The clinical trials for DOVATO—GEMINI 1 & 2—were performed at 192 centers in 21 countries. The primary objective of the studies was to evaluate the efficacy and safety of DOVATO, a two-drug regimen, compared with the three-drug regimen of DTG + TDF/FTC for treatment of HIV-1 infection in ART-naïve adults. Healthcare professionals are encouraged to explore the results in detail by accessing the information below.
Studied in 2 Robust Phase 3 Clinical Trials1
GEMINI 1 & 2 (pooled)
- Two ongoing, identically designed, Phase 3, randomized, parallel-group, noninferiority trials in 1433 treatment-naïve adult patients (pooled data)*
Double blind through 96 weeks. Open-label phase from 96 weeks to 144 weeks.
Patients received 1 dolutegravir 50-mg tablet and 1 lamivudine 300-mg tablet once daily.
- Treatment naïve
- ≥18 years old
- HIV-1 RNA 1000 copies/mL to ≤500,000 copies/mL at screening
- CrCl ≥50 mL/min
- HBV negative
- No evidence of major resistance-associated mutations (<1% of screened patients had a M184V/I mutation at baseline and were excluded)2
Primary Endpoint (GEMINI 1 & 2)
- The proportion of patients with HIV-1 RNA <50 copies/mL at Week 48 using the FDA snapshot analysis with 10% noninferiority margin
ART=antiretroviral therapy; CrCl=creatinine clearance; DTG=dolutegravir; FDA=Food and Drug Administration; FTC=emtricitabine; HBV=hepatitis B virus; TDF=tenofovir disoproxil fumarate.
Pooled Baseline Characteristics From GEMINI 1 & 21
DTG + TDF/FTC
|Median age||32 years||33 years|
|African American or African heritage
|HIV-1 RNA >100,000 copies/mL‡||20%||21%|
|CD4+ T-cell count ≤200 cells/mm3||9%||8%|
|CDC Stage 3 (AIDS)||9%||8%|
2% of participants in each arm had baseline HIV-1 RNA >500,000 copies/mL.
CDC=Centers for Disease Control and Prevention; HCV=hepatitis C virus.
The virologic efficacy of DOVATO has been tested in two Phase 3 clinical trials—GEMINI 1 & 2. Detailed below are primary endpoint results as well as the results from some prespecified secondary endpoints.
GEMINI 1 & 2: 144-Week Efficacy Data
Proven, Sustained Virologic Suppression Through 144 Weeks
GEMINI 1 & 2–DOVATO Was Noninferior to DTG + TDF/FTC at 48, 96, and 144 Weeks
POOLED VIROLOGIC RESPONSE (ITT-E; SNAPSHOT ANALYSIS)1,3,4
CI=confidence interval; ITT–E=intent-to-treat–exposed.
as a DTG-based 3-drug regimen
GEMINI 1 & 2: 96-Week SUBGROUP ANALYSIS
Powerful Results Include Data in High Viral Loads at 96 Weeks
GEMINI 1 & 2—Pooled Virologic Success Rates Stratified by Baseline Viral Load Subgroup at Week 962,3
- HIV-1 RNA ≥50 copies/mL: DOVATO, 3.1%; DTG + TDF/FTC, 2.0%
- No virologic data: DOVATO, 10.9%; DTG + TDF/FTC, 8.5%
Summary of Virologic Outcomes
GEMINI 1 & 2—Pooled Analysis at 96 Weeks2,3
In patients with no virologic data at Week 96, none had last HIV-1 RNA value >50 copies/mL except for 1 patient in the DTG + TDF/FTC group.
Other reasons for discontinuation at Week 96 included protocol deviation, lost to follow-up, physician decision, withdrawal by patient, and lack of efficacy (in 1 patient in the DTG + TDF/FTC group).
