For treatment-naïve and virologically suppressed adults with HIV-1. See Full Indication.
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.
TRIAL DESIGN
Studied in 2 Robust Phase 3 Clinical Trials1,2
GEMINI 1 & 2 (pooled)
- Two ongoing, identically designed, Phase 3, randomized, parallel-group, noninferiority trials in 1433 treatment-naïve adult participants (pooled data)*
Double blind through 96 weeks. Open-label phase from 96 weeks to 144 weeks.
Participants received 1 dolutegravir 50-mg tablet and 1 lamivudine 300-mg tablet once daily.
Inclusion Criteria:
- Treatment naïve
- ≥18 years old
- HIV-1 RNA 1000 copies/mL to ≤500,000 copies/mL at screening
- CrCl ≥50 mL/min
- No severe hepatic impairment (Child-Pugh Class C)
- HBV negative
- No evidence of major resistance-associated mutations (<1% of screened participants had an M184V/I mutation at baseline and were excluded)2
Primary Endpoint (GEMINI 1 & 2)
- The proportion of participants 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
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.
EFFICACY
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.
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.
RESISTANCE RESULTS
As a prespecified secondary endpoint, participants 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.
A High Barrier to Resistance Through 144 Weeks in Treatment-Naïve Adults4
||1 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).
CVW=confirmed virologic withdrawal; 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 at Week 144
Bone Turnover Markers in GEMINI 1 & 2 Pooled Analysis4
ADJUSTED MEAN CHANGE FROM BASELINE (µg/L) THROUGH WEEK 144 (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.4
BMI=body mass index.
Change From Baseline in Renal Biomarkers With DOVATO vs a TDF-Containing Regimen at Week 144
Urine Renal Biomarkers in GEMINI 1 & 2 Pooled Analysis4
URINE RENAL BIOMARKERS: CHANGE FROM BASELINE THROUGH WEEK 144, % (PRESPECIFIED SECONDARY ENDPOINT)#
Change from baseline to Week 144 in serum creatinine4#
The clinical significance is unknown.
#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. Estimated from geometric mean ratios for baseline and Week 144. Based on the same model as plasma/serum markers except adjusting for loge-transformed baseline biomarker.
Change From Baseline in Serum Creatinine at Week 1482
- The adjusted mean change in serum creatinine from baseline to Week 148 in participants randomized to DOVATO (n=571) and DTG+TDF/FTC (n=546) was 0.147 mg/dL vs 0.179 mg/dL
- 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
References:
- 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. doi: 10.1016/S0140-6736(18)32462-0
- Data on file, ViiV Healthcare.
- Cahn P, Madero JS, Arribas JR, et al. Durable efficacy of dolutegravir plus lamivudine in antiretroviral treatment-naive 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. Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy-naive adults with HIV-1 infection. AIDS. 2021; Sept 15. doi: 10.1097/QAD.0000000000003070
You May Also Be Interested In
DLLWCNT220004
