For treatment-naïve and virologically suppressed adults with HIV-1. See Full Indication.

TREATMENT-NAÏVE
CLINICAL TRIALS

TREATMENT-NAÏVE
CLINICAL TRIALS

GEMINI CLINICAL TRIALS

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.

TRIAL DESIGN

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)*

Open label phase from 96 weeks to 144 weeks.
Patients 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
  • 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

 

DOVATO
(n=716)

DTG + TDF/FTC
(n=717)

Median age 32 years 33 years
Female
16% 14%
African American or African heritage  
14% 11%
White  
67% 69%
Asian   
10% 10%
HIV-1 RNA >100,000 copies/mL 20% 21%
CD4+ T-cell count ≤ 200 cells/mm3     9% 8%
CDC Stage 3 (AIDS) 9% 8%
HCV co-infection 5% 7%

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, such as the evaluation of antiviral activity over time in the ITT-E population.

Delivers the Power of a DTG-Based 3-Drug Regimen at 48 Weeks With Rapid and Sustained Virologic Suppression

Primary Endpoint Results Noninferior to DTG + TDF/FTC at Week 481,2

GEMINI 1 & 2—POOLED VIROLOGIC RESPONSE BY VISIT (ITT-E; SNAPSHOT ANALYSIS)

AS EFFECTIVE
as a DTG-based 3-drug regimen

CI=confidence interval; ITT-E=intent-to-treat–exposed.

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

Subgroup analysis by baseline viral load was a prespecified secondary endpoint, ITT-E population.

Powerful Results With Durable Virologic Suppression at 96 Weeks

Prespecified Secondary Endpoint—Noninferior to DTG + TDF/FTC at 96 Weeks2,3

GEMINI 1 & 2—Pooled Virologic Response (ITT-E; snapshot 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

 

Subgroup analysis by baseline viral load was a prespecified secondary endpoint, ITT-E population.

 

  • 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).

RESISTANCE RESULTS

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 96 weeks.

Zero Resistance Through 96 Weeks2,3¶

High Barrier to Resistance Supported By 96-Week Data

  • Confirmed virologic withdrawal# occurred in 11 patients taking DOVATO and 7 patients taking DTG + TDF/FTC
  • Of the patients with confirmed virologic withdrawal taking DOVATO, none had treatment-emergent INSTI or NRTI resistance substitutions through 96 weeks

Based on a pooled analysis from GEMINI 1 & 2.
Confirmed virologic withdrawal—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 levels >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).2,3

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 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.

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.

References:

  1. 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.
  2. Data on file, ViiV Healthcare.
  3. 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.

DLLWCNT200020