GEMINI 1 & 2

STUDIED >1400 TREATMENT-NAÏVE ADULTS THROUGH 144 WEEKS

Two men talking and laughing together. Not actual patients.

GEMINI 1 & 2: Studied >1400 Treatment-Naïve Adults Through 144 Weeks1,2

GEMINI 1 & 2 (pooled): Phase 3, Identically Designed, Double-Blind, Noninferiority Trials

GEMINI 1 & 2 pooled study design infographic.

Primary Endpoint

Proportion of participants with HIV-1 RNA <50 copies/mL at Week 48 (by FDA Snapshot algorithm, ITT–E with a 10% noninferiority margin) 

Secondary Endpoint

Proportion of participants with plasma HIV-1 RNA <50 copies/mL at Weeks 96 and 144 (by FDA Snapshot algorithm for the ITT–E with a 10% noninferiority margin)

GEMINI Baseline Characteristics (Pooled)1

 

DOVATO

(N=716), n (%)

DTG + TDF/FTC

(N =717), n (%)
Median age 32 years 33 years
Female 113 (16%) 98 (14%)
African American or African heritage 99 (14%) 76 (11%)
White 480 (67%) 497 (69%)
Asian 71 (10%) 72 (10%)

HIV-1 RNA >100,000 copies/mL*

 140 (20%) 153 (21%)
CD4+ T-cell count ≤200 cells/mm3 63 (9%) 55 (8%)
CDC Stage 3 (AIDS)  66 (9%) 60 (8%)
HCV co-infection 39 (5%)  49 (7%)

20% OF PARTICIPANTS ON DOVATO HAD BASELINE VIRAL LOADS >100,000 COPIES/mL

*2% of participants in each arm had baseline HIV-1 RNA ≥500,000 copies/mL.

Proven, Sustained Virologic Suppression Through 144 Weeks1,3,4

GEMINI 1 & 2—DOVATO Was Noninferior to DTG + TDF/FTC at 48, 96, and 144 Weeks

Pooled Virologic Response (ITT–E; Snapshot analysis)

Chart showing virologic response of primary endpoint of 48 weeks, and secondary endpoints of 96 and 144 weeks.

The evaluation of antiviral activity over time was a prespecified secondary endpoint, ITT–E population.

DOVATO VIROLOGIC SUPPRESSION

•RAPID: 72% at Week 4  •POWERFUL: 91% at Week 48  •DURABLE: 82% at Week 144

Post Hoc Analysis: Participants With HIV-1 RNA <50 copies/mL at Week 144, by Adherence Category5†

Participants were stratified by ≥90% vs <90% adherence

Chart showing HIV-1 RNA copies results comparing DOVATO with DTG plus TDF slash FTC at end of clinical trial.

Methods

  • Association between adherence and virologic suppression was evaluated at Week 144 using FDA Snapshot
  • Adherence (%) was calculated as the number of pills taken (pills returned subtracted from pills available) per number of pills prescribed, estimated using pill count data

FDA Snapshot Treatment Difference

  • ≥90% adherence: –2.6% (95% CI; –7.9%, 2.7%); <90% adherence: 1.8% (95% CI; –21.5%, 25.9%)

Limitations

  • Small number of participants in the lower adherence subgroup (5% in both arms)
  • Utilizing pill count to accurately measure adherence
  • Increase in number of patients with no virologic data since Week 48 due to COVID-19

†Results from post hoc analysis are descriptive only.

High Barrier to Resistance Through 144 Weeks in Treatment-Naïve Adults3

 

CVW‡

(cumulative)

All Partipants With

Treatment-Emergent Mutations

DOVATO

(N=716)

 12 1§

DTG + TDF/FTC

(N=716)

 9
 0

‡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).1

§1/716 in the DOVATO arm developed treatment-emergent resistance (M184V at Week 132 and R263R/K at Week 144). In the DTG + TDF/FTC arm, there were no resistance mutations observed among participants.3

In 12 Cases of Confirmed Virologic Withdrawal, Viral Rebound Did Not Lead to Resistance2

Icon of the number zero.

participants had treatment-emergent INSTI or NRTI substitutions conferring resistance through 144 weeks

EXPLORE THE PERFORMANCE OF DOVATO IN A TEST-AND-TREAT SETTING

CONTINUE

Cl=confidence interval; CrCl=creatinine clearance; CVW=confirmed virologic withdrawal; DTG=dolutegravir; FTC=emtricitabine; HBV=hepatitis B virus; HCV=hepatitis C virus; INSTI=integrase strand transfer inhibitor; ITT–E=intent-to-treat–exposed; NRTI=nucleoside reverse transcriptase inhibitor; TDF=tenofovir disoproxil fumarate.

References:

1. Cahn P, Madero JS, Arribas JR, et al; 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

2. Data on file, ViiV Healthcare.

3. Cahn P, Madero JS, Arribas JR, et al. Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy-naïve adults with HIV-1 infection. AIDS. 2022;36(1):39-48. doi:10.1097/QAD.0000000000003070

4. 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

5. Fernvik E, Madero JS, Espinosa N, et al. Impact of treatment adherence on efficacy of DTG + 3TC and DTG + TDF/FTC: pooled week 144 analysis of the GEMINI-1 and GEMINI-2 clinical studies. Presented at: 18th European AIDS Conference; October 27–30, 2021; Virtual. Poster PE2/63.

PMUS-DLLWCNT240064 October 2024