline Characteristics
Source: Taiwo B, et al. Clin Infect Dis. 2018;66:1794-7.
ASPIRE: Baseline Characteristics
CharacteristicOverall Study Population
(n = 89)
Age, years, median (IQR) 47 (38-54)
Male, % 88
White, % 60
Black or African American, % 38
Hispanic ethnicity, % 15
CD4 count, cells/mm3, median (IQR) 680 (498-927)
Time on ART, years, median (IQR) 5.7 (3.7-7.5)
Pre-randomization INSTI, % 37
Pre-randomization PI, % 33
Pre-randomization NNRTI, % 30
93 9191 89
0
20
40
60
80
100
24 weeks 48 weeks
HIV
RN
A <
50 c
op
ies
/mL
(%
)
Dolutegravir + Lamivudine 3-Drug Antiretroviral Therapy
DTG + 3TC Maintenance ART vs Continued 3-Drug ART
ASPIRE: Results
Week 24 & 48 Virologic Responses (Intention-to-Treat Analysis)
Source: Taiwo B, et al. Clin Infect Dis. 2018;66:1794-7.
One virologic failure occurred in the dolutegravir + lamivudine arm; no resistance mutations detected
41/44 41/45 40/44 40/45
DTG + 3TC Maintenance ART vs Continued 3-Drug ART
ASPIRE: Conclusion
Source: Taiwo B, et al. Clin Infect Dis. 2018;66:1794-7.
Conclusion: “In this randomized pilot clinical trial, dolutegravir plus lamivudine
was noninferior to continuation of standard 3-drug maintenance antiretroviral
therapy. There was no emergence of drug resistance in the participant who
experienced virologic failure while receiving dolutegravir plus lamivudine.”
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.