GEMINI 1 & 2: 48-Week SUBGROUP ANALYSIS
Powerful Results Include Data in High Viral Loads at 48 Weeks
GEMINI 1 & 2—Pooled Virologic Success Rates Stratified by Baseline Viral Load Subgroup at Week 481
As a prespecified secondary endpoint, patients who met the protocol-defined confirmed virologic withdrawal criteria across the pooled GEMINI-1 and GEMINI-2 trials were tested for emergent INSTI or NRTI substitutions conferring resistance through 144 weeks.
Participant with reported non-adherence to the separate pills of DTG + 3TC developed treatment-emergent resistance: M184V (NRTI) at Week 132 and R263R/K (INSTI) at Week 144; the participant was withdrawn from the study and re-suppressed on a DTG-containing regimen.
Confirmed virologic withdrawal (CVW)—defined as either virologic nonresponse (a decrease in plasma HIV-1 RNA of <1 log10 copies/mL by Week 12, with subsequent confirmation, unless plasma HIV-1 RNA is <200 copies/mL or confirmed plasma HIV-1 RNA ≥200 copies/mL on or after Week 24) or virologic rebound (confirmed rebound in plasma HIV-1 RNA levels to ≥200 copies/mL after prior confirmed suppression to <200 copies/mL).
3TC=lamivudine; INSTI=integrase strand transfer inhibitor; NRTI=nucleoside reverse transcriptase inhibitor.
BONE AND RENAL BIOMARKERS
Change From Baseline in Bone Biomarkers With DOVATO vs a TDF-Containing Regimen
Bone Turnover Markers in GEMINI 1 & 2 Pooled Analysis2,3
ADJUSTED MEAN CHANGE FROM BASELINE (µg/L) THROUGH WEEK 96 (PRESPECIFIED SECONDARY ENDPOINT)**
The clinical significance is unknown.
Adjusted for treatment, baseline plasma HIV-1 RNA, baseline CD4+ T-cell count, age, sex, race, BMI, smoking status, current Vitamin D use, and baseline biomarker value.3
BMI=body mass index.
Change From Baseline in Renal Biomarkers With DOVATO vs a TDF-Containing Regimen
Renal Biomarkers in GEMINI 1 & 2 Pooled Analysis2,3
RENAL BIOMARKERS: CHANGE FROM BASELINE THROUGH WEEK 96, % (PRESPECIFIED SECONDARY ENDPOINT)††
Change from baseline to Week 96 in serum creatinine2,3††
The clinical significance is unknown.
- The adjusted mean change in serum creatinine from baseline to Week 96 in patients randomized to DOVATO (n=716) and DTG+TDF/FTC (n=717) was 0.138 mg/dL vs 0.176 mg/dL, P<0.001
- Dolutegravir has been shown to increase serum creatinine due to inhibition of tubular secretion of creatinine without affecting renal glomerular function. Increases in serum creatinine occurred within the first 4 weeks of treatment in both arms and remained stable through 48 weeks
Adjusted for treatment, baseline plasma HIV-1 RNA, baseline CD4+ T-cell count, age, sex, race, presence of diabetes, presence of hypertension, and baseline biomarker value.
- Cahn P, Sierra Madero J, Arribas J, et al; and GEMINI Study Team. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. Lancet. 2019;393(10167):143-155.
- Data on file, ViiV Healthcare.
- Cahn P, Madero JS, Arribas JR, et al. Durable efficacy of dolutegravir plus lamivudine in antiretroviral treatment-naïve adults with HIV-1 infection: 96-week results from the GEMINI-1 and GEMINI-2 randomized clinical trials. J Acquir Immune Defic Syndr. 2020;83(3):310-318. doi:10.1097/QAI.0000000000002275.
- Cahn P, Madero JS, Arribas JR, et al. Durable efficacy of dolutegravir (DTG) plus lamivudine (3TC) in antiretroviral treatment-naïve adults with HIV-1 infection—3-year results from the GEMINI studies. Presented at: HIV Glasgow 2020; October 5-8, 2020; Virtual. Poster P018.